Premature chromosome condensation in human leukemia.

Premature chromosome condensation (PCC) has previously been observed in tissue culture and is believed to arise from asynchronous mitotic activity in multinucleated cells in which the affected nucleus is in interphase and at least one nucleus is in metaphase. Such cells have been noted following fusion induced by virus infection, spontaneously, and after treatment with cytochalasin B. The phenomenon has also been observed in malignant pleural effusions, but has not previously been described as a feature of hematologic disease. In this study, we report the observations of PCC in seven patients. Six of these patients had either acute myeloblastic leukemia or acute myelomonoblastic leukemia in association with the features of erythroleukemia, i.e., leukoerythroblastic reaction in the blood, and erythroid multinuclearity, "megaloblastoid" changes, and PAS-positive staining of erythroid precursor cells in the bone marrow. In all patients, erythroid multinuclearity has been noted. However, not all patients with erythroleukemia exhibit PCC. In this series, three additional patients have had similar bone marrow morphologic changes without PCC. The finding of PCC in erythroleukemia may have important implications as to etiology of this disorder.


Trisomy 8 in the bone marrow associated with high red cell glutathione reductase activity.

In a series of 841 patients with hematologic disorders, 10 individuals were found to have an extra C group chromosome in their bone marrow cells. In two the extra chromosome was not identified, but in the remaining eight it was No. 8. Four of these ten patients had leukemia, and the others had cytopenias or other probably preleukemic conditions. The mean value for glutathione reductase activity in the red cells of four patients with trisomy 8 was significantly higher (2980 +/- 940 mumoles/min/liter of erythrocytes) than in normal controls (1930 +/- 360) or in any of five different control groups of patients with hematologic disorders. The extent of enzyme activation as a result of preincubation with exogenous flavin adenine dinucleotide was similar in the erythrocytes of all groups. The reasons for the high values of red cell glutathione reductase activity in patients with trisomy 8 are discussed in the light of the proposed assignment of the gene for that enzyme to chromosome 8.


Cyclophosphamide-asparaginase- vincristine-prednisone induction therapy in childhood acute lymphocytic and nonlymphocytic leukemia.

A remission-induction regimen for childhood leukemia using cyclophosphamide, asparaginase, vincristine, and prednisone (CAVP) was compared to standard vincristine-prednisone (VP) induction. The more intensive regimen was associated with a lower complete remission rate (81% vs 93%) and a higher early death rate from infection (15% vs 5%) for acute lymphocytic leukemia. In contrast, complete remission was achieved in 58% of children with acute nonlymphocytic leukemia treated with CAVP compared to 18% for VP. Early death rates were similar (27% vs 25%). These observations corroborate previous studies in childhood nonlymphocytic leukemia showing activity for asparaginase. Preliminary analysis of remission duration and survival for responders shows no advantage for those who survived the more intensive induction.


[Experimental production of bone sarcomas in the rabbit by a single local injection of beryllium].

The local intra-osseous injection of double zinc beryllium silicate into the tibial or femoral epiphysis of a rabbit causes an osteogenic sarcoma in 70 p. 100 of cases. These experimental conditions make it possible to reveal early non specific radiological alterations, later on secondary alterations corresponding to the development of the sarcoma and finally to follow the spontaneous evolution of the tumor. Moreover, this experimental process of induction of an osteogenic sarcoma by means of a local intra-osseous injection is vastly better than an intra-venous injection which causes straight-away multiple visceral lesions.


Acute lymphoblastic leukemia in adults and children. Differences in response with similar therapeutic regimens.

Twenty-three adult patients (ages greater than 15 years) and 75 children with acute lymphoblastic leukemia were treated with similar intensive, sequential cytotoxic protocols (L-2). The adult patients have lower remission rate (78%) than the children (98%). The duration of remission and the length of survival are also shorter in adults. The incidence of central nervous system (CNS) relapse in adults (27.7%) is higher than in children (7.1%) suggesting that prolonged prophylactic intrathecal methotrexate as given to the children is more effective than the schedule used for adults where intrathecal methotrexate was given only in the first 2 months of therapy. The low incidence of CNS involvement in children on the L-2 protocol compares favorably with other series reported using a combination of cranial irradiation and intrathecal methotrexate. In both adults and children there seemed to be a higher incidence of CNS involvement in patients with initial white blood cell counts greater than 25,000 cells/mm3.


The ultrastructure of osteosarcoma. A review of twenty cases.

The ultrastructural features of 20 cases of osteosarcoma are discussed. Characteristically, the malignant cells (osteoblasts) contained large quantities of dilated, anastomosing rough endoplasmic reticulum, ofter forming large lakes. Mitochondria were sparse. Similar features are seen in osteoblasts in normal developing bone. Marked ultrastructural similarities of cells from chondrosarcomatous, fibrosarcomatous and typical osteosarcomatous areas of these tumors strongly supports the concept that these neoplastic cells all arise from the same progenitor cell. Malignant giant cells were readily differentiated from benign osteoclasts. The most significant ultrastructural findings were the varying degrees of calcification in the intercellular areas (osteoid), ranging from an extensive dense deposition of hydroxyapatite crystals which obscured the underlying collagen fibers, to focal collectors, or puffs, of slender needle-shaped hydroxyapatite crystals deposited on or along collagen fibers. The earliest apparent evidence of calcification was the presence of small electron-dense particles on or in collagen fibers.


The heterogeneity of leukemic reticuloendotheliosis, "hairy cell leukemia". Evidence for its monocytic origin.

The presence of B, T, and monocyte markers were studied on the spleen and peripheral blood mononuclear cells from two patients with leukemic reticuloendotheliosis. A high proportion of cells from both patients bore a receptor for cytophilic antibody, both in suspension and frozen tissue section. Cells in suspension lacked surface immunoglobulins or a receptor for sheep red blood cells. These results favor the evidence that "hairy cells" are monocytic in origin.


Multiple myeloma, acute leukemia, and Hodgkin's disease. Occurrence in three of four family members.

Among a family of four persons, three members each had a separate malignant disease during a 3-year period. The mother and father concurrently had multiple myeloma and Hodgkin's disease, respectively, and less than 3 years later, their only son was found to have acute granulocytic leukemia. No increased incidence of deaths attributed to Hodgkin's disease, acute leukemia, or multiple myeloma was found in the community. No other cause for this cluster of hematologic malignancies could be found.


Recurrent childhood lymphocytic leukemia following cessation of therapy: treatment and response.

A unique population of patients--children who developed recurrent acute lymphocytic leukemia (ALL) following cessation of initial prolonged therapy--was studied. During a 2-year period, 17 such children were admitted to a planned combination chemotherapy program. Complete bone-marrow remissions were achieved in 16 patients, and the median duration of second hematologic remissions was 216 days. These responses were significantly better than those obtained in seven patients who relapsed during the administration of continuation chemotherapy. Although the rate and duration of induced remissions were notably high, 9 of the 17 patients who relapsed off therapy have again developed recurrent leukemia. This result, together with the moderate toxicity encountered during treatment, indicates that more therapy is needed. The equal proportion of bone marrow and meningeal relapses was interpreted to mean that a secon course of preventive central nervous system therapy early in remission may be especially useful.


Granulocytic sarcoma: local presentation of a systemic disease.

The case of a pregnant woman with a breast mass that proved to be a granulocytic sarcoma is presented. Her systemic therapy was initiated at a time when her tumor burden was possibly relatively low and a good response to the aggressive combination chemotherapy including Daunomycin was obtained. She was successfully carried through pregnancy and delivered a normal child despite combination chemotherapy. Factors relating to her case have been reviewed in the literature.


Chromosomal mosaicism associated with prolonged remission in chronic myelogenous leukemia.

The nature of the relationship between normal stem cells and the leukemic cells of chronic myelogenous leukemia (CML) is of considerable theoretical and practical importance. We studied a patient with CML who has maintained a complete hematologic remission for eight years without therapy. Presently, the only documentable abnormality is mosaicism for the Philadelphia (Ph1) chromosome. Studies of his bone marrow in vitro revealed normal colony formation in agar and normal cellular proliferation and differentiation in liquid culture. Observations in this patient indicate that a Ph1-positive clone may coexist with normal stem cells during prolonged remission in CML and the Ph1-positive cells may not always have a growth advantage over normal cells. The culture studies further suggest that the diminished proliferative capacity of the leukemic cells was not due to in vivo host suppressive factors.


Pseudomalignant osteoblastoma versus arrested osteosarcoma: a case report.

A case is presented which is interpreted as a histologically pseudomalignant osteoblastoma. This diagnosis is supported by the clinical and radiologic findings. Arguments are presented in support of this diagnosis as against an osteogenic sarcoma with an arrest in growth, although this latter diagnosis cannot be completely excluded.


C-G translocation in acute myelocytic leukemia with low neutrophil alkaline phosphatase activity.

A consistent chromosome abnormality of C-G translocation, t(8;21)(q22;q22), was found in 15 acute myelocytic leukemia (AML) patients with low neutrophil alkaline phosphatase (N-AP) activity. Granulocytes of these patients also had specific morphologic abnormalities. The bone marrow showed a tendency to relatively good maturation of leukemic cells for the disease AML. Clinical courses of the patients were mild and median survival was longer than that of patients with normal or high N-AP activity (p = 0.065, suggestive difference). Three out of six male patients with these type of AML had missing Y chromosome in addition to C-G translocation. The results suggest that specific cytogenetic abnormality of C-G translocation would be significantly associated with AML. Contrasting with low N-AP activity and the Philadelphia chromosome in chronic myelocytic leukemia, the findings in AML may offer additional evidence towards the possible relations between alkaline phosphatase activity and C or G chromosome.


Periosteal osteogenic sarcoma.

A study of 102 osteogenic sarcomas of the bone surface revealed that 79 were parosteal osteogenic sarcomas. Roentgenographically, these 79 were dense, lobulated lesions attached by a broad base to underlying bone, usually the lower femoral shaft. Histologically, they were low-grade osteosarcomas. The other 23 lesions (periosteal osteogenic sarcoma) usually involved the upper tibial shaft and presented as small radiolucent lesions on the surface, with formation of spicules of bone perpendicular to the bone shaft. Histologically, these 23 were relatively high-grade, predominantly chondroblastic osteogenic sarcomas. Thirteen of the 23 patients were males, and most were in the second decade of life. Of five patients who had excision of the tumor, two had recurrence. Seven of 13 patients who underwent amputation initially were alive without disease at last follow-up. Only 4 of the 23 patients have dies of metastatic disease.


Parosteal osteogenic sarcoma.

A clinicopathologic study of 79 patients with parosteal osteogenic sarcoma revealed that more females than males were affected and that most of the patients were in the second to the fourth decades of life. Sixty-eight percent of the patients had involvement of the posterior aspect of the lower femoral shaft. The roentgenogram characteristically showed a large, dense lobulated mass attached by a broad base to the underlying bone but with no involvement of bone itself. Microscopically, the tumor presented as well-formed bands of osteoid within a hypocellular spindle cell stroma. Seven of the lesions had foci of high-grade osteogenic sarcoma within an otherwise typical parosteal osteogenic sarcoma. Six of the 79 lesions showed involvement of the medullary cavity at surgery. Thirty-one patients had excision as their initial treatment; four of the 31 required nv further therapy. Ten patients had resection initially; three of the ten had recurrence. Only four of 27 patients who underwent amputation initially developed pulmonary metastasis. The presence of histologically "active" tumor and medullary involvement seemed to affect the prognosis adversely. Our data indicate that complete radical removal of the tumor is the treatment of choice, with resection when feasible and amputation when necessary.


Prognostic value of chromosomal findings in Ph1-positive chronic myelocytic leukemia.

Chromosome examinations were performed on bone marrows from 88 patients with Ph1-positive chronic myelocytic leukemia (CML). As a group, Ph1-positive CML patients with some cytogenetically normal cells in the marrow survived much longer than those whithout such cells in their marrow. The survival for patients whose first bone marrow exhibited only metaphases with a Ph1 and other karyotypic abnormalities was significantly shorter than that for patients whose marrow exhibited only metaphases with a Ph1 and an otherwise normal karyotype or patients whose marrow contained both categories of cells. The shorter the interval between the diagnosis of CML and the first chromosome examination, the greater the frequency of karyotypically normal cells in the bone marrow. Karyotypic progression in CML was a common phenomenon, whereas a reversion was very rare. On the basis of the findings obtained, the early diagnosis and treatment of CML are indicated, both possibly being helped by the chromosomal findings in the marrow. Furthermore, a combination of the chromosomal data and the marrow cell differential may serve as an important prognostic index in CML.


Concanavalin A-induced agglutination of human leukemic and lymphoma cells.

With a newly developed turbidometric method, concanavalin A was shown to agglutinate normal lymphocytes, lymphoma cells, and leukemic cells from chronic lymphocytic leukemia and from acute myelocytic and lymphocytic leukemia. However, there was a marked difference in the kinetics of this agglutination process. Leukemic blast cells and cells from a patient with convoluted lymphoma agglutinated poorly in this system. Conversely, the degree of agglutination for chronic lymphocytic leukemia cells was greater than that for the blast cells and also slightly greater than that for normal lymphocytes. Cultured cells from a Burkitt's lymphoma (Raji) and from a patient with poorly differentiated lymphoma agglutinated very rapidly with concanavalin A. Prior incubation of all cell types with neuraminidase markedly enhanced the agglutination process similar to that of trypsinization. Thus, these studies illustrate the usefulness of this method in quantitating the kinetics of agglutination of various human neoplastic cell types by concanavalin A.


Disposition of [3H]actinomycin D in tumor-bearing mice.

A single, nonlethal dose of actinomycin D will cause total regression and cure of Ridgway osteogenic sarcoma in mice. A cure is not obtained with a single dose daily for 7 days, a dose regimen which kills 10% of normal C57BL/6 X DBA/2 mice. This suggests that actinomycin D is more effective on a single high-dose schedule than on chronic daily therapy. Analysis of drug exposure in Ridgway osteogenic sarcoma and normal mouse tissues following the single and multiple-dose regimens suggests the difference in therapeutic response is due to drug exposure at a higher concentration in Ridgway osteogenic sarcoma after the single high dose than after the multiple-dose regimen. This may be related to the higher drug concentration attained in blood following the single-dose regimen than is attained with the multidose regimen.


Amino acid metabolism of platelets in leukemia.

Platelets from patients with acute myelogenous leukemia, both before and after remission induction, were evaluated for their ability to incorporate D-[U-14C]glucose into the four amino acids, glutamine, asparagine, glutamic acid, and aspartic acid. Normal platelets incorporated about 80% of the activity into the amides, glutamine and asparagine, and only 20% into their respective amino acids, glutamic acid and aspartic acid. Platelets from patients with acute myelogenous leukemia in the acute stage showed a reversal of this pattern, which then returned to normal during remission. However, the concentration of amino acids was higher than normal, suggesting that remission platelets behaved like a young cell population. The abnormal pattern of labeling could be interpreted as a defect in the platelet citric acid cycle thereby compromising its energy source.


Treatment of acute lymphocytic leukemia by high-dose intravenous methotrexate.

A pharmacokinetic study of methotrexate levels in blood and cerebrospinal fluid was performed in 42 patients who received one or more courses of high-dose methotrexate at 500 mg/sq m infused i.v. over a 24-hr period. Methotrexate level in the lumbar cerebrospinal fluid reached 1.2 x 10(-7) M at 0.5 hr and remained constant at that level for the 1st 24 hr. Similar methotrexate levels were noted in the ventricular fluid obtained through an Ommaya device on three patients with brain tumors treated with high doses of methotrexate. Preliminary clinical results using high-dose methotrexate combined with simultaneous intrathecal methotrexate in 23 children with newly diagnosed acute lymphocytic leukemia indicate that this treatment program is safe to administer and to date appears effective in the prevention of central nervous system leukemia.


Patterned relationships between IgM and blast cells in peripheral blood in a child with acute leukemia.

1. Serum IgM determinations and blast cell counts were performed at regular frequent intervals in a case of acute lymphoblastic leukemia in a child. 2. An inverse relationship tended to exist between the concentration of IgM in serum and blast cells in blood during the course of relapses and remissions. 3. High dosage immunosuppressive chemotherapy caused a marked reduction in serum IgM. 4. A relationship appears to exist between IgM and blast cells which may support the concept that impaired ability to produce antibody to leukemia antigens may be an intrinsic component of this disease.


Reactivity of antibody in acute myeloid leukaemia with proliferation-associated nuclear antigen(s).

A reaction between antibody in leukaemic sera and nuclear antigen present in leukaemic cells was detected by means of an anticomplement immunofluorescence test. The antibody was found mainly in patients with myeloid leukaemia, particularly those with a high percentage of blast cells in their peripheral blood. The nuclear antigen(s), however, was present in various proportions of the circulating cells of almost all patients with leukaemia, lymphoma or infectious mononucleosis, as well as in phytohaemagglutinin-transformed blasts and proliferating cell lines. Thus, antibody appeared to be detecting a nuclear component associated with cell proliferation.


Childhood acute lymphocytic leukemia.

Childhood ALL is a potentially curable disease. All children suffering from this ailment should be given an opportunity to live by receiving therapy aimed at permanent cure. The disease requires extensive, complex, and costly diagnostic study and treatment. Specialized care is more efficiently given in centers dedicated to treating patients with malignant diseases. The referring physicians are an essential part of the working team delivering care to the children with acute leukemia. Despite improved results, a significant number of patients fail to develop permanent remission. The risk of relapse after cessation of therapy is greatest in the first year and in patients given no specific CNS therapy. However, modern therapy produces a substantial number of long-term leukemia-free survivals in children with ALL, a majority of which persist after cessation of therapy. After cessation of therapy the quality of survival of the vast majority of patients is excellent.


Drug antagonism and reversibility of the binding of indoleamines in brain.

The specificity of the binding of serotonin to brain preparations was investigated with various competitive agents. A probable relationship between their structure and their capability of displacement was suggested. Bufotenine and morphine displaced serotonin (0.5 X 10(-5) M) binding to synaptic membranes 87 and 49% respectively. Dissociation constants of the binding of 5-HT and tryptamine to synaptic membranes, and displacement constants of certain drugs were determined. The binding of 5-HT and tryptamine to calf brain preparations was also investigated by equilibrium dialysis, in order to determine affinity constants and reversibility of the binding. Differences were noted in the specificity of binding sites for serotonin and tryptamine, suggesting a different binding site for tryptamine. Extrapolations of Scatchard plots were used for determination of the constants. A characteristic low dissociation constant was found for 5-HT in synaptic membranes (K approximately X 10(-6) M). Probably, the binding macromolecule (receptor?) is a proteolipid.


Effect of arabinosyl cytosine on granulopoietic colony formation by marrow cells from leukemic and non-leukemic patients.

This study investigated the arabinosyl cytosine (ara-C) sensitivity of colony formation in culture by human granulopoeitic progenitor cells (CFU-C). Wide variations were observed in the effects of ara-C on CFU-C from the marrow of patients with leukemia in remission after treatment using a chemotherapeutic regimen that included ara-C, or for CFU-C from the marrow of non-leukemic patients. These variations in sensitivity to ara-C could not be attributed to a lack of reproducibility of the culture conditions used, nor to variations in the proliferative state of the CFU-C at the time of exposure to ara-C. No significant correlation was observed between the sensitivity of CFU-C to ara-C and the level of cytidine deaminase in the marrow sample. These results provide some support for the view that cell kill may not be the only basis for the chemotherapeutic effectiveness of ara-C.


Microbial iron chelates with iron donor properties in hemoglobin-synthesizing cells.

Iron incorporation into Friend virus infected leukemic murine spleen cells was studied using the two fungal iron trihydroxamates, fusigen and ferricrocin. Incorporation of 55Fe was measured by isolation of hemoglobin after dimethylsulfoxide-induced hemoglobin synthesis and compared with iron incorporation from 55Fe-labeled ferric citrate.


Gastroesophageal involvement in herpes simplex.

Herpes simplex in the gastric mucosa has not been previously described. The case presented here describes gastritis and esophagitis resulting from herpes simplex in a patient being treated with immunosuppressive agents. These changes were confirmed endoscopically and radiographically. Biopsy specimens of the gastric and esophageal mucosa showed eosinophilic intranuclear inclusion bodies typical of herpes simplex. The pathogenesis and pathological appearance of herpetic gastritis and esophagitis are presented.


[Kleine-Levin syndrome. Female cases and catamneses].

The Kleine-Levin syndrome (periodic hypersomnia and megaphagia in adolescence) was considered till 1962 to be a disorder limited to the male adolescents. Since 1924, however, a few female cases have been reported about. These, being approximately 20 patients, are registered by their essential symptoms together with 2 additional cases observed by the author. Moreover, prospective catamneses, covering periods of more than 12 years, were described for the first time. Probably, the Kleine-Levin-syndrome is the product of disturbed functions involving structures of hypothalamus and the reticular system. The syndrome seems to belong to the same groups of periodical diseases as migraine: in particular it exhibits similar relations to the genital cycle. Therapeutical success was attained by administration of amphetamines. In course of time, the episodes become spontaneously rarer and mostly cease.


Electrolyte concentration in the hypertrophic salivary glands of incisor-amputated rats.

The effect of periodic amputations of the lower incisors of the rat on the electrolyte concentration in the major salivary glands was studied. The incisor amputations caused a hypertrophy of the parotid, submandibular and sublingual glands. The resulting increased weight of the salivary glands was due to a higher dry mass. In general, the electrolyte concentration showed higher values in the salivary gland tissues of the incisor-amputated animals. Considering the parotid, submandibular and sublingual glands respectively, the Na+ concentration was increased by 47%, 50% and 14%; and Mg2+ concentration by 377%, 126+ and 376%. Inorganic phosphorus increased 45% in the parotid, 25% in the subnamdibular and was unchanged in the sublingual gland. K+ concentration increased in the submandibular (12%) and sublingual (100%) glands but decreased in the parotid (24%). The Na+/k+ ratio was higher in the parotid (82%) and submandibular (37%) glands and lower in the sublingual gland (84%). The electrolyte concen-ration changes are discussed in relation to the mechanism and type of stimulation promoted by the incisor-amputations on the major salivary glands of the rat.


[Study of dental fluorosis using an ionic microanalyzer].

Permanent teeth with endemic dental fluorosis, showing mild and moderate mottled enamel, according to the classfication of Dean, were examined with a SMI 300 Cameca ion micro-analyser. In the external third of enamel, abnormally large "sheaths" were disclosed as well as zones characterized by the destruction of prisms. In the dentine, the presence of peritubular dentine rich in Ca, P, FCa, PO, Mg, Na and K has been noted. Hypomineralized spots, poor in these various elements were observed in the intertubular dentine.


Effect of airway diameter, suction catheters, and the bronchofiberscope on airflow in endotracheal and tracheostomy tubes.

Pressure-flow relationships of an artificial airway-mechanical ventilator system were investigated. Endotracheal tubes varying from 7 to 9.5 mm. internal diameter and tracheostomy tubes from 7 to 10 mm. internal diameter were tested over flow-rates from 0.3 to 1.4 L. per second using a tidal volume of 500 ml. The effect of partial obstruction within these airways by suction catheters and the bronchofiberscope was examined. Depending on the internal diameter and the flow-rate, the driving pressure necessary to overcome the resistance of the tubes ranged from 5 to 20 cm. H2O. Partial obstruction of the artificial airways by suction catheters further increased this pressure. The introduction of the bronchofiberscope through an endotracheal tube of 7.5 mm. internal diameter, leaving an effective diameter of 4.9 mm., produced a driving pressure as high as 70 cm. H2O and reduced the flow rate to 50 per cent and the tidal volume to 80 per cent of its set value. Attention should be paid to duration of tracheobronchial suction while the patient is removed from the respirator since a high-grade resistance is created by passage of a suction catheter through an endotracheal tube. Bronchofiberscopy should be cautiously performed through cuffed artificial airways with at least 8 mm. internal diameter because the airway may be too comprised even if mechanical ventilatory assistance is employed.


[Ultrastructural study of human pulp cells cultured in vitro].

Primary cultures from human dental pulp were produced in Leighton tubes in the compound nutritive medium of Eagle consisting of calf serum, ascorbic acid, penicillin and streptomycin. After 2 months, the coverglasses supporting the cultures were recovered and fixed for electron microscopy. The results obtained showed a polarisation of the cells, the presence of a cilium, a highly developed endoplasmic reticulum, a typical Golgi apparatus with coated vesicles in the vicinity, elongated dense secretion vesicles containing a cross-striated filamentous material, numerous mitochondria, microfilaments with thickenings, microtubules, secretion granules, multivesicular bodies and electron dense structures united by a fibre with a periodic cross-striation of 640 A. These cells secreted a collagenous matrix uith an at random fibrillar distribution, fusiform outlines of fibrils (diameters varying from 650 A to 3,600 A), a cross-striation of 640 A and the presence of electron dense zones on the fibrils. "Globules" (with a trilamellar membrane of about 110 A) were identified in the extracellular medium. The possible comparisons between the typical characteristics of these cells and those of the odontoblast and pulpal fibroblasts were discussed.


[Amelogenesis imperfecta--structural, ultrastructural and radiocrystallographic study].

Teeth with amelogenesis imperfecta were obtained from three members of the same family, and studied through convergent technics of investigation: classical histology, scanning electron microscopy, high resolution electron microscopy, and crystallographic analysis. The results were compared with theoretical computer calculations. Enamel abnormalities related to the shape and irregular distribution of the crystals. Some needle-shaped crystals were found together with large ones, roughly rectangular. 42% of the crystals were distorted. Widened interplanar spacings were evidence of an hypomineralization. However, the interplanar spacings observed in high resolution electron microscopy, as well as the crystalline degree of the crystals, studied through classical crystallographic methods, revealed an apparently sound hydroxyapatite


Chemical analysis of a sulphated macromolecule isolated from rabbit submandibular gland.

Chemical analysis of a sulphated macromolecule isolated from the rabbit submandibular gland showed that about 70 per cent of the dry weight could be accounted for in terms of amino acids of which the acidic amino acids, proline and alanine were the most abundant. Total carbohydrate was 11%. Galactose was the main neutral sugar but galactosamine, glucosamine, neuraminic acid, glucose and mannose could also be demonstrated. Sulphate accounted for 1,4%. No uronic acid was found. The data indicate that the sulphated macromolecule from the rabbit gland is in fact a sulphated glycoprotein.


[Thermoffgraphy of teeth].

In order to study the behaviour of materials when inserted into the oral cavity, experimental models must be arranged and a knowledge of the intra-oral thermal distribution and the thermal exchanges is necessary. The temperature distribution at the surface of teeth was studied by two thermographic methods: the infrared method and the liquid crystals method. Some results were presented as well as the advantages and disadvantages of each of these methods.


[Histomorphologic examination of the submaxillary gland of the rabbit (Oryctolagus cuniculus)].

The histological study of the sub-mandibular gland of the adult rabbit was followed by a study of the post-natal development until the age of 15 days. The presence at birth of acinar and intercalated granular duct cells allowed a precise study of these structures and showed a high positive differential growth of the intercalated ducts from the tenth to the fifteenth day.


Human deoxythymidine kinase. I. Purification and general properties of the cytoplasmic and mitochondrial isozymes derived from blast cells of acute myelocytic leukemia.

Two forms of deoxythymidine kinase from blast cells of acute myelocytic leukemia were identified by electrophoresis. One was associated mainly with the cytoplasm and the other with mitochondria. Both isozymes were separated and purified by differential affinity column chromatography which resulted in 2416- and 1634-fold purification of the cytoplasmic and mitochondrial enzymes, respectively. Affinity gel was prepared by linkage through position 3' of deoxythymidine. Each enzyme had the same electrophoretic mobility in the purified state as it did in the enzyme derived from the corresponding subcellular fraction of the homogenate. Thymidine phosphorylase was not retarded by the affinity column. The purified cytoplasmic and mitochondrial deoxythymidine kinase had different molecular weights, sensitivities to inhibition by ammonium sulfate, activation energies for the reaction and divalent cation requirements. Adenosine, guanosine, and cytosine 3':5'-monophosphates, putrescine, spermine, and spermidine were neither activators nor inhibitors of either deoxythymidine kinase.


A virally induced osteosarcoma in rats. A model for immunological studies of human osteosarcoma.

Inoculation of Moloney sarcoma virus into the medullary canal of the tibia in newborn Wistar-Lewis rats resulted in an initially localized osteosarcoma which usually metastasized to the lung and resulted in the death of the animal within four to five weeks. Tumor cells were grown in tissue culture and used as target cells in the assay of lymphocyte-mediated cytotoxicity using a microcytotoxicity and a radioisotope labeling method. Lymphocyte-mediated cytotoxicity was demonstrated throughout the course of the clinical disease as well as in a small number of animals which showed spontaneous regression of their tumors. Serum factors which could "block" or augment the cellular response were also identified. This model resembles the spontaneous osteosarcoma of humans in many respects and may be useful for studies of the human disease.


Virus-induced osteosarcoma in rats.

An experimental model for osteosarcoma was developed in which, after Moloney murine sarcoma virus was injected into the tibial marrow space of three strains of inbred neonatal rats, a highly malignant neoplasm arose within ten days. This tumor was readily maintained in tissue culture and was transplantable to adult rats. It arose in the metaphyseal marrow of several bones, was locally invasive, metastasized to the lungs, and histologically resembled osteosarcoma.


Immunogenicity of virus-induced rat osteosarcoma.

The immunogenicity of a virus-induced rat osteosarcoma was studied utilizing the lymphocyte microcytotoxicity test. Intratibial injection of murine sarcoma virus (Moloney) resulted in the development of palpable tumors at the injection site which on histopathological examination appeared to be osteosarcomas. In 73 per cent of animals injected these tumors progressed and metastasized to the lungs. Lymphocytes from these "progressor" animals demonstrated an ability to kill osteosarcoma cells in vitro (as quantitated in the microcytotoxicity test) while serum from these animals abrogated or blocked the cell-mediated cytotoxicity. In the remaining animals the tumors either failed to develop or regressed spontaneously. Lymphocytes from these "regressor" animals also demonstrated cytolytic activity against osteosarcoma cells in vitro, but serum failed to block the lymphocyte-mediated cytolysis. Both regressor and progressor groups demonstrated humoral cytotoxic antibodies to tumor antigen on the basis of the ability of their serum to kill tumor cells in vitro.


Immunological studies in murine osteosarcoma. Immunogenicity, growth kinetics, and immunotherapy.

A transplantable murine osteosarcoma is described. Following transplantation into a syngeneic mouse the tumor grows rapidly and kills the mouse with pulmonary metastases simulating human osteosarcoma. A cell-mediated antibody response is evoked in the host mouse as demonstrated by in vivo and in vitro tests. The number of pulmonary metastases may be decreased with adjunctive immunotherapy following excision of the primary tumor. Immunotherapeutic materials include BCG and isologous cells treated with Vibrio cholerae neuraminidase.


Inhibition of streptococcal adherence by human oral secretions and its possible relationship to dental caries.

Oral secretions were collected from 100 human volunteers, concentrated, and assayed for their ability to inhibit glucan-dependent adherence of S mutans strains to glass. Some samples were found to contain adherence inhibition activity. The inhibitor was heat labile and nondialyzable but dependent on the presence of a dialyzable molecule. Comparison of activities with the caries experience (DMFT) showed that individuals with the highest activity had significantly lower mean caries scores, but that cariesfree donors did not differ significantly from caries-positive donors in mean adherence inhibition activity. These results suggest that some persons may have substances in their oral secretions that play a role in resistance to dental caries.


Effects of antibodies on adherence and cell-associated glucan production by Streptococcus mutans cells.

Studies reported here show that hyperimmune rabbit serums can have profound inhibitory effects on adherence of S mutans to smooth surfaces and that this reduction in adherence is correlated with the reduction of CAG. The latter was measured by an assay developed in our laboratory that estimates CAG production by measuring the uptake of 14C glucose-labeled sucrose into components which can be extracted by dilute alkali. This is a direct demonstration of the effect of antibody on a metabolic function of S mutans that is important in virulence. The direct correlation bewteen inhibition of CAG production, and inhibition of adherence by an antibody, suggests that the inhibition of adherence is brought about by reduction of CAG synthesis. Further studies reported here show that the inhibition of adherence and of CAG synthesis is much more effective in homologous antiserums as compared to heterologous antiserums. These results point to the need for in vivo experiments to test the effects of vaccines on colonization by heterologous as well as homologous S mutans strains.


Serum and salivary antibodies to cariogenic bacteria in man.

Antibodies in serum and parotid saliva against cell wall preparations from four serotypes of S mutans were examined in 110 subjects aged 18 to 25 years. In subjects with no detectable carious lesions, significant negative correlations were found between the DMF index and serum IgG and IgM antibodies, especially in S mutans of serotype c, whereas positive correlations were found between the DMF index and salivary IgA antibodies. In subjects with active caries, positive correlations were found between serum IgG antibodies and S mutans (serotypes c and a) and the DMF index. Sequential antibody analysis during a period of up to 32 months showed that development of carious lesions was associated with a rise in serum antibody titer to S mutans, but no change was detectable in salivary antibodies. Treatment of caries led to a decrease in serum IgG and IgM antibodies to S mutans cell wall, but in parotid saliva an increase in antibody titer to a culture extract of S mutans was found. The results support the concept of dental caries as an infective disease and suggest that serum antibodies may contribute to caries immunity in man.


Immunogenicity of cell wall and plasma membrane components of some oral lactic acid bacteria.

It is evident that characterization of any serum with respect to its specificity, and class of antibody showing that specificity, is essential for consistent serological investigations. It must also be emphasized that a particular regimen of injection of the same immunogen preparation into the same animal species will not always produce the same immunologic response.


Variations in surface polymers of Streptococcus mutans.

The cell wall composition of strains of S mutans with respect to sugars and proteins appears to be correlated to the serological grouping although groups c and E are rather similar. There also appear to be similarities in the structure of the polysaccharide formed by the glycosyltransferases from organisms of serological groups b and d. However, the activity of these enzymes appears to be variable in these groups. The most noteworthy difference found was that between the three Ingbritt strains. All three strains gave identical results with regard to their cell wall composition, and presumably this would mean that they were identical serologically. However, Ingbritt LH differed considerably from both the others in the types of polysaccharide formed by their glycosyltransferases from sucrose. Ingbritt B was a reisolate from monkeys, whereas Ingbritt LH was maintained in laboratory culture, and this may explain the difference. Clearly, more work will be required to explain this difference and as c strains are commonly isolated from plaque, it would seem desirable to clear up this point.


Some serological cross-reactions between Streptococcus mutans, S sanguis, and other dental plaque streptococci.

From the preliminary observations described in this report, the following conclusions may be drawn. When attempting to produce diagnostic antiserums specific for S mutans, S mitior, or S sanguis, care must be taken to eliminate cross-reactions as a result of antibodies against extracellular glucans or dextrans. Other antigenic components, associated with the cell wall, may be common to different species. One soluble protein or polypeptide antigen normally present in S sanguis and S mitior may also be demonstrated in certain strains of S mutans. Antiserums prepared against S sanguis, S mitior, or S mutans should be carefully checked for interspecies cross-reactions before being used for identification purposes.


Streptoccus mutans dextransucrase: purification, properties, and requirement for primer dextran.

We attempted to purify dextransucrase from S mutans strain 6715 to investigate its properties and determine if multiple species of the enzyme existed. It was concluded that the properties of this enzyme such as the pH (5.5), temperature (37 C) optimum, and Km for sucrose (3 mM) are very similar to those reported for S sanguis, S bovis, S mutans strain OMZ-176 isozymes, S mutans strain GS-5, and the single dextransucrase purified from S mutans strain HS-6. The IEF enzyme preparation consisted of two enzyme species, possibly differing in their ability to synthesize different dextran linkages. The minor enzyme activity demonstrated a strict primer dependency. Similarly, primer dependency has been reported for dextransucrases from S mutans, S sanguis, and L mesenteroides. S mutans strain 6715 dextransucrase also showed both the insertion and stepwise mechanisms for dextran synthesis. Sucrose was the sole glucose donor, whereas dextran was a specific, highly efficient glucose acceptor. The complex primer kinetics are not fully understood at this time and require further investigation. Without linkage analysis of the products of our enzymes, we can only postulate that each enzyme has a different function in the synthesis of interresidue and interchain alpha1-3 and alpha1-6 bonds. Insoluble dextran synthesis may involve a special enzyme mechanism characteristic of S mutans. This synthesis would require both enzymes, possibly in some aggregated form, with one enzyme synthesizing endogenous primer dextran. This endogeneous primer or some cell wall polysaccharide could stimulate both enzymes to rapidly synthesize heterogeneously linked insoluble dextran.


Multicomponent nature of the glucosyltransferase system of Streptococcus mutans.

The glucosyltransferases of S mutans 6715 were resolved into two major fractions. One fraction synthesized water-soluble glucans and the other made water-insoluble glucans. Each fraction was found by polyacrylamide gel electrophoresis to be composed of several catalytically active species, apparently glycoprotein in nature. Treatment of the glucosyltransferases with dextranase in the absence of sucrose caused an interconversion of enzyme forms concomitant with a time-dependent loss of enzyme activity, but did not appear to remove significant amounts of the carbohydrate associated with the enzymes. Comparison of enzyme activity patterns on polyacrylamide gels of the five different S mutans serotypes further emphasizes the complexity of the glucosyltransferase system from this group of microorganisms.


Academic tenure and collective bargaining in American dental schools.

In thier survey of organizational structures in American dental schools, Dilts and Fields reported that the organization and administration of dental schools are of importance in the operation and attainment of educational goals. If one institutional goal is to provide faculty with attractive working conditions, then academic tenure and collective bargaining are important. In this respect, dental schools run true to higher education form. Having great variability, tenure systems were reported to be universal in dental schools. On the other hand, collective bargaining was found to be a new phenomenon on trial. The experience of dental schools with academic tenure and the trial of collective bargaining are of some interest to all college educators. Dilts and Fields concluded that "Although dental education is traditional in nature, resisting changes as do other phases of higher education, the results indicate that dental education is dynamic and is responding to internal as well as external needs." Dental educators may wish to follow these tenure and union issues to help determine successful policies for the conditions of dental faculty employment.


Suggestions for teaching and evaluating a course in community dentistry.

A new approach to the teaching of behavioral sciences has been evaluated with one class of dental students. The findings suggest that educational environment and perceived qualities of instructor supportiveness are essential to the effectiveness of a socially oriented educational program.


The basic science curriculun problem in dental education: some causes and solutions.

At present there is no established purpose generally agreed on by members of the dental profession for the basic sciences in the dental curriculum. Such a purpose, supported by the entire profession, is considered a necessary first step in improving the basic science curriculum. Substantive basic science courses should be taught by instructors, holding a Ph.D. degree. These basic science instructructors, however, need the respect of the clinical faculty in order to be effective in teaching dental students. They also need to be given professional opportunity equal to that given clinical faculty if they are to commit themselves to dental education. The role of the clinical faculty in teaching the scientific basis of clinical methods is described, and the need for cooperation and communication between the basic science and clinical faculties is emphasized. Regularly scheduled faculty workshops are recommended for this purpose. A decrease in student contact time for clinical faculty is also suggested. The dental profession, led by dental educators, with advice from other health professionals, dental students, and the general public, is the logical body to define the purpose of basic science in dental education.


Motives to enter the dental profession: students, practitioners, faculty.

1. The dental student, the private practitioner, and the dental educator have similar self-motives related to an educational process which includes learning to develop to full potential and having the freedom to carry out one's ideas. 2. The motives perceived by dental students as important for the private practitioner are not the same as those the private practitioner perceives for himself. The student perceives good salary and a community reputation, while the practitioner perceives a continual educational process with freedom to carry out his ideas as the primary motive for entering the profession. The student and the practitioner are aligned on most of their self-motives. 3. The motives of the dental educator parallel those of the practitioner more than they parallel those of the student.


Experiential education for dental students at the University of Kentucky.

An experiential educational system at the University of Kentucky College of Dentistry has been described. It consists of a summer externship program and an individualized externship program offered during the academic year. These programs provide dental students with extramural educational experiences in private dental offices to prepare them better for the practice of dentistry and to expose them to forces affecting the delivery of dental services.


A fourth-year orthodontic elective in an educational group practice.

An educational group practice is described in which a fourth-year dental student actively observes and participates in orthodontic decision making and treatment delivery. The student takes part in patient treatment under the direct supervision of a second-year orthodontic resident. The residents reinforce the skills which the students learn in class and laboratory. In this way an effective learning experience results for both the resident and the fourth-year student. Students also attend patient care conferences, where treatment points of view and sequences are discussed. In this way, students have a first-hand glimpse of what a career in orthodontics might be like.


A dental school hypertension screening program.

This paper has described a hypertension screening program at the Medical College of Virginia School of Dentistry. The program, which has been in operation for over two years, incorporates referral to a physician and a system of repeated follow-ups. The results indicate that the program has been successful in that 134 of a total of 141 patients with suspected hypertension have been successfully referred.


Pass/fail versus A-F grading: a comparative study.

This study compared achievement when one half of a class was assigned to take a course on a pass/fail basis and the other half received a letter grade. The unique characteristics were as follows: (1) students were assigned to A-F and pass/fail groups rather than allowed to choose the grading system, (2) virtually no other course competed for study time, and (3) the course constituted a major field of study for the student. The results showed no significant difference between the two groups in achievement on three separate examinations.


Reason and remedy for conflicting reports on comparative effects of steel scalpel and electrosurgical cutting on gingival tissues and alveolar bone.

The fact that electrosurgical cutting is governed by factors that have no influence on steel scalpel cutting is responsible for discrepancies among the results of investigations of the modalities. The investigator's equal expertise in the use of both modalities is a prerequisite for accurate comparative investigations of the effects of electrosurgical and steel scalpel cutting. Eleven specific factors that govern the efficacy and quality of electrosurgical cutting and that can, therefore, ensure consistently reliable histologic results and accurate conclusions have been mentioned.


How to deliver a comprehensive preventive dentistry service that dental insurance carriers can underwrite.

The successful practice management of preventive dentistry requires that it be comprehensive and include both chairside and counseling procedures. The chairside clinical procedures are a prophylaxis, topical application of fluorides, application of pit and fissure sealants, and fabrication of mouth-guards and space maintainers. The counseling procedures include plaque control and nutritional guidance. The caries activity test can be used as a means of monitoring excessive sugar intake. It is the responsibility of the dentist to determine the preventive dentistry needs of his patient based on the latter's caries score, periodontal, gingival, and plaque indexes, and diet evaluation. Since patients are prone to certain dental problems during particular age periods, the preventive management procedures must consider the existing and anticipated dental problems on the basis of the patient's age. Each of the preventive services is objective in nature because it involves either chairside or counseling procedures. During the counseling service,worksheets and clinical case notes are kept as part of the patient's dental record. The progressive effectiveness of the home-care preventive dentistry counsling procedures can be measured by scores and indexes. The frequency of repeating the service depends on proven clinical merit and the individual needs of the patient. The delivery of preventive dentistry services can be monitored  by dental insurance carriers through peer review of clinical services, data sheets, case notes, a preventive dentistry record, and by patient questionnaire. A method for managing, measuring, and monitoring an objective, comprehensive preventive dentistry service has been presented so that the insurance carrier can underwrite this type of coverage as part of its dental insurance plan.


The undiagnosed split-root syndrome.

The split-root syndrome is an often misdiagnosed painful condition. The major causes of the splits have been discussed. In addition, classical symptoms associated with this syndrome have been illustrated by two case reports to facilitate the syndrome's recognition.


Dental health: what is being taught to college students.

An analysis of the dental health material in all college-level, health education textbooks published between 1966 and 1973 showed a deficiency in the amount, the thoroughness, and the quality of the dental health information given. Realibility of information from one source to another is low, and some information is inaccurate. On the basis of information in these textbooks, serious questions are raised concerning the adequacy of dental health education in college-level health education courses. The dentist is advised to review and to examine the dental health information that is being taught in these courses.


Teenagers' attitudes, knowledge, and behaviors related to oral health.

This survey documents the meagerness of teenagers' knowledge and behavior about dental health. They knew that brushing before bed and checkups are desirable. Otherwise, they were sorely lacking in fundamental knowledge about what is needed for optimum oral health. Except for 6 of the 2,517 sophomores, there was no evidence that they knew about plaque. Small minorities thought about using floss and then for removal of food, not plaque. Fewer than a fourth knew that periodontal disease was a disease of the gingiva. Brushing was the major oral health practice. But it was rarely checked with disclosing tablets and mouth mirrors. It is questionable whether most knew about these. Flossing was rarely done. Curtailment of sweet foods or drinks as an oral health measure was even rarer. One would expect some improvement in the six years since this study was done, given the greater emphasis on plaque control in dentistry. Yet, the possibility that many more of a similar group of teenagers at this time would be preventively oriented seems unlikely. Plaque control programs are not that common in dentistry. And only 42% of the sample studied could be said to go to the dentist for preventive checkups in the first place. Morever, recent interviews I have done with patients at a public clinic did not uncover much awareness or behaviors related to plaque control. The respondents in the study reported here were students in their tenth year of public school. Their schooling was preparing them for many things, including common problems of everyday life. Very few problems are as common as tooth decay and periodontal disease. Yet the teenagers knew little about and were doing relatively little to prevent these problems. Obviously, their need for instruction is great.


A survey of accredited dental technology education programs in the United States.

A study was made of current educational methods and prosthetic technology used in the accredited dental technology education programs in the United States. Some of the results have been compared with the findings of a similar study in Britain and several differences have been noted. The results of this study and of the British one refer to accredited educational programs and do not necessarily reflect the procedures used in dental practice or in commercial dental laboratories.


Dentists and sub-bachelor's degree allied health manpower.

The responses of 176 randomly selected dentists to a written questionnaire were used to assess the attitudes and perceptions of dentists toward subbachelor degree allied health workers. Particularly, demographic characteristics of dentists who employ allied health workers, the patterns of how the dentists utilize the allied health workers, and the dentists' attitudes toward aspects of allied health training were the main points covered. Findings indicate that practicing dentists have a mixed view of the role that paramedical workers can have in increasing dentists' productivity. Although most surveyed dentists agress that auxiliary personal are useful in filing nondental roles, many dentists also are delegating dental functions to these workers.


A major gene controlling warfarin-resistance in the house mouse.

The spread of a "cream" mutant in a wild population of house mice is reported. The hypothesis that the gene responsible for the colour, extreme chinchilla, ce, has spread because of linkage with a major gene for warfarin-resistance, is tested by a linkage backcross. The results prove that a major gene does exist, that it is very closely linked with frizzy, fr, in chromosome 7, which in turn is linked with ce, that it is fully dominant in females at 4 months of age, and that its partial dominance in males is under the control of modifiers. The symbol War is proposed for the gene. Its position in chromosome 7 is analagous with the position of the resistant gene, Rw2, in the rat in the analagous chromosome. The adaptive significance of the finding is discussed, as also are reports of certain other mutants in wild populations of mice.


A bacteriological survey of washrooms and toilets.

A survey of the bacterial flora present at various positions in 130 male and female washrooms and toilets is reported. Several bacteria of faecal origin were found in large numbers: the areas likely to be the most important sources of cross-infection from faecal contamination are indicated. The results are used to assess priorities for disinfection.


Antibiotics and the Aberdeen typhoid outbreak in 1964.

This paper gives an abbreviated account of part of a research programme which followed the Aberdeen typhoid outbreak in 1964. Chloramphenicol, the main antibiotic used in treatment, was shown to have a minimum inhibitory concentration (MIC) of between 5 and 2-5 mug./ml. for the S. typhi phage type 34 of the outbreak. The MIC for methacycline was between 5 and 2-5 and 2 mug./ml. Whereas the deep and shallow broth techniques used gave similar results with these antibiotics, the MIC for ampicillin, and also cephaloridine, was less in the deep than in the shallow broths. Serum assays in patients given ampicillin or cephaloridine yielded abnormally high concentrations of both antiboitics when S. typhi phage type 34 was the test organism whereas, with other test organisms, the concentrations were within expectation. These abnormally high values fell within expected values when the sera under investigation had first been heated to 56 degrees C. for 30 min. before assay against the S. typhi of the outbreak. The findings with ampicillin suggested that dosages given were satisfactory. With cephaloridine the concentrations found in patients' sera seemed to show that twice daily doses of 0-5 g. fell short of adequacy.


A preliminary study of the effect of contact with environmental mycobacteria on the pattern of sensitivity to a range of new tuberculins amongst Ugandan adults.

A range of new Tuberculins prepared from extracts of living organisms belonging to 12 mycobacterial species has been used to assess the effect of BCG immunization and contact with environmental mycobacteria on Ugandan adults. A total of 2,456 tests were carried out on 562 people, 86% of whom came from three areas selected for special study. These areas were chosen on the basis of occurrence of leprosy and M. ulcerans infection and on data concerning the distribution of environmental mycobacteria. It was found that the effect of BCG was small compared with that previously observed amongst Kenyan schoolchildren, but that the effect of geographical origin was considerable. There was some correlation between the percentages of reactivity to the reagents and the frequency of mycobacteria in the environment.


Age-sex distribution of various diseases with particular reference to toxoplasmic lymphadenopathy.

An account is given of some human diseases which affect one sex more than the other. An age-sex realtionship has been noted among British patients with acquired toxoplasmic lymphadenopathy. This is compared with the findings of other European workers. A possible explanation is offered taking all these diseases into consideration together with some of the experimental work done in animals and some of the variations in immunological responses by man.


A quantitative comparison of the sensitivity of serological test for bovine brucellosis to different antibody classes.

Brucella-specific antibodies of different immunoglobulin classes were quantitatively evaluated with respect to their efficiency in serological tests for bovine brucellosis. IgM reacted more efficiently than IgG1 and IgG2 in both the Rose Bengal plate test and serum agglutination test. The complement fixation test was found to be slightly more sensitive to IgM than to IgG1 and did not react to IgG2. IgM was, however, partly inactivated when heated at 60 degrees C. in the presence of serum.


The hamster as a secondary reservoir host of lymphocytic choriomeningitis virus.

Exposure of weaned hamsters to an environment contaminated with LCM virus shed by tolerantly infected mice led to short subclinical infections. If infection occurred in early pregnancy, the young appeared normal at birth but their tissues were highly infective. For two to three months their bites and urine were also highly infective. A viraemia did not persist long enough for successive vertical transmissions of the infection to be likely. However, the viruria persisted in most prenatally infected hamsters for at least eight months and under simulated field conditions was a potent virus source for contact infections, leading to further generations of prenatally infected young. In the absence of the natural reservoir host, such long-term carriers could have been a major factor in causing the build-up of infection in colonies of hamsters which, when purchased as household pets, led to a recent spate of human clinical infections in Germany and the U.S.A.


Epidemic of echovirus 19 in the north-east of England.

We report the first large-scale outbreak of echovirus 19 infection. It occurred in the north-east of England during the summer and autumn of 1974. The virus was isolated from 268 patients in the region. The infection spread from the urban to more rural areas, reaching a peak in mid-August. Males were affected more often than females in the ratio 1-6:1. Half of the patients were under eight years of age, relatively few were over 35 years. Aseptic meningitis and upper respiratory infections were the commonest presentations, though a wide range of other diseases occurred including gastroenteritis, myalgia, pericarditis, undifferentiated pyrexia, rashes and a syndrome analagous to bacteraemic shock. There was no evidence that the pattern or severity of the disease changed during the outbreak. Infants under the age of six months were more seriously affected than older children and adults. All patients except one made an uneventful recovery. Of the routine tissue culture cells HEp2 and HeLa were by far the most satisfactory for virus isolation.


[Temperature dependence of inner structure in dental amalgam (author's transl)].

The problem of temperature dependence of inner structure in dental amalgan has been studied by several investigators. But so far as the present authors are aware, researches of the inner structure in amalgam at successive temperatures have not been published. In the present paper, the temperature dependence of structure are observed under a hot stage microscope with monitor television and recorded by vidio tape. The specimen is placed in furnace of microscope, and rised temperature by W heater. The contrast of structure increase very much at about 50 degrees C, and even uetched specimens reveal the structure clearly. The structure change remarkably above 60 degrees C and 80 degrees C. It seems that the main reason are the decomposition of gamma 2 phase and amalgamation of residual mercuries in the specimen. The structure of specimen polished and etched after cooling from 100 degrees C are similar to that before heating very much without fine structure in the unreacted particles. It has been deduced that the resemblance of structure concern the reversibility of mechanical properties proposed by Jørgensen, Otani and Kanai.


[Mechanical properties of Co-Cr-Ni ternary alloys (author's transl)].

Mechanical properties of Co-Cr-Ni ternary alloys (0approximately90%Co, 10approximately40% Cr, 0approximately60% Ni by weight) were investigated. It was found that some alloys containing chromium from 30% to 40% had high strength, hardness and elongation but alloys containing nickel from 0% to 20% had low elongation and 60% Co-40% Cr binary alloy was higher than 70% Co-30% Cr binary alloy in tensile strength, hardness and elongation.


[Changes of ciscoelastic behaviour during curing of polyether rubber impression material].

To obtain a precise  impression, it is indispensable to understand changes of physical property of the material used, during curing. The authors measured the viscosity and the storage modulus of polyether rubber which was recently introduced as a commercial impression material and tried to make clear the curing mechanism of the material. The less the amount of catalyst added to the base material, the more approximative is the behaviour to the first-order reaction. But according as the amount of catalyst increases the behaviour becomes not to be regarded as the first-order reaction, i.e., it is surmised that the curing reaction becomes so complicated. The more the amount of catalyst and the higher the temperature after mixing, the shorter is the setting time. The curing reaction of polyether rubber impression material is supposed to be completed in about 3 hours after mixing. Polyether rubber impression material showed the highest storage modulus among the three rubber impression materials not used, namely, polyether, polysulfide and silicone rubber. The values of this highest modulus of polyether rubber were about 2.4approximately2.8 times of those of polysulfide and silicone rubber impression material in 3 hours after mixing.


The concept of oral rehabilitation.

Dentistry must re-examine its professional obligations towards the patient and consider whether its present basis is too rigidly technical. Oral rehabilitation can be defined in terms of the restoration of function and aesthetics. However, it must include also a philosophy of concern for an oral invalid who may require continued and varied in the management of his disability. The understanding of this concept requires an analysis of the meaning and impact of an oral disorder on an individual, and the responsibilities of those who have to provide him with guidance. Consideration must be given to the reflection of these principles of care on the teaching of dental students.


A long-term prognosis for the fixed saddle-bridge. A study of 100 constructions.

This report constitutes a long-term study of 100 saddle-bridges applied by the author during the years 1958-1973. The aim of the investigation has been to assess the prognosis for this form of therapy. The probability that a saddle-bridge will still be functioning completely, without repair, after 5 years is 93%, and after 10 years (as also after 12 years) 83%. Only 12% of the appliances had been removed 12 years after the application. The risk of defects is about the same during the first 5-year period after the application as it is during the second and the third 5-year periods. A comparison between saddle-bridges applied before and after 1965 shows no demonstrable difference as regards the 5-year prognosis in spite of modifications with respect to range of indication and therapy. The causes of the defects have been divided into biological and technical. During the first 5-year period technical defects appear to be in the majority, whereas during the later stages, biological defects predominate. Background factors such as sex, the age of the patient, length of saddle, localization in the jaw do not prove to have any appreciable importance for the prognosis. There is, on the other hand, a significantly better prognosis when the opposing jaw is furnished with the patient's own teeth and/or fixed bridges than with a removable denture. The author points out that from the result of the study, the saddle-bridge has such a good long-term prognosis that its range of application for fixed constructions should be considerably extended.


Reflex activity in the masseter muscle of young individuals. I. Experimental procedure - results.

The monosynaptic myotatic (jaw jerk) potential (MSP) evoked in the relaxed masseter by a tap on the chin and recorded electromyographically in this muscle (latency 6-3 ms, duration 5-9 ms) was similar in subjects with, or without TMJ clicking. The latency of the myotatic potential was significantly shorter (5.8 ms) when evoked during isometric contraction. The duration was 5-2 ms. A potential with similar characteristics as the MSP was evoked by TMJ clicking, as we believe by excitation of muscle spindles from tissue transmitted vibrations (latency 5-5 ms, duration 5-6 ms). The TMJ click evoked MSP could in the contracting massester be followed by silent periods (SPs) both of the early (latency about 10 ms) and the late type (latency about 50 ms). A tap on the chin during isometric contraction of the jaw elevators, was followed by an SP of the early type (latency 12-2 ms, duration 17-5 ms) and sometimes by an SP of the late type (latency 58 ms, duration 18 ms). The late SP occurred significantly more often in patients with TMJ-dysfunction. The period of lower activity following an MSP can be divided into two phases: a first phase with a complete electrical silence, denoted SP, and a second phase during which the activity is slowly increasing to reach the control level. This latter phase will be called "depressed activity" (DA) and is introduced as a new parameter. The SP with tooth tapping (latency 10-5 ms, duration 9-4 ms) was similar in groups with or without TMJ clicking. The superimposed MSP (SMSP) preceding the SP at tooth tapping is supposed to be a manifestation of the "load-compensation reflex".


Utilization of elecrical conductivity as an alternative method of assessing marginal leakage of pit and fissure sealants.

The electrical conductivity readings of extracted human teeth uere taken: prior to placement of pit and fissure sealants; immediately after placement of the pit and fissure sealants; 2 weeks after immersion of the specimens in distilled water at 37 degrees C; and after 7200 strokes on a toothbrushing machine. The specimens were then immersed in dye for 24 h, sectioned and evaluated for evidence of dye penetration. The electrical conductivity readings were then compared to dye penetration results to determine if a correlation existed. A positive correlation existed between the electrical conductivity readings and dye penetration. Threshold values of electrical conductivity existed (which varied for each sealant) - readings above these threshold values indicated sealant failure or leakage. The possibility of using electrical conductivity as a diagnostic tool is definitely worthy of further research - particularly its potential as an in vivo method of assessing leakage.


Frequency and location of artificial crowns and fixed partial dentures constructed at a dental school.

The material consists of patients who received single crowns and fixed partial dentures at the Department of Prosthetics, Dental Faculty, University of Oslo in the period 1967-73. Two-thirds of the patients were women, and about two-thirds of the restorations were made in the maxilla. A total of 3275 crowns were received by 2145 patients. On average, maxillary teeth were crowned 7 years earlier than mandibular teeth. A total of 1393 fixed partial dentures, consisting of 6835 units, were made for 1368 patients.


Frequency of symptoms of mandibular dysfunction in young Swedish men.

The occurrence of symptoms of dysfunction of the masticatory system was studied in 253 Swedish men from the region of Stockholm with an average age of 19 years. Besides inquiry by questionnaire regarding subjective symptoms a clinical functional examination of the masticatory apparatus was performed. Fourteen per cent were aware of clicking of the temporomandibular joint and 12% of other symptoms of dysfunction such as difficulties in opening the mouth wide, locking and pain on performance of various movements of the mandible. In the clinical investigation, symptoms of dysfunction were noted in 28% of those examined, mainly in the form of tenderness to palpation over the temporomandibular joints and of the masticatory musculature as well as difficult, painful and irregular movements of the mandible. Individuals with clinical symptoms of dysfunction of the masticatory system had a higher frequency of other joint and muscle symptoms, clicking of the temporomandibular joint and occlusal disturbances in the form of balancing side interferences, than those without clinical symptoms. Balancing sides interferences were the only occlusal disturbance that was significantly correlated with the symptoms of dysfunction (pain on movement and tenderness to palpation).


Costs of publicly financed dental care for children in three different types of practice settings.

This analysis of the Chattanooga Program has provided preliminary findings on the relative cost of providing dental care through three different modes of care delivery: private practice, public fixed clinics, and public modile clinics. Significant differences in costs were found. It is reasonable to conclude, tentatively, that public services were being used more efficiently than private services in the delivery of dental care involved in this program. The results contest the findings of previous studies which indicated that mobile clinics were relatively inefficient. This study, however, based on a limited time period and refers to a specific program. It would, therefore, be inappropriate to generalize too hastily from the results. At this time, further research is being conducted to extend the period of analysis, and to deal explicitly with differences in patient characteristics, service mixes, and quality, to explain the economic reasons for the apparent differences in efficiency by delivery mode, and to consider the implications of the findings for dental policy.


The effect of toothbrushing frequency on oral hygiene and gingival health in school children: reassessment after two and one-half years.

An epidemiological survey of brushing frequency, oral hygiene (OHI-S), and gingival condition (GI modified) was conducted on 290, 12- to 15-year-old schoolschildren. The purpose of the survey was to compare the clinical findings with the children's states frequency of toothbrushing. Since the same children had participated in a similar study approximately 2 1/2 years earlier, it was also of interest to determine what effect, if any, a change in reported brushing habits might exert over the oral status of the children. As in a previous study, the stated level of brushing activity was high. Approximately 46 percent of the children claimed to brush twice a day, and 40 percent once a day. The poorest oral hygiene and highest level of gingivitis were associated with the group of children that claimed to brush less than once a day. In general, the children that claimed to brush their teeth more frequently had lower mean OHI-S and GI scores indicating less oral debris and gingivitis. For males-females combined the optimal effect on oral hygiene and gingival condition, on a statistical basis, was detected at the level of twice-daily brushing. Increased brushing frequency beyond this level did not produce significant improvement in OHI-S or GI scores.


Synthesis and biological activities of some N4-substituted 4-aminopyrazolo(3,4-d)pyrimidines.

Syntheses and biological activities of 26 N4-substituted 4-aminopyrazolo[3,4-d]pyrimidines as analogs of naturally occurring modified nucleic acid bases, N-(purin-6-ylcarbamoyl)-L-threonine and N6-(delta2-isopentenyl)adenine, are described. 4-Aminopyrazolo[3,4-d]pyrimidine was converted into the desired intermediate, ethyl pyrazolo[3,4-d]pyrimidine-4-carbamate (2). 4-Ureidopyrazolo[3,4-d]pyrimidines (6-26) were prepared by displacement of the ethoxy group of the carbamate 2 by amino acids and a variety of amines and by a reaction of 4-aminopyrazolo[3,4-d]pyrimidine (1) with isocyanates. N4-Alkylaminopyrazolo[3,4-d]pyrimidines were generally prepared by displacement of the chlorine from 4-chloropyrazolo[3,4-d]pyrimidine with various amines. Several analogs exhibited moderate to very good growth inhibitory activities against cultured L1210 leukemia and 6410 human leukemic myeloblasts.


Intermittent pressure in the management of post-traumatic oedema and lymphoedema. The rationale and description of a new method.

This paper describes the use of intermittent pressure to reduce oedema of the limbs by assisting resorption. The rationale of the method is outlined with emphasis on the management of traumatic oedema. A safe, simple and inexpensive device to effect the intermittent pressure is described. The results of clinical trials on 63 patients with oedema are documented to substantiate the value of the treatment.


[Cytologic diagnosis of myeloblastic leukemia via hemopericardial puncture (author's transl)].

In a case of primary aleukemic acute myeloblastic leukemia early evidence of the disease was provided by cytodiagnosis. Puncutre of the hemopericardium, the presenting symptom, showed malignant cells. Differential cytology, along with the age and sex of the patient led to a tentative diagnosis of leukemia, which was ultimately confirmed by bone-marrow studies.


Acceleration of healing of maxillary and mandibular osteotomies by use of hyperbaric oxygen. A preliminary report.

Thirty-eight osteotomy patients were treated with hyperbaric oxygen in order to determine clinically its effect on the length of osseous healing. Data accumulated from this clinical investigation indicate that hyperbaric oxygen augments clinical bone healing subsequent to osteotomy procedures.


Bacterial study of pyogenic infections of dental origin.

Fluctuant abscesses of dental origin were sampled by syringe aspiration. These samples were cultured by means of techniques suitable for isolation and growth of obligate anaerobes. Oral abscesses are usually mixed infections that include a number of different species. More than 65 per cent of the species isolated were obligate anaerobes, which indicates the need for anaerobic methods in studying these infections. Anaerobic gram-negative rods and facultative streptococci were the groups isolated most frequently.


Management of a mucoepidermoid carcinoma of the palate. Report of a case.

A case of mucoepidermoid carcinoma of the palate is presented, with emphasis on surgical treatment and postoperative care. It is thought that many oronasal communications may be prevented by the use of palatal splints relined with appropriate soft-tissue conditioners at frequent intervals.


Recurrent oral and oculogenital ulcerations (Behçet's syndrome).

The literature on Behçet's syndrome is reviewed and four cases are presented. Two of the patients were men and two were women. The age at presentation varied from 21 to 55 years. All patients had the first manifestations of the disease before the age of 25 and two before the age of 10. None presented with the complete triad of symptoms. All four had oral ulceration and either ocular lesions (two cases) or lesions on the genitals (two cases). According to the present theories, the diagnosis of Behçet's syndrome is established by the presence of any two of the triad of symptoms. We suggest that in order to be classified as having Behçet's syndrome, a patient should have oral lesions and either genital and/or ocular ulcerations.


Globodontia in the otodental syndrome.

A family of Polish extraction was studied in which massive, globe-shaped posterior teeth were found in a father and two of his sons, similar to those described in a previous family in which persons with this type of teeth also had a high-frequency sensorineural deafness. The audiograms in this family showed high-frequency air-conduction thresholds in the father and one son with globodontia and in other relatives without the tooth defect. The other son with abnormal teeth had a normal-appearing audiogram. Absence of premolar teeth and yellow-white spots of local hypomaturation of enamel on canine teeth were also findings in this kindred, as reported or observed in other kindreds. The disorder illustrates the problem of variable expressivity of a trait which makes it difficult to predict the risk of having an affected child when only one feature of a syndrome is present in a relative of a fully affected patient.


A clinical study for the control of facial mucocutaneous herpes virus infections. I. Characterization of natural history in a professional school population.

One thousand thirty-one dental and dental hygiene students, faculty and staff at The University of Michigan School of Dentistry were interviewed in order to identify those with a past history of perioral mucocutaneous herpetic infection. Subsequently, the population was followed for 9 (+/- 3) months in order to determine various parameters of disease expression. Analysis of the results indicate the following: 1. In this professional population, 20.5 per cent described prior experience with perioral herpes. No sex difference was noted. 2. Prevalence increased with age. In the faculty-staff group (mean age 32.9 years +/ 11.8) prevalence was 30.7 per cent, whereas in the student -roup (mean age, io.6 years+/- 3.8) prevalence was 17.7 per cent. Occupational and/or socioeconomic factors did not appear to account for the age-related difference in prevalence. 3. Only 40 per cent of those who related prior disease experience developed lesions within the observation period of 9 (+/-3) months. 4. The recurrence rate, based upon an observation period of 9 (+/-3) months, in those persons who related prior disease experience was found to be 1.3 episodes per year (0.1 per month). 5. Duration of lesions ranged between 3 and 17 days, with a mean of 9 days. 6. The lower lip was the most common site of a lesion. 7. Triggering factors associated with development of a lesion in order of decreasing frequency were found to be; emotional stress, exposure to sun, and illness.


Ameloblastoma containing mucus glands.

A 53-year-old woman had a large, deforming mass involving the mandible and was treated by subtotal mandibulectomy. Histologically, the mass proved to be an acanthomatous ameloblastoma that contained mucus glands. Eleven years after the mandibulectomy, the tumor has not recurred or metastasized.


Dentin dysplasia type I. Clinical, morphologic, and genetic studies of a case.

This report documents a case of dentin dysplasia Type I in a 17-year-old boy and two members of his family. The clinical, radiographic, histologic, and ultrastructural findings indicate that this condition is distinct from other heritable defects of dentin. The entity is transmitted as an autosomal dominant trait and is characterized by teeth which have a normal color and exhibit pulpal obliteration, short roots, periapical radiolucencies, and spontaneous exfoliation. Our ultrastructural findings in agreement with those reported by Sauk and associates.


Benign cementoblastoma.

An unusual case of cementoblastoma is presented. It is the second case to be published demonstrating involvement of the pulp, and it is the first instance of a cementoblastoma that appears to have evolved from an impacted tooth. A review of the literature substantiates the fact that this lesion may not be so uncommon as was previously thought, and that pain and facial asymmetry may be significant clinical features.


Fluorescence of biogenic monoamines in the human dental pulp.

Biogenic monoamines in the adrenergic nerve terminals of the human dental pulp are demonstrated by the fluorescence method of Falck and Owman. Unmyelinated nerve fibers from nerves along alveolar blood vessels may enter the pulp, although pulp nerves are composed largely of myelinated fibers. The existence of a few sympathetic fibers is demonstrated by the fluorescence method, and possible drug effects are considered.


Chelating agents: their effect on the permeability of root canal dentin.

An in vitro assessment was made of the ability of three chelating agents used in endodontics to alter the dye penetration of dentinal tubules from the root canal surface. The experiment and control for this study were within the same root. It was found that all three agents significantly reduced the dye penetration into dentin, but there was no difference among the agents in the degree of reduction of dye penetration.


[Association of chronic myelosis and cancer].

During the period between 1948-1963 a total of 3,200 tumor patients were treated in the First and Second Medical Clinics of Tg.-Mures. In these tumor patients as well as the skin cancer patients who were treated with radiotherapy the authors found in 1.5% of the patients a leukocytosis of more than 20,000. In the last ten years (1964-1974), however, in the Second Medical Clinic only, 5% of 516 tumor patients showed a leukocytosis exceeding 20,000. In the first group of patients (3,200 cases) 0.03% showed more than 50,000 leukocytes, in the other group of 516 patients 0.2% showed more than 50,000 leukocytes. These values point towards a leukemoid reaction. A shift to the left to the myelocytes or beyond in the blood picture was found in the Second Medical Clinic in 10% of patients with carcinoma during the year of 1974. In 6% of the cases erythroblasts in the peripheral blood were seen, too. This deviation occurred often independent of the total number of leukocytes and was of a temporary nature. During the same time (1949-1974) 128 patients with chronic myeloid leukemia were treated in both departments as in-patients. 6 cases (i.e., 4.6%) had a chronic myelosis simultaneous with carcinoma, in one case together with an osteosarcoma. The diagnosis was confirmed in all cases by autopsy.


The frequency, technical standard and results of endodontic therapy.

The present summary and the following papers (I--VI) have been accepted in partial fulfilment of the requirements of the degree of Doctor Odontologiae at the Dental Faculty, University of Bergen. Paper I: Tooth mortality and endodontic status of a selected population group - before and after treatment in a teaching clinic. Paper II: The apical level of root fillings made by general practitioners, undergraduate students and an endodontist. Paper III: Radiographic evaluation of endodontic treatment-a methodological study. Paper IV: The quality of the seal of root fillings made by general practitioners, undergraduate students and an endodontist. Paper VI: A radiographic follow-up of endodontically retreated roots. In this summary these papers will be referred to by the above Roman numerals. Other investigations will be referred to in the conventional manner.


[Sialolithiasis in minor salivary glands. Case report].

Lithiasis of the minor salivary glands appearently occurs more frequently than hitherto presumed and should be considered as a possibility in the clinical differential diagnosis of tumors of the oral mucous membrane. The present paper refers two cases of sialolithiasis of the labial minor salivary glands. Further, a general outline of the condition is presented based on later years' increasing number of case reports.


Biological activity of catecholamines covalently linked to synthetic polymers: proof of immobilized drug theory.

l-Isoproterenol was covalently coupled via an azo linkage to soluble copolypeptides of molecular weight 1500 and 10,000 containing an aromatic amine. The polymeric azo-isoproterenol derivatives were purified by gel chromatography which reduced contamination by the parent isoproterenol to undetectable levels (i.e., less than 0.01%) and by 6-aminoisoproterenol to less than 0.4%. Both polymeric isoproterenol derivatives were found to elicit positive chronotropic responses in isolated perfused guinea pig hearts. The mean effective doses (ED50S) for the 1500 and 10,000 molecular weight derivatives were within 1.3 and 2.0 orders of magnitude, respectively, of the ED50 of l-isoproterenol. The responses cannot be attributed to free isoproterenol because this drug could not be detected in our preparations. Neither can the observed biological activity be attributed to 6-aminoisoproterenol, since this compound's dose-response is shifted 3 orders of magnitude to the right of l-isoproterenol and 1-2 orders of magnitude to the right of the polymeric derivatives. Inotropic response decay times in isolated cat papillary muscles following washouts indicate that the polymer-bound drug does not diffuse into the muscle tissues. We feel that our findings demonstrate that under controlled conditions the catecholamines can retain biological activity while covalently bound to a polymeric support.


Distribution of 5-bromodeoxyuridine and thymidine in the DNA of developing chick cartilage.

In order to study the mechanism of the irreversible effects of BrdUrd on the differentiation of limb bud mesenchyme to cartilage, the reannealing behavior of DNA obtained from such cells was examined. Cells incubated with [3H]thymidine ([3H]dThd) during days 1 and 2 of culture incorporated label into repetitive, moderately repetitive, and unique classes of DNA. In contrast, when 5-bromo-2'-[3H]deoxyuridine ([3H]Brd Urd) was added during the first 48 hr (in the presence of 32 muM BrdUrd), the label was preferentially incorporated into a late moderately repetitive region. Simultaneous incubation of unlabeled BrdUrd and [3H]dThd revealed a selective inhibition of [3H]dThd incorporation into moderately repetitive regions. Cultures incubated during days 3 and 4 with [3H]dThd incorporated label into all three classes of DNA; however, when [3H]dThd was present during days 3 and 4 in cultures previously incubated with BrdUrd during days 1 and 2, the [3H]dThd was incorporated preferentially in the late moderately repetitive region. The melting behavior of this reannealed DNA was identical with that of the reannealed 1-2 day [3H]BrdUrd-labeled, late moderately repetitive DNA. Turnover experiments revealed that whereas there was no loss of [3H]deoxycytidine or [3H]dThd, 37% of [3H]BrdUrd activity was lost from the DNA in 2 days after removal of the isotopes.


Intracellular forms of adenovirus DNA: integrated form of adenovirus DNA appears early in productive infection.

In KB cells productively infected with adenovirus type 2, alkali-stable greater than 100S and 40-100S viral DNAs are synthesized starting 2-4 hr postinfection, i.e., before unit length (34 S) viral DNA is made. The amount of greater than 100S and 40-100S viral DNA increases when 34S viral DNA synthesis  begins, and at 16-18 hr postinfection, the 40-100S viral DNA represents 5-20% of the total intracellular viral DNA. The 40-100S viral DNA is synthesized throughout infection. Part of the 40-100S DNA synthesized 5-8 hr postinfection has a density in alkaline CsCl gradients intermediate between those of viral and cellular DNAs. This finding indicates that newly synthesized viral DNA is covalently linked to cellular DNA. Viral sequences can be excised from the cellular DNA of infected cells with the EcoRI restriction endonuclease. Fragments of viral DNA are detected in polyacrylamide-agarose gels by DNA-DNA hybridization, and these fragments correspond in size to most of the known EcoRI fragments of adenovirus 2 DNA. Viral DNA sequences in size-classes between the EcoRI-A and -C fragments are also found and probably represent viral DNA linked to cellular sequences.


Observations on polycythemia vera turning into acute or chronic granulocytic leukemia during treatment with radioactive phosphorus 32P.

In a group of 172 cases of polycythemia vera treated with radioactive phosphorus acute granulocytic leukemia developed in 3 and chronic granulocytic leukemia in 6 cases. The author believes that development of acute granulocytic leukemia during this treatment may be considered with some probability as a result of the leukemia-inducing action of ionizing radiation. Transition of polycythemia vera into chronic granulocytic leukemia seems to be a natural outcome of this complex myeloproliferative syndrome in patients with survival prolonged by treatment with 32P.


New protein in human blood plasma, rich in proline, with lipid-binding properties.

A protein that binds to a lecithin-stabilized triglyceride emulsion has been separated from plasma after removal of major lipoprotein classes by ultracentrifugation at density 1.21 g/ml. This protein, rich in proline, has been purified to electrophoretic and immunochemical homogeneity by subsequent gel and ion-exchange chromatography. In native plasma and after purification, it exists as a large particle exceeding 10(6) daltons, but a single component with a molecular weight of about 74,000 is found upon polyacrylamide gel electrophoresis in sodium dodecyl sulfate. Although the purified protein contains very little bound lipid and is not present in the major lipoprotein classes from post-absorptive individuals, it is present in chylomicrons. Its concentration in plasma varies from 12 to 41 mg/dl and is significantly correlated with that of cholesterol in lipoproteins of very low and low density but not in those of high denisty.


A thermodynamic model of regulation: modulation of redox equilibria in camphor monoxygenase.

Regulation of biological phenomena occurs in all types of systems, being manifested in many different reaction types, from allosteric behavior in proteins, through modulation in energy and information transfer, to the control of growth and differentiation in cells, organelles, and organisms. In this communication, a modulation in oxidation/reduction potential via ligation of substrate and protein components in the camphor 5-exo-monoxygenase system is described in terms of a four-state system using as fundamental parameters the transition free energies between equilibrium states. This approach provides a concise description of the data and is useful for describing many aspects of regulatory phenomena.


Ribonuclease H of calf thymus: substrate specificity, activation, inhibition.

When the action of highly purified specimens of ribonuclease H (hybrid nuclease; RNA-DNA hybrid ribonucleotidohydrolase; EC 3.1.4.34) of calf thymus on a wide selection of homopolymer hybrids was studied, the extent, and even the occurrence, of hydrolysis was found to be governed by the interplay of several factors: the composition of the ribo strand, the length of the deoxyribo strand, and the nature of the activating metal. Mn2+ activates the enzymic cleavage of all hybrid combinations, Mg2+ only of those containing purine ribo strands, Co2+ only of poly(A) hybrids. A 1:1 hybrid of phage f1 DNA and RNA is, however, split in the presence of any of these activators. Hybrids with deoxyribo tetranucleotides can still be cleaved, but not with dinucleotides. The behavior of hybrids containing covalently linked runs of ribo and deoxyribopolynucleotides was studied with the hybrid poly(dT)-poly(A)7-(dA)X]. This hybrid is attacked by ribonuclease H so that the bulk of the resulting poly(dA) still retains one covalently linked riboadenylic acid end group, whereas a small proportion carries a ribo dinucleotide. Inhibition studies showed that ribonuclease H is inactivated irreversibly by pretreatment with S-adenosylmethionine at 35 degrees, but not at 0 degrees. S-Adenosylhomocysteine also is inhibitory, but not irreversibly; also it is essentially limited to the inhibition of the cleavage of purine ribo strands. When the enzyme is exposed simultaneously to both inhibitors, irreversible inactivation is diminished considerably.