Synapse and acetylcholine receptor synthesis by neurons dissociated from retina.

Neurons dissociated from chick embryo retina and cultured from more than 1 x 10(8) synapses per mg of protein. At least three types of synapses are synthesized which resemble those of the intact retina. In addition, two populations of neurons were found, those with nicotinic acetylcholine receptors and those without the receptors.


Tubulin aggregation and disaggregation: mediation by two distinct vinblastine-binding sites.

Rat brain tubulin possesses two distinct binding sites for vinblastine per molecule: a high-affinity site with an affinity constant of 6.2 x 10(6) M-1 and a low-affinity site with an affinity constant of 8 x 10(4) M-1. The high-affinity site is labile, with a t1/237 degrees of 3.5 hr, is protected by colchicine, and is unaffected by salt, whereas the low-affinity site is stable but is inhibited by salt. Binding to both sites is rapid. The high-affinity binding constant of vinblastine to tubulin (6.2 x 10(6) M-1) corresponds to the half-maximal concentration of vinblastine needed to prevent polymerization of tubulin in vitro, whereas the low-affinity binding constant (8 x 10(4) M-1) corresponds to the half-maximal concentration of vinblastine required to aggregate tubulin. We conclude that vinblastine binding to the high- and low-affinity sites, respectively, accounts for the depolymerization and aggregation behavior of tubulin.


Comparative study by circular dichroism of the conformation of deazapurine nucleosides and that of common purine nucleosides.

Purine nucleoside analogs modified by replacement of the nitrogen atom at the 3 position by a CH group give a characteristic circular dichroism curve that is not substantially modified by chemical substitution at the 8 position. Since it is rather well established that 8-substituted purine nucleosides are predominantly in the syn conformation in aqueous solution, it follows that the 3-deazapurine nucleosides, whether substituted at position 8 or not, also favor the syn conformation. These data are in sharp contrast to the circular dichroism data obtained on 8-halogenated and 8-alkylated derivatives of adenosine and guanosine, which give circular dichroism profiles substantially different from those obtained on the parent compounds. Certain purine-nucleoside-utilizing enzymes fail to interact effectively with either the unsubstituted 3-deaza analogs or the 8-substituted derivatives of adenosine and guanosine. The hypothesis recently given that the inactivity of the 8-substituted derivatives springs from their syn-conformational preference is tentatively accepted to explain the inactivity of the 3-deaza analogs.


Electrophoretic distributions of human peripheral blood mononuclear white cells from normal subjects and from patients with acute lymphocytic leukemia.

The electrophoretic mobilities of mononuclear white cells from the peripheral blood of normal subjects and leukemic patients were measured. Analysis of both fresh and cryopreserved samples of each type showed that cryopreservation had no distinguishable effect on the electrophoretic distribution of either normal or leukemic cells. Mode mobilities (mobilities at which maximum intensities are observed) of cells from nine leukemic patients were 7-28% below the average mode mobility of normal cells. The standard deviation of the electrophoretic mobilities of normal cells was 2%. Normal cells had an asymmetric, often bimodal, electrophoretic distribution; leukemic cells consistently had a single symmetric distribution.


Charge pair model of bioenergetics: redox enzymes.

A model of electron transfer between redox enzymes is constructed on the assumption that the apoenzyme contains orientable units, which are tentatively identified with flipping amino acids. The model is based on the entatic state hypothesis, and the rate of electron transfer is derived.


Enhancement of postreplication repair in Chinese hamster cells.

Alkaline sedimentation profiles of pulse-labeled DNA from Chinese hamster cells showed that DNA from cells treated with N-acetoxy-acetylaminofluorene or ultraviolet radiation was made in segments smaller than those from untreated cells. Cells treated with a small dose (2.5 muM) of N-acetoxy-acetylaminofluorene or (2.5 J-m-2) 254-nm radiation, several hours before a larger dose (7-10 muM) of N-acetoxy-acetylaminofluorene or 5.0 J.m-2 of 254 nm radiation, also synthesized small DNA after the second dose. However, the rate at which this small DNA was joined together into parental size was appreciably greater than in absence of the small dose. This enhancement of postreplication repair (as a result of the initial small dose) was not observed when cells were incubated with cycloheximide between the two treatments. The results suggest that N-acetoxy-acetylaminofluorene and ultraviolet-damaged DNA from Chinese hamster cells are repaired by similar postreplicative mechanisms that require de novo protein synthesis for enhancement.


Immunological block to mammalian fertilization: survival and organ distribution of immunoglobulin which inhibits fertilization in vivo.

Fertilization of golden hamster eggs was blocked both in vitro and in vivo by antibodies produced in rabbits against specific hamster ovarian antigens (HOA). Antibodies against HOA bound to surfaces of the hamster egg zona pellucida and prevented spermatozoa from attaching to the zona and entering eggs in vitro. Fertilization in animals could be  blocked for four estrous cycles by a single intraperitoneal injection of anti-HOA immunoglobulin, but not by control immunoglobulin. The in vivo fate of anti-HOA immunoglobulin was analyzed by simultaneous injection of 125I-anti-HOA IgG and control 131I-IgG. Both anti-HOA IgG and control IgG appeared in a variety of organs (lung, kidney, spleen, liver, and uterus) shortly after injection, but disappeared rapidly with no detectable differences in organ half lives. However, in the ovary anti-HOA IgG (but not control IgG) persisted at high levels during the period of infertility. Quantitative precipitin analysis of organ homogenates indicated that a high percentage of anti-HOA IgG in the ovary (but not in the other organs tested) was immunologically indistinguishable from IgG indicating lack of radiolabel metabolism and reincorporation. The results are discussed in terms of the development of a specific immunological block to fertility.


Lateral transport on cell membranes: mobility of concanavalin A receptors on myoblasts.

We report measurements of the lateral mobility of fluorescent labeled concanavalin A receptor complexes on the plasma membrane of cultured myoblasts of rat. Transport rates were measured by observing the recovery of fluorescence in a small region of the cell surface initially photobleached irreversibly by an intense, focused laser light pulse. Under different conditions we measured effective diffusion coefficients of the receptor complexes in the range 8 x 10(-12) less than D less than 3 x 10(-11) cm2/sec which is two orders of magnitude lower than we found for a fluorescent lipid probe, D approximately (8 +/- 3) x 10(-9) cm2/sec. This large difference and the presence of apparently immobile concanavalin A receptors suggests that factors beyond the fluoidity of the phospholipid bilayer membrane matrix control the rate of lateral transport of the complexes. Effective mobilities of the complexes decrease with increases in the valence, dose, and occupation time of the lectin on the membrane. These properties imply an aggregation of the lectin-receptor complexes. Mobilities are not influenced by azide, colchicine or preincubation at low temperature. Cytochalasin B and low temperatures, during the time of measurement, decrease the lateral transport rate.


Deficiency of gamma-ray excision repair in skin fibroblasts from patients with Fanconi's anemia.

The capacity of preparations of skin fibroblasts from normal individuals and patients with Fanconi's anemia to excise gamma-ray products of the 5,6-dihydroxydihydrothymine type from exogenous DNA was investigated. The excision capacity of whole-cell homogenates of fibroblasts from two of four patients with Fanconi's anemia was substantially below normal. This repair deficiency was further pronounced in nuclear preparations from cells of the same two patients.


Establishment of a noradrenergic clonal line of rat adrenal pheochromocytoma cells which respond to nerve growth factor.

A single cell clonal line which responds reversibly to nerve growth factor (NGF) has been established from a transplantable rat adrenal pheochromocytoma. This line, designated PC12, has a homogeneous and near-diploid chromosome number of 40. By 1 week's exposure to NGF, PC12 cells cease to multiply and begin to extend branching varicose processes similar to those produced by sympathetic neurons in primary cell culture. By several weeks of exposure to NGF, the PC12 processes reach 500-1000 mum in length. Removal of NGF is followed by degeneration of processes within 24 hr and by resumption of cell multiplication within 72 hr. PC12 cells grown with or without NGF contain dense core chromaffin-like granules up to 350 nm in diameter. The NGF-treated cells also contain small vesicles which accumulate in process varicosities and endings. PC12 cells synthesize and store the catecholamine neurotransmitters dopamine and norepinephrine. The levels (per mg of protein) of catecholamines and of the their synthetic enzymes in PC12 cells are comparable to or higher than those found in rat adrenals. NGF-treatment of PC12 cells results in no change in the levels of catecholamines or of their synthetic enzymes when expressed on a per cell basis, but does result in a 4- to 6-fold decrease in levels when expressed on a per mg of protein basis. PC12 cells do not synthesize epinephrine and cannot be induced to do so by treatment with dexamethasone. The PC12 cell line should be a useful model system for neurobiological and neurochemical studies.


Paradoxical effects of cycloheximide and cytochalasin B on hamster cell hexose uptake.

Cellular regulation of hexose uptake was studied in cultures of NIL hamster cells. Enhancements of galactose uptake were elicited most strikingly by maintaining confluent NIL cultures in culture media devoid of glucose. These glucose-starved cultures showed up to 8- or 9-fold enhancements in the galactose uptake test. When these cultures were treated for extended periods with cycloheximide, the enhanced uptake was left unimpaired, whereas the uptake by glucose-fed cells, similarly treated with cycloheximide, was inhibited greater than 90%. Addition of glucose to these starved cultures resulted in a gradual decline of uptake rates to the unenhanced level (t1/2 approximately 3 hr). In surprising contrast, when both glucose and cycloheximide were added simultaneously, the decline was arrested for at least 12 hr. If cytochalasin B (the specific inhibitor of hexose transport) was present, the uptake of galactose by both starved and fed cells was close to completely inhibited. By several criteria, cells maintained for 24 hr in medium containing both glucose and cytochalasin B were glucose-fed. Yet, when the cytochalasin B was removed, the cells were found to have enhanced rates of galactose uptake. The regulation of the hexose uptake system may therefore not be guided by the levels of glucose catabolites. Alternative mechanisms that may control hexose uptake are considered.


Role of a peptidase in phagocyte chemotaxis.

The potencies of N-formylmethionyl (fMet) peptides as chemotactic agents for phagocytes are related to the rates at which they are hydrolyzed. Furthermore, chloromethyl ketones inhibit chemotaxis as do the products of hydrolysis of fMet peptides. The directed migration of cells in response to such peptides is probably brought about by the binding of the peptide to a cell receptor with subsequent cleavage by peptidase specific for aromatic residues, a process that allows the chemical gradient to be detected.


A purine auxotroph deficient in phosphoribosylpyrophosphate amidotransferase and phosphoribosylpyrophosphate aminotransferase activities with normal activity of ribose-5-phosphate aminotransferase.

Three enzyme reactions have been reported to catalyze the synthesis of phosphoribosylamine in eukaryotic cells. These activities are glutamine phosphoribosylpyrophosphate (P-Rib-P-P) amidotransferase [amidophosphoribosyl-transferase; 5-phosphoribosylamine: pyrophosphate phosphoribosyltransferase (glutamate-amidating) EC 2.4.2.14], ammonia P-Rib-P-P aminotransferase, and ammonia ribose-5-phosphate aminotransferase. A purine auxotroph derived from a cell line  of Chinese hamster fibroblasts was shown to be deficient in catalytic activities of glutamine P-Rib-P-P amidotransferase and ammonia P-Rib-P-P aminotransferase. Extracts from this cell line had normal ammonia ribose-5-phosphate aminotransferase activity. The defect in purine biosynthesis in the mutant cell line was localized to the synthesis of phosphoribosylamine. These results indicate that glutamine P-Rib-P-P amidotransferase or ammonia P-Rib-P-P aminotransferase or both are important for phosphoribosylamine synthesis, but that ammonia ribose-5-phosphate aminotransferase activity probably does not play a significant role in this eukaryotic cell line. The simultaneous disappearance of both P-Rib-P-P-dependent activities suggests these two enzyme activities are closely related structurally or genetically.


Modulation of the immune response by a synthetic adjuvant and analogs.

N-Acetylmuramyl-L-alanyl-D-isoglutamine increases the humoral immune response of mice when given in aqueous media instead of the usual water-in-oil emulsions. Moreover, this compound is adjuvant active even by the oral route. In view of studying the relation between chemical structure and biological activity, several synthetic analogs were tested. The immune response could be modulated according to chemical modifications, and the synthetic analog with D- in place of L-alanine was shown to inhibit the immune response.


Phylogenetic origins of immune recognition: lymphocyte surface immunoglobulins in the goldfish, Carassius auratus.

Membrane immunoglobulin (Ig) of splenocytes and thymocytes of the goldfish, Carassius auratus, was demonstrated by indirect fluorescent-antibody techniques. Observations on shedding and resynthesis indicated that the thymocyte Ig was endogenously produced. The lymphocyte surface proteins were radioiodinated using the lactoperoxidase-catalyzed reaction, and the labeled Ig molecules were isolated by specific precipitation and analyzed by sodium dodecyl sulfate/polyacrylamide gel electrophoresis. The IgM-like membrane Igs of splenocytes and thymocytes were shown to differ in their ease of solubilization with nonionic detergent, and in the sodium dodecyl sulfate/electrophoretic mobility of their heavy chains. The significance of these observations for the evolution of T-cell recognition is discussed.


Interactions between nutritional factors and drug biotransformations in man.

This study was undertaken to examine the influence of nutritional factors on the activity of the mixed function oxidase system in man, which is cytochrome P-450 dependent. Three normal volunteers were fed a low carbohydrate-high protein diet for 2 weeks, followed by a high carbohydrate-low protein diet for the follwoing 2 weeks. At the end of each test diet period, the plasma elimination rates of antipyrine and theophylline were determined. The mean plasma half-life for antipyrine was 17.5 hr on the high carbohydrate-low protein diet and 9.2 hr on the low carbohydrate-high protein diet. The mean plasma half-life for theophylline was 8.9 hr on the high carbohydrate-low protein diet and 5.9 hr on the low carbohydrate-high protein diet. These data demonstrate marked influences of dietary carbohydrate and/or protein ingestion on oxidative biotransformation of drugs in man.


Morphine-like peptides in mammalian brain: isolation, structure elucidation, and interactions with the opiate receptor.

A substance that competes for opiate receptor binding has been isolated from calf brain and identified as two pentapeptides, H-Tyr-Gly-Gly-Phe-Met-OH (methionine enkephalin) and H-Tyr-Gly-Gly-Phe-Leu-OH (leucine enkephalin), with about four times more leucine enkephalin than methionine enkephalin. Sodium and manganese effects on opiate receptor interactions show that both peptides are agonists, whereas leucine enkephalin may be a "purer" agonist than methionine enkephalin.


Tetrodotoxin-resistant dendritic spikes in avian Purkinje cells.

Electrophysiological evidence for the existence of dendritic spikes in the Purkinje cells of pigeon cerebellar cortex is presented. Intradendritic records indicate that the electroresponsive properties of the dendrites linger after voltage-dependent sodium and potassium conductances are reduced by superfusion of the cortex with Ringer's solution containing 20 mug/ml tetrodotoxin and 5 mM 3-aminopyridine. Dendritic spikes could be evoked, in the complete absence of activity from all cerebellar afferents and from the soma and axon of the Purkinje cells, by direct electrical activation of the surface of the cerebellar cortex or by intracellular injection of current via the recording electrode. The denritic electroresponsiveness was blocked by superfusion with 20 mM Mn2+ or Co2+. It is thus concluded that dendrites of Purkinje cells in birds are capable of generating calcium-dependent spikes. The possible role of such a calcium current in neuronal function is discussed.


Chemo-anemotaxis: a behavioral response to sex pheromone in nonflying insects.

The cockroach, Periplaneta americana, running on a Y-ring globe, moves downwind if an air current is directed toward the head. However, if the air current carries sex pheromone, then upwind movement is elicited. This orientation behavior is apparently a mechanism to facilitate the orientation of males searching for pheromone-secreting females.


Radiation therapy in the treatment of leukemic infiltrates of the testes.

Testicular infiltration developed in 6 of 56 boys with lymphoblastic leukemia. All exhibited platelet counts under 100,000, indicating poor prognosis. Patients were treated with vincristine, prednisone, and craniomemingeal prophylaxis (2,400 rads/12 fx) extending to the C2 level. Only 3 patients did not suffer recurrence of testicular disease during their multiple leukemic relapses. Alternate treatment courses are suggested.


[Restoration of hemi-arcades with amalgam].

As a rule should the half-mouth restorations in the frame of oral rehabilitation be done with gold inlays, overlays or full crowns. It is nevertheless possible to consider such restorations with amalgam and, providing that certain principles and technics and respected, such quadrant restorations could be valuable as well on the periodontal point of view as on the occlusal one. Regarding the periodontal point of view, it is now generally accepted that de restorations of the proximal aspects of the teeth have not to extend under the gingival margin. If this creates a risk for caries recurrences, still questionable, it eliminates the unavoidable periodontal lesions. Regarding the occlusal point of view, it is on the one hand difficult to build up a perfect occlusal restoration with a material which, on the moment the filling is completed acquires only a insufficient fraction of its final resistance. On the other hand it seems impossible to raise the occlusion in one or more teeth for the very same reason. The solution to this problem comprises a dubbel aspect. One has first of all to rebuild to the desired occlusal level the cavities of the whole quadrant with a temporary but resistant material wich allows at once a carefulness mastication. Polycarboxylate cement is suitable for this purpose. This temporary material is then replaced tooth after tooth in one or more sittings with amalgam. The second aspect of the solution consists in the use of amalgam wich acquires faster a sufficent resistance, allowing an ajustment of a perfect occlusion without the danger of fracturing it. Following the first estimates it seems that amalgam made of spherical particules and dispersed phase type alloys could meet with this requirements and bring an acceptable solution to our problem.


Urinary fluoride excretion in small children following short-term fluoride supply with tablets or domestic salt.

Urinary fluoride (F) excretion has been studied in small children, with some comparisons with adults, following ingestion of F tablets or fluoridated salt (F-salt) containing 500 mg F/kg NaCl. 24-h urinary F in 7- to 8-year-old children in an institution and in 2- to 12-year-old children in families rapidly increased to average levels of about 0.85 and 0.55 parts/10(6), respectively, when the children had their meals spiced with F-salt. Children in families also showed significantly elevated urinary F excretion with two F-salted meals a day but not with one a day. After taking 0.5 mg F in the form of NaF tablets a group of children without previous F supply attained within 1 d a 24-h urinary F concentration which was about the same as that in children who had been taking caries-preventive tablet doses for years. The percentage of a single F dose excreted in the urine within 4 h after the ingestion of F tablets or an F-salted standard meal was about the same in preschool children and middle-aged adults. F quantities of the order 1.5-2 mg could be ingested by a child eating a meal comprising strongly F-salted dishes, and the urine could reach concentrations around 3 parts/10(6) F during the following 2-4 h. The results obtained support the concept that domestic salt containing about 500 parts/10(6) F is suitable for clinical testing on a larger scale under Swedish conditions. Calculations of F supplies to children aged 2 months-7 years with different diets and water and salt F contents are presented as diagrams.


Fluoride in an experimental cavity varnish.

The aim of the present study was to assess the behavior of fluoride in an experimental cavity varnish. The varnish consisted manily of ethanol and the fluoride was added as a 1 M solution of sodium fluoride. When increasing amounts of ethanol were added to fluoride in water the readings (mV) given by a fluoride ion electrode unexpectedly increased. This effect of ethanol on the readings was less marked at the highest fluoride concentrations. At considerable excess of ethanol, as in the varnish, reproducible readings were obtained. Free fluoride ions corresponding to an effective concentrations of 1 M aqueous fluoride seemed to be present in the varnish. When various amounts of hydroxyapatite were added to the varnish, the fluoride content of the varnish was reduced whereas an increased amount of fluoride was recovered from the apatite.


Sucking habits and occlusion in 3-year-old children.

The material for the present study comprises plaster models of 310 Copenhagen children, impressions for which were taken during the month each child attained the age of 3 years. The occlusion was related to information concerning the child's sucking habits up to the time of the study. The effect of sucking habits of sagittal occlusion was observed in the canine region and the molar region. A higher proportion of distal canine relationships was recorded in children who continued to suck dummies at the age of 3 years than among finger-suckers of children  who have never sucked. In primary second molar region no significant difference was recorded between the various sucking groups. The open bite is clearly dominant among children who persist with a sucking habit.


Root fractures in permanent anterior teeth with incomplete root formation.

A follow-up study was made of seven teeth with incomplete root formation observed in a group of 66 permanent teeth with root fracture. Three fractures were overlooked on the initial radiographs, two other teeth were suspected of being fractured, and an accurate diagnosis was made in two cases only. All teeth exhibited markedly increased mobility at the initial examination, and slight dislocation of the coronal fragment was found in two teeth. Following reduction (two teeth) and fixation (all teeth), the observation period ranged from 1 1/2 to 19 years. Retained pulp vitality, repair in the fracture area and, most important, approximately normal root development with closure of the apical foramen were observed in all teeth. Even the occurrence of re-fracture in two semmingly repaired teeth did not jeopardize the long-term result.


Effectiveness of fissure sealant 3 years after application.

Findings 3 years after the application of a fissure sealant revealed that of the 166 sealed permanent first molars, 7.8% of the sealants were missing or partly missing, 14.5% were in fair condition, and 77.8% had remained in good condition. During the 3-year test period, 7.8% of the sealed permanent molars had become carious, while 63.3% of the respective control teeth had decayed. The teeth which had sealants in good condition showed no caries, whereas 92.3% of the teeth which had sealants missing or partly missing showed carious fissures. The net gain in the study was 104, and the percentage effectiveness of the method was 88.1%. The treatment effect was found to be very significant when analyzed on the basis of homologous paired test-control teeth (P less than 0.001). The sealing of pits and fissures was found to have a positive treatment effect on 60.2% of the subjects when evaluated on an individual basis (0.1 less than P less than 0.05).


Evaluation of a dehydrated test strip,Microstix -Candida for detection of Candida-induced denture stomatitis.

The outgrowth of yeast from the fitting surface of the maxillary denture and the palatal mucosa was estimated in 63 denture wearers by means of smears and by culture on Microstix-Candida (M-C). There was a significant relationship between the concentration of yeasts as assessed by smears and by M-C. There were confluent spots on M-C, indicating large numbers of yeast cells, in 81% of 37 denture wearers with a positive microscopic diagnosis for Candida-induced denture stomatitis, whereas there were confluent spots on M-C in only one of 26 denture wearers with a negative microscopic diagnosis for infection. It is concluded that the M-C test seems to have sufficient diagnostic sensitivity to be an alternative to the smear for establishing the diagnosis of Candida-induced denture stomatitis.


A rapid method for separation and detection of human salivary amylase isoenzymes by isoelectric focusing in polyacrylamide gel.

Human salivary proteins were separated by isoelectric focusing on polyacrylamide gel in flat beds at 1000 V for 40 min. Amylase activity was detected after immersing the gel in 0.4 M tris-HCI buffer pH 7.4 to equilibrate the pH gradient. The enzyme activity was detected after diffusion into an overlayer of agarose gel containing an insoluble dye-starch polymer (Phadebas). Both whole human saliva and parotid saliva from 15 different persons contained four amylase components, except in three cases where only three bands were detected. The bands were all focused within a rather narrow pH range (pH 5.4-7.2) and the results were very reproducible.


Surface potential and adherence of oral streptococci to solid surfaces.

Strains of oral streptococci belonging to the same species but with different zeta-potential adhere with different strengths or become desorbed at different rates. However, strains of various species but with approximately the same zeta-potential also adhere differently. The adherence was found to be affected by the presence of polyvalent of counter ions in the microorganisms studied.


Extremely long duration of chronic myeloid leukaemia with Ph1 negative and Ph1 positive bone marrow cells.

A male patient still surviving 17 years after the diagnosis of chronic myeloid leukaemic (CML) is described. A chromosome analysis of the bone marrow 16 years after the diagnosis revealed 84% Ph1 negative and 16% Ph1 positive cells, all containing the Y chromosome. The disease has been very sensitive to treatment with busulphan but bone marrow hypoplasia has not been induced. It is probable that in some CML patients with such a double cell population the prognosis may be extraordinarily good and that they run a considerable risk of being overtreated due to a pronounced sensitivity to alkylating drugs. Such rare cases should not serve as arguments for aggressive treatment of CML.


Arabinosyl cytosine in chronic myeloid leukaemia: evidence for high cytokinetic sensitivity of myeloblasts.

The effect of a single and of repeated i.v. push dose(s) of Arabinosyl Cytosine (ARA-C) has been investigated in 9 chronic myeloid leukaemia (CML) patients in non-blastic phase. This was done by determining separately the relative compartment size, the mitotic index (IM), and the in vitro 3H-TdR labelling index (IL) of marrow and blood myeloblasts (MB) and promyelocytes plus myelocytes (PMC + MC), before and at intervals after the drug. After a single dose of ARA-C, the IL of marrow MB declines rapidly, and recovers thereafter, often with an overshoot at 15 h. After 2 to 4 doses of ARA-C, the IL of marrow and blood MB rises by a factor of 2 to 3, and is maintained at a plateau during further treatment. The behaviour of the IL of blood MB is not always the same as that of marrow MB. The IM of marrow MB does not rise proportionally to the IL, and sometimes is even found to be decreased. It is suggested that these kinetic perturbations reflect an accumulation of MB in S-phase where many but not all of them are trapped and sooner or later die off. With a few exceptions, ARA-C induces only milder kinetic perturbations in marrow and blood PMC+MC. The overall results of this study are in agreement with the generally accepted mechanism of action of ARA-C (S-phase specific effector agent), and with studies that indicate that the effect of ARA-C depends on the growth pattern and on the degree of maturation of the target cells. It is suggested that a proper evaluation of ARA-C on a cell population should take into account the existence of different cell pools, provided with different proliferative activity and potential, and with variable degrees of maturation.


Acute myeloid leukaemia complicating a breast cancer after mastectomy and radiotherapy.

The author reports a patient treated three years ago for a breast carcinoma. High doses of X-ray had been delivered after radical mastectomy. The possible relationship between this exposure and a rapidly fatal acute myeloid leukemia is emphasized.


G banding analysis of complex aneuploidy in a case of erythroleukaemia.

The chromosomal abnormalities in bone marrow cells from a patient with erythroleukaemia are reported. The complicated pattern of aneuploidy includes 5 marker chromosomes originating from rcp (1;3), t(8;11), t(X;X) and del(7).


Circulating micromegakaryocytes signaling blast transformation of chronic myeloid leukaemia.

A patient with chronic myeloid leukaemia had numerous micromegakaryocytes in the peripheral blood and bone marrow appearing coincidentally with the onset of blast crisis. These cells were initially confused with lymphocytes because of their size, configuration and scanty cytoplasm. The true identification of these cells can be suspected by careful scrutiny of well prepared Wrights stained preparations and proven electronmicroscopically. Such marked dysplasia of the megakaryocyte series appears to be a poor prognostic sign in chronic myeloid leukaemia.


Serial quantitative observations of leukemic and normal hematopoietic cells in the bone marrow of acute leukemia under chemotherapy.

In 87 cases of acute leukemia, leukemic and normal hematopoietic cell count in the bone marrow was serially observed, and the findings were used for evaluating the effectiveness of antileukemic agents and also for determining the grade of decrease in the marrow leukemic cell count required to start the proliferation of normal hematopoietic cells and to obtain complete remission of acute leukemia in adults.


[In vitro studies on the effect of alpha-chymotrypsin on hemostasis].

Postoperative bleeding was observed in 2 patients for whom alpha-chymotrypsin had been prescribed to prevent haematoma or oedema formation. In vitro experiments with citrated blood added with alpha-chymotrypsin evidenced (thrombelastogram, hirudin tolerance test, euglobulin-lysis time) an action on haemostasis. As compared to blanks, the application of an alpha-chymotrypsin dose which was 100-fold higher than those currently used in therapy resulted in a significant shortening of the r-time (thrombelastogram), delayed blood clotting (hirudin tolerance test) and a shortening of the euglobulin-lysis time. In vivo experiments are needed for further elucidation.


[Branchiogenic parotid cysts].

The authors describe 4 cases of branchiogenic cyst of the parotid gland which belong to the rarest developmental disturbances in the region of the first brachial arch. In the first case, there was a cyst formation with articulate surface; the other cysts were solitary ones. In two patients, the upper lobule of gland was removed together with the cyst. In the third case, simple etirpation was performed. In the last case, the posterior part of the parotid gland was resected together with the cyst. The embryological and anatomical acquaintances and the histopathological criteria relating to the diagnosis of this congenital cyst formation are outlined in the present paper.


[Contribution to the clinical picture and hereditary nature of cleidocranial dysostosis].

In the light of 5 cases and of the relevant literature, the author discusses the clinical picture, inheritance and treatment of cleidocranial dysostosis. It is stated that, though the manifestations of cleidocranial dysostosis are varied, this disease is in most cases characterized by a sagittal frontal sulcus with partially closed frontal fontanel and hypertelorism. The author pleady for the regular medical supervision of these patients.


Contribution to the study of chest and lung mechanics in artificially ventilated normal man during surgery.

Firstly the authors describe the principle and the technical application of an original method of measurement of the mechanical ventilatory parameters. Then the method is illustrated with measurements of the pulmonary thoracic and thoraco-pulmonary mechanical parameters in 20 healthy subjects under going extra-thoracic surgery. The results show the lack of correlation between the value of the pulmonary mechanical parameters measured in the awake supine subjects breathing spontaneously and in the anesthetized supine subjects artificially ventilated. The decrease in chest wall elastance could explain the drop in ventilatory level and the unpredictable modifications in pulmonary mechanical parameters. Therefore it is impossible to establish meaningful reference values in healthy subjects undergoing artificial ventilation.


Monitoring respiratory function by computer in ICU. Preliminary work.

The structure of the respiratory monitoring system under construction in Brussels University Hospitals is described. It is modular and hierarchized. It is based on the observation of the lung mechanics, of the flows of inspired and expired gases and of continuous blood measurements in patients artificially ventilated. Respiratory monitoring may be confined to the continuous observation of the natural evolution of a large number of parameters and the extraction of the most possible information with the aid of automatic calculations effected in real time. The authors propose to add deliberate and controlled aggressions of the pulmonary system in order to observe its dynamic behavior. Practical function tests are described. They lead to the calculation of functional residual capacity, continuous distribution of tidal volume, and pulmonary capillary blood flow. These tests can be performed automatically by using a new electronic unit built in our laboratory. It enables a digital computer to control the functioning of a commercially available ventilator.


Recent experience with a respiratory monitoring system in intensive care.

Computer based instrumentation for continuous monitoring of airway flow, pressure, O2 and CO2 concentration offers an improved noninvasive management technique for patients on mechanical ventilators. Computation of these basic signals provides routinely the following measurements: respiratory rate, tidal volume in and out, minute ventilation, positive end-expiratory pressure, mean airway pressure, inspiration-expiration ra measurements, except for O2 consumption and partially for tco2 production. The system works as a monitor of the respirator (detection of malfunction) and as a monitor of the lung function of the patient. It is particularly useful when adjusting the respirator and at time of weaning a patient from the respirator. These maneuvers can be made more safely because they are based on objective measurements and followed by immediate new sets of data. Defining the optimal values of tidal volume and positive end-expiratory pressure has been simplified by the use of pressure-volume plots. A "fighting", is now used as a measure of the severity of "fighting", that is of the effort of the patient to breathe spontaneously while being ventilated. It can detect fighting before it is diagnosed clinically and so can provide a warning that significant physiological changes will occur unless the fighting is controlled. New information about the distribution of ventilation-perfusion ratio can be derived from the expired concentration curve for CO2. Quantitative measurement of the distribution of ventilation shows a very close correlation with clinical events and can be carried out automatically during the normal routine of care of the patient. These on-line quantitative measurements, with the immediate reporting of results, appear to make a positive contribution to patient care.


Essay of any ventilators by means of a pulmonary model with adjustable resistance, compliance and vital capacity.

After a critical study of classic lung models, showing that linear resistances are not faithful nor justified and that pneumotachograph is not a good measuring apparatus because of its inaccuracy (it changes calibration according to the nature of gas mixture and needs integration to determine volumes), authors present their own lung "model". In this model, it is possible to adjust resistance, compliance, vital capacity and residual volume. Parabolic resistances are used, because they more approach physiologic ones. Building of resistances (diaphragms), compliances (rigid tanks with adjustable elements), vital capacity (elastic membrane between two grills) is simple to realise and easy to reproduce. Measures of pressure and volume are given directly by gauges and are insensitive to gas nature, which is important in respiratory physiology. Flow-rates are deducted from volume values. The lung model can be used in a twin-cell shape to show the effects of artificial ventilation in case of pulmonary asymmetry. Examples given underline the interest of having a model with resistances easy to build and an adjustable vital capacity.


Metabolism of estradiol in greyhounds and German shepherd dogs. An investigation with special reference to hip dysplasia.

Metabolism of estradiol was investigated in 5 dogs, 3 female Greyhounds with radiographically perfect hip joints and 2 female German Shepherd dogs with hip dysplasia (one pregnant and the other non-pregnant). One of the Greyhounds was studied both when pregnant and non-pregnant. The non-pregnant dogs were injected with C14-labelled estradiol-17beta i.v. and 5 mg estradiol-17beta benzoate i.m. The pregnant dogs were given only radiolabelled estradiol-17beta. Twenty-four-hour-specimens of urine were collected from the dogs for 6--8 days. Determination of urinary estrone, estradiol-17beta, and estriol was made. It was found that most of the injected estradiol was excreted unmetabolized in all dogs. A significant amount of the injected estradiol was converted to estrone and a small amount to estriol. There was no significant difference in the excretion patterns of estrone, estradiol, and estriol between the Greyhounds with perfect hip joints and the German Shepherds with hip dysplasia, regardless whether the dogs were pregnant or not. The conclusion was drawn that the capacity of dogs with hip dysplasia to metabolize estradiol and to eliminate estradiol and metabolites is not impaired.


Plasma levels of estradiol and plasma protein binding of sex steroids in dogs. An investigation with special reference to development of hip dysplasia in growing individuals.

Peripheral plasma levels of estradiol were determined in 39 dogs of three breeds (Greyhound, German Shepherd, Golden Retriever). Blood samples were collected weekly from 3 weeks up to 17--21 weeks of age. The pups from all three breeds had mean levels of estradiol varying between 4--8 pg/ml. The lowest levels were found in pups which developed hip dysplasia. There was a significant difference (0.01 less than p less than 0.005) between the estradiol levels of German Shepherd pups with normal and dysplastic hip joints. In female Greyhounds, the peripheral plasma levels of estradiol were examined from 17 weeks of age through the first heat. No increase of the estradiol level was seen with increasing age. The ability of dog plasma to bind dihydrotestosterone (DHT) and estradiol was examined in three dogs. It was found that there are at least three types of binding components for DHT: one with high affinity and extremely low capacity, which is heat labile, another which is also heat labile but has a high capacity and low affinity, and a third which appears to be albumin. Estrogen administration to the three dogs lowered the binding of DHT. It was concluded that it is most unlikely that hyperestrogenism is an etiologic factor in canine hip dysplasia. Unphysiologically high doses of estradiol have been used for experimental induction of hip dysplasia. There is a possibility that the levels of plasma proteins, which bind steroids, could be of importance for the etiology of hip dysplasia. A low plasma level of estradiol could be biologically highly significant if there is a low level of a specific binding protein.


Nutrition, weight gain and development of hip dysplasia. An experimental investigation in growing dogs with special reference to the effect of feeding intensity.

Thirty-one dogs from 5 litters with a high parental frequency of hip dysplasia were used in the investigation. Each litter was split in two groups, of which one was put on a high caloric intake, the other one on a low caloric intake. Each member of a group had a paired litter mate in the other group. The litter mates were paired on the basis of the result of a palpatory examination of the hip joints before 12 weeks of age. If possible, paired mates were of the same bodyweight at the time of palpation, and of the same sex. In the groups made up of pups from 3 of the litters, the protein intake was kept at an optimal level, regardless of the amount of calories given. It was found that hip dysplasia was more frequent, occurred earlier, and became more severe in the dogs with a rapid weight gain caused by increased caloric intake than in the dogs which had a low weight gain because of restricted feeding. The final diagnosis was closer correlated with feeding and weight gain than with tightness or laxity of the hip joints before 12 weeks of age.


Development of femoral head to the rat from calcification to ossification.

The development of the epiphysis of the femoral head from calcification to ossification was investigated in 50 rats of Wistar strain from an age of 10 to 63 days using radiography and histology. The first deposition of calcium in the cartilage appeared in the central portion of the epiphysis at an age of about 21 days. The region of calcification gradually expanded toward the periphery and after about 3 weeks it occupied the entire epiphysis except for the periphery. After completion of calcification ossification began in the lateral part of the epiphysis at the earliest at an age of 6 weeks. The onset of ossification was characterized by disintegration of hypertrophied cartilage cells and formation of bone trabeculae accompanied by vascular invasion from the lateral side.


Normal and estradiol induced calcification of the femoral head in rats.

It was found that calcification of the femoral head epiphysis occurred earlier in the female than in the male rat. Administration of estradiol lead to earlier appearance of calcification in both sexes.


Estradiol induced skeletal changes. The long term effect of prenatal and postnatal administration in beagles.

Beagle pups were injected with 200 mug estradiol benzoate per kg body weight daily 5 times weekly during the first 8 weeks of life. The skeletal development of the pups was followed from 8 weeks to 18 months of age. The femoral heads were smaller and the hip joints more unstable in these pups than in controls from 10 weeks of age. The femoral head ossification center increased more rapidly in size in these pups. The bone mass was also increased. Pups of pregnant bitches, which were injected with estradiol benzoate during the last three weeks of gestation, were studied. The highest total dose injected to the bitches was 90 mug per kg bodyweight. Changes in the hip joints such as small femoral heads and increased instability were found in these pups at 8 and 10 weeks of age. Bone mass was less in these pups than in controls. In adult life these pups had loose hips but they did not develop the complete picture of hip dysplasia. The present investigation demonstrates that the early changes in the hip joints caused by estradiol lead to hip dysplasia.


Growth and mitotic rate of the proximal tibial epiphyseal plate in hypophysectomized rats given estradiol and human growth hormone.

Hypophysectomized female immature albino rats were injected with HGH, HGH and estradiol, or estradiol solely. Some animals were left as controls. All animals were killed on day 3 or 5 of the experiment. One hour before sacrifice, the animals were flash labelled with tritiated thymidine. The following parameters were registered: labelling index, thickness of the growth plate, weight gain, and size of the uterus. The following conclusions were drawn. 1. Estradiol decreases the mitotic rate and retards growth of the epiphyseal cartilage. Its effect on the mitotic rate is more pronounced than its effect on the thickness of the tibial epiphyseal plate. 2. HGH increases the mitotic rate and promotes growth of the epiphyseal cartilage. Its effect on the thickness of the epiphyseal plate is more pronounced than its effect on the mitotic rate. 3. Estradiol decreases the mitotic rate even in the presence of HGH. 4. Estradiol seems to have a direct effect on mitosis of the chondrocytes.


Growth and remodeling of the hip joint and proximal femur in adolescent dogs. A scintimetric investigation with special reference to hip dysplasia and estradiol induced changes.

The uptake of 85Sr was shown to be higher in dysplastic hip joints than in normal joints of adolescent dogs. This was interpreted as a sign of increased remodeling. In contrast, the uptake of 85Sr in the growth plate and metaphysis of the proximal femur was lower in dogs with hip dysplasia than in dogs with normal hip joints. This was interpreted as a sign of retarded growth of the proximal femur (more advanced skeletal maturation). Greyhounds of bitches, which were injected with estradiol during pregnancy, also showed retarded growth of the proximal femur. This was interpreted as a late effect of estradiol.


Skeletal development of greyhounds, German shepherd dogs and their crossbreed offspring. An investigation with special reference to hip dysplasia.

Skeletal development (appearance of secondary ossification centers) of Greyhounds, German Shepherds and their crossbreed offspring was studied. It was found that Greyhounds were more mature at birth than German Shepherds. Crossbreeds held an intermediate position. After about 16 weeks the skeletal age of German Shepherds was more advanced than that of Greyhounds and Crossbreeds. Of 28 German Shepherds which were radiographed at 6 months of age 6 (21%) had hip dysplasia. Four of these were sacrificed and necropsied together with 3 radiographically normal litter mates. These "normal" pups had incipient macroscopic and histologic signs of hip dysplasia. All Greyhounds and Crossbreeds, which were radiographed at about 6 months of age, had normal hips. Three Greyhounds and 7 Crossbreeds were necropsied at 6 months of age. Their hip joints were normal. All German Shepherds had unstable hips (post mortem) from an age of 4 weeks while Greyhounds and Crossbreeds had stable or only slightly unstable hips. On the basis of previous experiments with estradiol induced hip dysplasia it was suggested that German Shepherd are under influence of more maternal estrogens during fetal life than Greyhounds and Crossbreeds. The accelerated skeletal maturation and early sexual maturity of German Shepherds indicate an early and/or higher production of endogenous estrogens, which retards growth of cartilage, initiating the vicious circle of hip dysplasia. It was concluded that investigations of estrogen levels and further studies of skeletal development of dogs with and without hip dysplasia are necessary before any definite conclusion on etiology and pathogenesis of spontaneously occurring hip dysplasia can be drawn.


Optimizing anterior and canine retraction.

Vertical loops or modified vertical loops are basically frictionless springs which are used for canine and anterior tooth retraction. The design and selection of a proper loop or retraction spring should be based on a number of scientific criteria. Foremost among these would be a sufficiently high moment-to-force ratio so that root apices are not displaced mesially or anteriorly. A retraction spring with zero angulation of its horizontal-occlusal arms delivers a moment when activated to produce a force. The ratio of this moment and force is constant throughout the elastic range of activation of the spring. The higher the moment-to-force ratio, the greater is the clinician's control over the apices of the anterior teeth. An analysis of design factors demonstrates that the higher the loop occluso-gingivally, the shorter its horizontal length occlusally, and the greater the gingival horizontal length as in a T loop; these are significant factors in increasing the moment-to-force ratio. The placement of helices is a useful design consideration but the main effect is in reducing the load-deflection rate. By keeping these design factors in mind, the clinician can build into his retraction springs, without the placement of any gable bend, the largest possible moment-to-force ratio so as to optimize his tooth movement. Although it may be possible to design retraction springs to deliver an adequate moment-to-force ratio for controlled tipping around the apex of an incisor or a canine, translatory movements are not possible, considering the intraoral limitations on spring height. This can be overcome by the placement of gable bends or angulation in a vertical loop or retraction spring. Unfortunately, with the typically used high-load-deflection-rate vertical loops, activation to achieve the desired moment-to-force ratio is too critical, exacting, and changeable with small displaced movements of the tooth. This can be partly overcome by utilizing designs that have not only the highest possible moment-to-force ratio during pure horizontal activation of their arms but low-load deflection rates as well. Because of the low load-deflection rate, moment-to-force ratios are relatively more constant if a gable bend (angulation) is placed. The science of spring design as applied to the problems of canine and anterior tooth retraction in this article allows the clinician to optimize the design of his retraction springs. More important, with properly designed springs, it allows him to estimate with relative accuracy the force systems produced and to avoid undesirable side effects which might not have been apparent from superficial observation.


Reconstitution of the human oxytalan system during orthodontic tooth movement.

Orthodontic tooth movement in man has revealed that the oxytalan fiber system possesses a high order of maintenance. Oxytalan fibers did not merely increase in number during orthodontic movement. On the contrary, the oxytalan fiber system underwent reconstruction and adaptation to extensive metabolic and anatomic changes within the periodontium. With the use of light orthodontic forces, the oxytalan fiber system was constantly remodeled on both the tension and compression sides and maintained a characteristic cementum-vascular relationship even when teeth were moved a significant distance through the alveolar bone. In contrast, heavier forces caused localized destruction of the oxytalan system in regions of excessive pressure and tension. Reconstitution of the oxytalan system provided evidence against the concept that oxytalan fibers are stretched by orthodontic movement and subsequently contribute to relapse by elastic rebound. In man the oxytalan fiber system  of the periodontal ligament is arranged as a three-dimensional fiber meshwork and exhibits a complex geometry like other fiber systems in the connective tissues. Knowledge of the interaction between elastic and collagen fibrillar assemblies has been used to derive some speculative concepts of oxytalan-collagen interaction. These concepts have been put forward with the intention of stimulating further interest in the oxytalan fiber meshwork. The present investigation emphasizes that the use of the light microscope to examine and record static images of complex biologic changes can provide new knowledge of the structure and function of human connective tissues.


Early orthopedic treatment for class III skeletal patterns.

Early short-term use of the chin cup resulted in the following significant findings in Class III skeletal problems: 1. A decrease in the gonial, mandibular, and SNB angles. 2. An increase in posterior facial height as a result of increased ramal height. 3. A faster and more pronounced result in the younger patients. 4. Correction of the Class III malocclusion. These findings negate the idea that Class III traction simply repositions the condyle within the fossa. When tracings are superimposed, it is obvious that these changes are not that of a rigid body. It is believed that the change is due to remodeling of the mandible itself. The shape changes as a result of the extrinsic mechanical forces plus the intrinsic functional requirements of the newly determined position. The question as to what degree the new functional homeostatic relationship can overcome the genetic aberration of a more forward-growing mandible. This conflict will probably vary with each individual and may be predictable in the near future. However, should the aberrant growth manifest itself, it would simply require renewed force application.


Vertical control: a multifactorial problem and its clinical implications.

In this article we have tried to analyze the importance of vertical control in orthodontic cases, as well as the factors affecting it. From the cases presented, it can be assumed that: 1. In vertically growing or nongrowing persons (high-angle cases), the application of proper directional forces becomes extremely critical because a clockwise rotation of the mandible can occur very promptly and is very undesirable. 2. In cases with favorable growth potential, the results may be acceptable, even if the forces applied during treatment are not absolutely controlled; in other words, Mother Nature may often compensate for inappropriate or miscalculated treatment procedures.


Occlusion and orthodontics.

The importance of considering the functional aspects as well as the static concepts of an occlusion was demonstrated in the case of an 11-year-old girl with postorthodontic temporomandibular joint muscle pain dysfunction. The following characteristics of an ideal occlusion were discussed as they relate to the entire masticatory system: 1. There should be no slide in centric; that is, there should be a stable jaw relationship when occlusal contact is made in centric relation closure. 2. There should be freedom in centric, that is, freedom for the mandible to move from centric relation to centric occlusion and slightly anterior to centric occlusion without interference. 3. Centric relation should be at the same contact vertical dimension as centric occlusion. 4. There should be no buccolingual thrust or impact to any tooth on closure to contact in centric relation or to centric occlusion. 5. Between centric relation and centric occlusion there should be an unrestricted glide with maintained occlusal contact. 6. Complete freedom for smooth-gliding occlusal contact movements in various excursions from both centric occlusion and centric relation. 7. Occlusal guidance should be on the working or functioning side rather than on the balancing or nonfunctioning side. 8. There should be no soft-tissue impingment from occlusal contacts. In effect, the occlusion should be related to centric relation and centric occlusion prior to, during, and at the completion of active treatment. The final occlusion should provide unhindered closure in centric relation, smooth-sliding lateral and protrusive movements, and an optimal bilateral vertical contact dimension. Orthodontic treatment must include proper occlusal adjustment procedures to obtain the goals of an ideal occlusion in most instances.


Clinical experiences with circumferential supracrestal fiberotomy.

This article has reported on a survey of 1,000 randomly selected orthodontists in the United States to ascertain the incidence of use of the circumferential supracrestal fiberotomy technique to minimize rotational relapse. It was also the purpose of the study to determine whether any problems were associated with the procedure. While the surgical technique is not widely prescribed, there are regional differences. The result of this survey tend to indicate that the technique is reasonably problem-free and that its use probably will be increasing in the future. It should be emphasized that quantitative long-term studies of the effectiveness of the procedure and of possible periodontal sequelae have to date not been reported in the literature.


Interrelationships between orthodontics and periodontics.

At the present time, periodontists have no evidence to indicate that orthodontic treatment in the child will either enhance or detract from the periodontal health of the patient or that it will increase or decrease the longevity of the teeth. Many periodontists believe that much orthodontic treatment is undertaken on an esthetic or empirical basis. Proper emphasis on plaque control procedures prior to initial banding, altered and reinforced during the entire period of orthodontic treatment, may well minimize the inflammatory lesion often found during therapy. Gingival, periodontal, and mucogingival problems should be treated as soon as they are diagnosed. Limiting our orthodontic objectives in adult patients because of the possibility of inducing supporting alveolar bone loss and other problems that did not previously exist may be a worthwhile compromise. Orthodontic movement in periodontally healthy adults, and especially in those with periodontally involved teeth, constitutes a problem distinct from routine orthodontics. When periodontal disease has already produced significant destruction of supporting tissue and secondary occlusal trauma is a complicating factor, orthodontic treatment may possibly serve as another mode of treatment to reestablish the correct occlusal plane and alter bony deformities. Various methods can be used to try and place teeth into better bone. One should make certain that teeth are being moved into a greater volume of bone. The bite plane is of great value in allowing continuous eruption of the teeth and their supporting structures and in eliminating additional trauma by enabling the teeth to move into their correct cusp-fossa relationships unimpeded by the inclined planes of the opposing teeth. Since little is known about the interrelationships between orthodontic treatment and periodontal health and disease, there is still a great deal to learn. In spite of this lack of knowledge, the general practitioners and the various specialists of dentistry, each seeking a rationale for his preventive and therapeutic procedures, subject the patient to treatment based on concepts of the occlusion which have yet to be corroborated. In addition to the need for research in this field, a common language between the periodontist and the orthodontist must be established to eliminate the existing communications barrier. Once basic principles can be determined, elucidated, and applied correctly, the movement of teeth in periodontal cases will be limited only by the imagination of the operator.


Application of the "Wits" appraisal.

The "Wits" appraisal is intended as a diagnostic aid to be used in conjunction with other analyses. Whereas the popularly used ANB angular reading is a simple method of measuring degree of jaw disharmony, there are many instances in which this reading is suspect. The "Wits" appraisal permits easy identification of these shortcomings and substitutes a reasonably reliable means of measuring extent of anteroposterior jaw disharmony.


Use of a submental-vertex analysis for producing quality temporomandibular joint laminagraphs.

A radiographic analysis which can be used to produce high-quality laminagraphs of the temporomandibular joint has been presented. Submental-vertex radiographs of twenty-six dry skulls and fifty vital subjects were used as the sample. Statistical examination demonstrated a wide range of condylar angulations and midline-to-condyle distances. These two measurements are critical to the production of laminagraphs used for pathologic diagnosis of TMJ dysfunction. The results of this study seem to verify the need for an accurate method of determining these two influential quantities.


A follow-up of 78 patients with Gilles de la Tourette's syndrome.

The authors conducted a follow-up study of 78 patients with Gilles de la Tourette's syndrome. Four of the patients were in spontaneous remission; 59 patients taking haloperidol showed an average improvement of 79.3% and the remaining patients, 3 of whom were taking medication other than haloperidol and 12 of whom were not taking any medication, showed an average improvement of 24.7%. Side effects were the main cause of discontinuing haloperidol. The authors found that response to haloperidol was unrelated to family history of tics, age at onset, type or severity of symptoms, or signs of organicity.


Fluidic technology. A discussion and a description of a fluidic controlled ventilator for use with high flow oxygen techniques.

The principles of fluidic technology are outlined and applied in the description of a fluidic controlled ventilator. The device is compact, easy to operate and practically fail-safe since it has no moving parts. There is a sensor which prevents any increase in airway pressure above the preset level.


[Control of respirator pressure and drainage of the anesthetic gases with Kuhn's device in pediatric anesthesia (author's transl)].

By adding a manometer and a pressure valve to the anaesthetic equipment used for newborns and children (Ayre-T-piece, modified by Kuhn) we are able to control airway pressures continuously and to draw out all narcotic gases from the operating room. The concentration of halothanee thus can be diminished to a very low level around the aneasthesist and the surgeon.


[Neonatal leukemia. Report of seven cases (author's transl)].

No more than 150 cases of neonatal leukemia had been reported in the literature. Seven additional cases are reported herein. The incidence of neonatal leukemia has been of one in 50,000. Its incidence among the group of neonates requiring hospitalization has been of 0.075%. The seven neonates with leukemia consist of five males and two females. Two of them had an associated Down's syndrome. Abdominal distension, hepatomegaly, splenomegaly, cutaneous manifestations and purpura were the most frequent clinical findings in our patients. Severe anemia was present in only three patients. Thrombocytopenia was recognized in six of them. A high white blood cell count was present in five patients. The number of blast cells in their peripheral blood smear ranged between 16 and 100%. A remarkable myeloid dominance was observed. One patient died two hours after birth and his diagnosis was made at autopsy. Three patients were diagnosed before the age of three weeks. The three patients with myeloid leukemia were treated with DNR and Ara-C. A complete hematological remission was achieved in two of them. One patient died of a Pn. carinii pneumonia one month after the remission was induced. The remainder patient of this group had a Down's syndrome and the leukemia had been confirmed by hepatic biopsy. After two years of maintenance with Ara-C and Thioguanine he is alive and both, peripheral blood and bone marrow, remains normal. A lymphocitic leukemia was seen in only two patients. One was treated with prednisolone and VCR, and the other with prednisolone, VR and L-Asp. In both cases a good response to the chemotherapy was observed. Autopsy was performed in all patients who died but one. The pathological findings are analyzed. The low survival among patients with neonatal leukemia may be influenced by the toxic side effects of the used chemotherapy. All aspects of the medical treatment including drugs of choice and the usefullness of isolation devices are further discussed.


[Myelomonocytic leukemia in childhood (author's transl)].

Report of five cases of juvenile myelomonocytic leukemia; authors describe an hemopathy of the young child with important splenomegaly, hepatomegaly and adenopathies; anemia with erytroblastemia; hyperleucocytosis with myelemia and monocytosis, rich and granulous bone marrow. Also remarkable is evolution, as it fatal outcome often occurs before a two year evolution, without remission looking like acute myeloblastic leukemia, a few patients have remission of most the symptoms, ending in an apparent recovery, which may be spontaneous.


[Acute lymphoblastic leukemia an pericarditis (author's transl)].

In a brief communication a case of acute lymphoblastic leukemia is presented, of which the principal characteristics were: 1) An exceptional onset due to its pleuropericardial manifestations while the hemogram was normal. 2) A quick terminal evolution after a short and total remission. As far as authors know in Spain, this localization has never been described primarily and in consulted bibliography the appeared cases were always found in older patients. We call attention to the pericardial effusions of a large volume in children in which the diagnosis of classical pericarditis can't be quickly detected.


[Acute lymphoblastic leukemia: treatment results in 27 children (author's transl)].

Therapeutic protocol and treatment results of 27 children with acute lymphoblastic leukemia are described. A remission rate of 88 per 100 was obtained. Fourteen children are living. Five of those followed for two or more years are living (35 per 100). The prophylaxis of leukemic meningitis was done with intrathecal Methotrexate. Only one child treated in this manner developed leukemic meningitis. Infection was the most frequent cause of death.


[Acute lymphoblastic leukemia. Study on 34 children (author's transl)].

Study on 34 children among two and five years old affected by L.L.A. and 37 with different kind and differently localizated tumours is presented. Children affected by L.L.A. are distributed in two groups which followed a different therapeutical attitude. Clinics, cytochemistry, evolution and survival possibilities as well as the response to different therapy and inversion of L.L.A. relation with tumours during the last years.


[Factors influencing outcome in children with acute lymphoblastic leukemia (author's transl)].

Several factors such as age, sex, cytological type, visceromegaly, blast cell count in peripheral blood and recently some immunological traits, have been incriminated by some authors as having a variable prognostic value. Hypothetical influence of some of these factors on the rate and duration of the complete remission in an homogeneous group of 61 children with acute lymphoblastic leukemia have been studied. All of them were treated with same schedule (C protocol) in order to eliminate therapy influence. Some differences, without statistical significance, have been found related to: A) Sex: Mean duration of complete remission has been longer in females. B) Blast cell count in peripheral blood: Patients with initial blast-cell values under 25.000/mm3 have shown an increased number of complete remissions and a longer duration of the complete remission. No relationship has been found between initial age or visceromegaly and duration of complete remission. Neither, no relationship between cytomorphologic type and rate and duration of the complete remission could be established in our series.


[Duration of chemotherapy in acute lymphoblastic leukemia of childhood (author's transl)].

Most of criteria on duration of chemotherapy in acute lymphoblastic leukemia of children are based upon the prolonged state of complete remission (CR). Twenty five cases of 30 months CR duration were studied for their follow-up. Maintenance therapy in these patients was made according to two modalities. The first one was a cyclic single therapy with no prophylactic CNS treatment and the other was a combination chemotherapy method including periodical reinductions and i.t. administration of methotrexate. Most of the 30 month remissions (twenty) were attained by the last method. Until now evolution of the 25 patients has been as follows. Two died, being in CR, by infectious diseases. Eleven more suffered relapses, most of them in the following year. The other twelve patients remain in the initial CR. Chemotherapy was supressed in 10 patients (in seven at 36 months and in three at 48 months) starting then BCG immunotherapy. Three of these children suffered relapses a few months after suppression. Seven others are in remission of 47 months median duration. In other five patients, chemotherapy was not interrupted. Two died by infectious diseases and other three have relapsed. Even though the experience is too short in order to establish any conclusion, results obtained until now appear to favor suppression of chemotherapy after 30 to 36 months in patients remaining in CR.


[Pulmonary complications of leukemia in children. A study of 72 cases (author's transl)].

A study was made of 72 cases of leukemia in children (the majority of which were acute lymphoblastic in type or with undiferenciated cells), in order to examine the type and frequency of pulmonary complications in leukemia, once complications of infectious etiology had been rejected. Pulmonary complications were found in 23 cases. Most often recurring image was the disseminated reticulonodular type. Nodular images and diverse pulmonary infiltrates were also discovered, these were often peribronchial and bilateral in almost every case. No significant relationship was found regarding the age of children, type of leukemia or length of time illness took to develop. Finally, present increase in the frequency of pulmonary complications in leukemia is commented and possible etiologic part antiblastic therapy might play on certain occasions is speculated.


[Pulmonary disease during mtx therapy in a.l.l. (author's transl)].

Authors describe three cases of pulmonary disease showed in three children with acute lymphoblastic leukemia during maintenance therapy with Methotrexate (MTX) (Dose: 30 mg/sm/W). The initial symptom occurs in the lapse between 40 and 135 days within the first MTX maintenance period and in 35 days in the second maintenance period. Leukopenia with eosinophilia (192-264 eosinophils/mm3) occurs in case 1. The maintenance of the MTX therapy in this case ends with death of the patient. Radiological studies show basal bilateral pulmonary infiltrations, with pleural involvement in one case. Authors insist in the drug (MTX) suppression as main therapy and agree with the opinion of some authors concerning to the 31 cases previously published.


[Uric nephropathy in malignant hemopaties: three cases with conserved diuresis (author's transl)].

Three observations of acute hyperuricemic renal insufficiency with conserved diuresis appeared during the course of a citostatic treatment of a lymphoblastic acute leukemia and two lymphoblastic lymphosarcomas are studied. The evolution of nephropathy was favourable in all cases by means of allopurinol and fluidtherapy.


[Hypercalcemia in acute lymphoblastic leukemia (author's transl)].

A case of acute lymphoblastic leukemia that appeared as hypercalcemia with radiologic osseous abnormalities and back pain is described. Pathophysiologic mechanisms of hypercalcemia and treatment are reviewed. After initial treatment with phenobarbital and saline solutions, followed by specific treatment for the leukemic process, hypercalcemia descended to normal values.


Development of CNS leukaemia in acute myeloid leukaemia in childhood.

In 130 cases of acute myeloid leukaemia in children below the age of 14 years in Great Britain, there were 21 cases in which the central nervous system was involved. The incidence and timing is similar to that of acute lymphoblastic leukaemia; in a small number of patients who received prophylactic treatment, involvement of the central nervous system was prevented.


Multiple major cerebral artery thromboses with profound thrombocytopenia in acute leukaemia.

A child with acute lymphoblastic leukaemia complicated by prolonged gastrointestinal and skin haemorrhages due to profound thrombocytopenia finally died of thrombotic occlusions of major cerebral arteries due to mucormycosis. Biopsy of any suspect lesion is needed urgently before prolonged therapy with amphotericin B is started. So far there have been no cures in childhood.


Loiasis. Report of a case and review of the literature.

An adult worm was isolated from the left upper eyelid of a man, eight years after he had left an area in which L loa is endemic. We described his case in order to draw attention to some differences between reported features of the disease in areas in which the worm is endemic and in areas in which it is not.


[Induction of phagocytosis by immunotherapy against leukemic leukocytoblasts].

Since 1975, the authors have been working in immunochemotherapy in acute myeloblastic leukemic adult patients. Autologous leukemic leucocytoblasts have been cultured with Vibrio cholerae neuraminidase (NVC). Thereafter, neoplastic cells were radiated with cobalt bomb and frozen to--70degreesC and afterwards 5 X 10(6) of these leucoblasts were intradermally injected to each patients every eight days. All patients received between six to ten injections. So far, ten such patients have been followed during eight months and since two months after immunization no leukemic leucocytoblasts in bone marrow and blood have been detected. Hemoglobin and platelets have increased more rapidly than usual and no patient has developed side effects. Phagocytosis tests carried out in vitro during remission, have demonstrated that only in immunized patients neutrophils and monocytes were capable of phagocytosis of autologous cultured malignant leucocytoblasts. The nucleus of phagocytized malignant cells was small and basophylic. These so far undescribed phagocytic cells were named post-immunization cells.


Rectal biopsy in type 4 glycogenosis. An ultrastructural cytochemical study.

Rectal biopsy material from a patient with type 4 glycogenosis was studied by ultrastructural cytochemical methods. The diagnosis of the disease was made on the basis of the patient's clinical history, the autopsy findings, and the histopathological features. Numerous large macrophages were observed in the rectal mucosa. They contained large vacuoles filled with filamentous material and small granules. This amylopectin was stained by the Thiery method (periodic acid-thiocarbohydrazide-silver proteinate) after 18 hours of exposure to thiocarbohydrazide; only 30 minutes was sufficient to demonstrate seemingly normal beta-glycogen particles in epithelial cells.


[Treatment and prognosis of osteosarcoma in childhood (author's transl)].

126 osteosarcoma under the age of 15 years are followed up in an interclinical study. There is a steady increase of tumor incidence towards the 15th year with a slight male preponderance. The main sites of the tumor are the distal femur followed by the proximal tibia and humerus. Evidence of multiple metastases is most often present in the lungs, less often in the skeleton. Nearly always metastases became evident within 2 1/2 years after diagnosis (98%). Therefore the 2 1/2-year disease--free survival rate seems to be sufficient for prognostic evaluation. The over all 2 1/2-year survival rate was 17,5%. Though the different methods of treatment are not statistically valid, the best results can be expected after early amputation. By radiotherapy alone no cure has been achieved. Survivals were seen at any age and at any site of long bones (distal femur, proximal tibia, humerus, femur, distal radius). Prognosis of osteosarcoma in the childhood is similar to that of the adult group.


[Results in the treatment of acute leukemias at the Internal Clinic B in the period 1970-1975].

Results of the treatment of 102 acute leukemia patients are presented. The diagnosis in 61 patients was acute myeloid leukemia (AML) and in 41 patients acute lymphoid leukemia (ALL). In the treatment of AML were used Daunorubicyne (DNR), Cytosine arabinoside (ARA-C) or combination of both drugs, some elder patients being treated with 6-mercapropurine. Number of patients were made aplastic and died during the initial phase of therapy. Nine of 24 patients treated with DNR, ARA-C or combined developed complete remission, 6 patients lived for one year and 4 patients two years. ALL patients were treated with Prednisone-Vincristine, Prednisone-Vincristine-DNR and some of them with Prednisone-Vincristine-DNR-Cyclophosphamide-L-Asparaginase combinations of drugs. Complete remission was obtained in 22 out of 32 patients (69%) and 6 patients lived for 2 years.


[Combined cytostatic therapy in the treatment of acute leukemias].

It was analysed 66 patients with different types of acute leukaemias treated on haematological department of Internal Clinics Mylitary Medical Academy during 1969-1974 years with combination chemotherapy. At 35 patients with acute lymphoblastic leukaemias it was obtain complete remission at 60%, and partial remission at 28,5%. Without the response was 11,4% patients. At 20 patients with acute myeloid leukaemias were induced only partial remission at 4 0% patients, and 60% patients were without the therapeutic response. The survival of patients with acute leukemias is presented. 88,4% patients with acute lymphoblastic leukaemias survived to two years, and 61,5% patients with acute myeloid leukaemias survived only to three months. None of the patients with acute myeloid leukaemias survived over one year.


[Treatment of acute leukoses at the Internal Clinic of the Dr. Z. Kucic Hospital in Rjeka].

The offects of treatment achieved in 35 patients with Acute Leukemia have been presented. In the group of 10 patients with Acute Lymphocytic Leukemia remission have been obtained in 9 patients with the mean survival of 13,7 months. In the group of 25 patients with Acute Nonlymphocytic Leukemia remissions have been obtained in 16 patients with the mean survival of 9, 6 months.


[Treatment of acute lymphocytic leukemia in children with combination chemotherapy and irradiation of the central nervous system].

From July 1972 until April 1975 51 children with acute lymphocytic leukemia had been treated with combination chemotherapy and central nervous system irradiation. First remission was induced in 46 patients. 13 patients died during the first and second year of treatment. Central nervous system leukemia developed only in 3 patients. In 9 patients chemotherapy had been stopped after 30 months of treatment. These results are very encouraging and we hope that majority of our patients will survive 5 years without relapse.


[Results in the treatment of acute lymphoblastic and acute myeloblastic leukemia in children (using Pinkel's and Clarkson's schedules)].

At the Center for the study and treatment of leukemia in childhood (Ward of Hematology, Department of Pediatrics Salata Zagreb) children with acute leukemia are treated by a combined therapy consisting of corticosteroids, chemotherapeutic agents and subjected simultaneously to radiotherapy. The authors present the results achieved in 40 children with acute leukemia (during the period from March 31, 1973 to March 31, 1975.) randomly distributed into three groups. Each group was treated according to a different protocol (using Pinkel's modified scheme for ALL and that of Clarkson for AML), with or without profilactic irradiation of the CNS.


[Our experiences in the treatment of acute leukemias].

This paper deals with observations concerning treatment of acute leukemia in the Department of haematology of The Clinical hospital of Belgrade during the period from 1970 to 1975, and with results of the treatment itself. During the last five years, 27 patients with different types of acute leukemia were treated. The type of acute leukemia was determined using cytological criteria of Levy and Lortholary and cytochemical criteria as described by Hayhoe. One thrid of the patients died during the first days of hospitalisation, before any effect of cytostatic treatment could be evaluated. The cause of death in those patients was septic shock, intracranial haemorrhage or cardiovascular colapsus; initial signs of those complications of acute leukemia were allready present before diagnosis. Those data point to the fact that diagnosis of acute leukemia is often made too late, when irreversible ocmplications of the disease are allready established. Patients over sixty, often "fragile" to aggresive cytostatic therapy, may enter complete and relatively long lasting remission with induction therapy cosisting of 6-mercaptopurine and methotrexate only. Allthough the number of cases was rather limited, the authors had rather disappointing results with the 06-LA-66 protocole in adult lymphoblastic leukemia. The first with COAP treatment protocole seem encouraging. Adequate cytostatic therapy was in several cases impossible, duo to the lack of adequate substitution therapy; such inadequate cytostatic therapy resulted in partial remissions with a rather poor quality survival. A beeter cooperation is needed between hospital centers and institutions which provide matherial for the substitution theapy.


[Treatment of acute leukemias].

A review of the current attitude and the possibilities of the treatment of acute leukemias are presented. The basic principles of the treatment of different forms of acute leukemias are pointed out. A review of chemo-therapeutic devices which, most often joined together, are used nowadays in the treatment of acute leukemia is presented. The importance of the application of corresponding cytological and cytochemical methods for the separation of the acute lymphoblastic from the acute non-lymphoblastic leukemias is underlined, with regard to different ways of treatment and different reactions to the polycytostatic treatment. The mechanism of action of various cytostatics drugs is presented. The need for the simultaneous use of several cytostatics is underlined in order to achieve remission in as many patients as possible. At the end the authors underline the importance of the immunotherapy and of its future application in the treatment of acute leukemias and malignant neoplasms.


Acquired resistance to daunorubicin in a patient with acute myelogenous leukaemia.

Measurement of in vitro and in vivo resistance to daunorubicin in AML patients suggests that there is no simple correlation between the two. In a patient who became clinically resistant and whose cells showed a parallel increased resistance in vitro we found the acquisition of multiple drug resistance. The increased in vitro resistance to daunorubicin could to some extent be overcome by conjugating daunorubicin to DNA.


The cryopreservation of leukaemia cells: morphological and functional changes.

Stored autologous haemopoietic cells may be used to repopulate the bone marrow of patients in the advanced stages of different leukaemias who have received cytotoxic drugs. We have used a continuous flow blood cell separator to collect peripheral blood leucocytes from patients with chronic granulocytic leukaemia (CGL) before treatment. We also collected bone marrow cells from patients with CGL and from patients with acute myeloid leukaemia in complete remission. The collected cells were frozen at I degree C per minute using dimethyl sulphoxide as cryoprotective agent and stored in liquid nitrogen. For reconstitution of frozen cells we found that the use of dextran II0 inhibited leucoagglutination. The viability and function of the reconstituted leucocytes were assessed by their morphological appearance, their capacity to phagocytose and kill Candida albicans organisms, their ability to reduce the dye nitroblue tetrazolium (NBT) in vitro and to incorporate tritiated thymidine into DNA and by the growth of colony forming units (CFUc) in agar culture. With this method of cryopreservation the phagocytic function of mature neutrophils is retained to some extent but their capacity to reduce NBT and their microbicidal activity are completely lost. In contrast CFUc may remain after storage for periods of at least 2 years.


Remission maintenance therapy for meningeal leukaemia: intrathecal methotrexate and dexamethasone versus intrathecal craniospinal irradiation with a radiocolloid.

Thirty-two patients with meningeal leukaemia who achieved meningeal remission with intrathecal methotrexate (MTX) plus dexamethasone (DMT) were entered in a randomized study of two maintenance treatments: (a) I6 patients received intermittent intrathecal doses of MTX plus DMT, and (b) I6 patients received intermittent intrathecal doses of radioactive chromic phosphate (CROP). The population and clinical characteristics of the cases assigned to each maintenance regimen were similar. The duration of meningeal remission was 55-600 + d (median 550 d) for the MTX and DMT group and 56-555 d (median 360 d) for the CROP group. There was no statistical difference (P greater than 0.05) between the curves of the two groups. Intrathecal CROP seems to be as effective as intrathecal MTX plus DMT as maintenance treatment for intrathecal MTX plus DMT induced meningeal remission. Further uses of this compound should be explored but it seems to be dangerous to administer it by lumbar puncture.


Periosteal benign osteoblastoma of the mandible. Report of a case and review of the literature pertaining to benign osteoblastic neoplasms of the jaws.

A case of periosteal benign osteoblastoma arising in the mandible of a Caucasion male aged 9 years is presented. A review of the literature has produced 24 additional benign osteoblastic neoplasms of the jaws which have been delineated as osteoblastoma or osteoid osteoma. There seems to be a predilection for these lesions to occur in males and in the mandible. Osteoblastomata occur most frequently in patients under 20 years of age whereas osteoid osteomata arise mainly in persons over 25 years of age.


Presenile mandibular atrophy: its aetiology, clinical evaluation and treatment by jaw augmentation.

Presenile mandibular atrophy has been regarded as a bony condition in isolation. Direct vision of the mandible at the lower border and ascending rami at augmentation procedures in two cases clearly showed that the condition had affected the whole bone in all dimensions. A suggestion is made that mandibular atrophy arises as a result of many contributory factors, some local, but usually based on generalised undisclosed malabsorption states or osteoporosis.


Acute hepatic failure and Henoch-Schönlein syndrome appearing in a patient with severe cranio-facial  injuries.

A case of acute hepatic failure is described  following multiple general anaesthetics administered for the treatment of cranio-facial trauma. The dangers of multiple anaesthetics within a short period is stressed. The possibility that unexplained pyrexia following a general anaesthetic may be and early warning sign is mentioned in relation to this case. The subsequent development of the Henoch-Schönlein syndrome is reported, and the occurrence of the two conditions in the same patient is thought to be possibly unique.


Cyanoacrylate tissue adhesive in osseous repair.

Isobutyl 2-cyanoacrylate monomer placed in an osseous defect excited an intense acute inflammatory response in the early stages of repair. Fibrous encapsulation of the adhesive followed, and chronic inflammation supervened for as long as the cyanoacrylate remaine. Damage to established bone, presumable due to toxic breakdown products, occurred even at a distance from the adhesive. Osteoblastic activity was retarded where cyanoacrylate was in close proximity, recovering as fibrous encapsulation and macrophage activity provided protection. Extensive marrow damage was seen, recovery similarly following fibrous protection. Repair progressed as cyanoacrylate was removed. The findings of this investigation, together with other reports of unfavourable bone reaction to isobutyl 2-cyanoacrylate (Kerr & Smyth, 1971; Corn et al., 1972) suggest that it should not be used in bone surgery. An ideal adhesive for use in bone repair should promote rather than retard osteoblastic activity, and should resorb apace with bone regeneration. Thus isobutyl 2-cyanoacrylate does not fulfil the criteria for the ideal adhesive. Hopefully, future development of the cyanoacrylates will circumvent their current disadvantages, resulting in an adhesive acceptable for clinical use in osseous repair.


Human deoxythymidine kinase II: substrate specificity and kinetic behavior of the cytoplasmic and mitochondrial isozymes derived from blast cells of acute myelocytic leukemia.

Cytoplasmic and mitochondrial deoxythymidine kinase isozymes derived from the blast cells of acute myelocytic leukemia differ in their substrate specificity and kinetic behavior. These enzymes require divalent cations for their activity. The data suggest that the major role of idvalent cations is to chelate with ATP; the complex thus formed serves as the phosphate donor for the reaction. The activity of various triphosphate nucleosides as a phosphate donor for cytoplasmic deoxythymidine kinase is as follows: ATP = dATP greater than ara-ATP greater than GTP greater than CTP greater than dGTP = dCTP greater than dUTP, whereas for mitochondrial deoxythymidine kinase, the order of activity is ATP greater than CTP greater than UTP = dATP greater than ara-ATP greater than dGTP = dCTP greater than dUTP. Neither IdUTP nor dTTP could serve as a phosphate donor in the reaction catalyzed by either isozyme. From the many pyrimidine analogues tested for their binding affinity to each of these isozymes, I-dUrd and Br-dUrd had high good affinity which was equivalent to that of deoxythymidine. 5-Allyl-dUrd, 5-ethyl-dUrd, and 5-propyl-dUrd were only weakly bound to each isozyme. 5-I-dCyd, 5-Br-dCyd, dCyd, and 5-vinyl-dUrd were tightly bound to mitochondrial deoxythymidine kinase but not to the cytoplasmic isozyme. dTTP and I-dUTP are potent inhibitors of the reaction catalyzed by both isozymes. In contrast, dCTP and ara-CTP are potent inhibitors only of the mitochondrial isozyme, but not of the cytoplasmic isozyme. ATP-MG2+ acts as a sigmoidal substrate of the cytoplasmic isozyme with a"Km" of 0.22 mM, and as a regular substrate of the mitochondrial isozyme with a Km of 0.1 mM. Deoxythymidine acts as a regular substrate for both cytoplasmic and mitochondrial isozyme with a Km of 2.6 and 5.2 muM, respectively. Initial velocity as well as product inhibition studies suggest that the cytoplasmic isozyme catalyzes the reaction via a "sequential" mechanism. In contrast, mitochondrial deoxythymidine kinase catalyzes the reaction via a "ping-pong" mechanism.


Blood lymphocytes in acute lymphoid leukaemia in remission and in relapse. Predictive value of electrophoretic mobility and refringence.

Blood lymphocytes were studied during the evolution of acute lymphocytic leukaemia, including remissions and relapses, under chemotherapy and immunotherapy. Lymphoblasts migrate as a uniform population and have a mean electrophoretic mobility of 1.04 mum-sec-1. V-1cm. These lymphoblasts are also refringent. The relapse seems to be preceded by a slowing of the electrophoretic mobility of fast cells and a rise in the percentage of refringent lymphocytes.


Phase II trial of active immunotherapy of acute myeloid leukemia.

18 acute myeloid leukemia patients were submitted to a Phase II active immunotherapy trial. The median duration of complete remission (CRD) (60 weeks) and of survival after remission (SAR) (104 weeks) were longer than those for our historical control groups. However, the CRD and SAR curves were not broken to form a "cure expectancy" plateau, as was the case for acute lymphoid leukemia.


[Cerebrospinal fluid cytology in acute leukemias. (Use of cytocentrifugation for blast cell identification)].

The authors studied cerebrospinal fluid (CSF) in 51 patients with malignant blood diseases. 136 assays were performed over a three month period. In children, two technics were used; in the first case, smears were done with cells obtained through centrifugation; in the second case, CSF was directly thrown on glass slides in a special cytocentrifuge. Only the latter was performed for adults. In each case, the results of the cytological analysis were compared with those of cyto-chemical assay and clinical status.


[Possibility of detecting human embryonal leukemia antigen].

A possibility of detecting embryonic leukemic antigen on human leukemic blast cells in an acute human leukemia cytotoxicity test with the sera and 7S and 19S serum immunoglobulins of the placental blood was studied. The presence on the blast cells of patients suffering from acute leukemia of an antigen detectable by antibodies of placental blood (of parturients) was demonstrated; this antigen was absent on the leukocytes of healthy donors.


Human acute myelomonocytic leukemia: serologic studies with simian antisera.

Simian antisera to human leukemia cells were able to distinguish antigens specific for lymphocytic types of leukemia from those expressed on certain myeloid leukemia cells. In this investigation, cells from acute myelomonocytic leukemia patients (AMML) were examined for their membrane-associated leukemia antigens. Simian antisera to both lymphocytic and myelogenous leukemia cells lysed cells from AMML donors. Monkey antisera to AMML cells, by direct microcytotoxicity testing, were cytotoxic for cells from all AMML patients, as well as for cells of certain patients with myeloid leukemia. Cells from patients with lymphatic leukemia were nonreactive. However, absorption studies indicated an antigen present on cells from patients with chronic lymphocytic leukemia which cross-reacted with AMML cell antigens. Sequential analyses of the serologic reactivity of cells from AMML patients undergoing chemotherapy corresponded with the clinical course of the patient, even though there was little correlation between the percentage of blast cells present and the per cent cytotoxicity with the antisera. At certain times a higher percentage of seropositive cells could be detected over that seen on morphological evaluation. The estimation of leukemic cells by serologic means could aid in the diagnosis and management of AMML patients during chemotherapy.


Granulopoiesis in chronic myeloid leukemia. II. serial cloning of blood and bone marrow cells in agar culture.

Colony-forming cells (CFC) and CFC in S-phase were assayed in chronic myeloid leukemia (CML). A correlation was found between leukocyte counts and CFC of blood, suggesting that the leukocytosis of CML depended on expansion of the committed granulopoietic stem cell compartment. Serial studies performed in four cases demonstrated a decrease of the CFC in S-phase during early stages of developing leukocytosis, which was consistent with the operation of growth control mechanisms. During later stages, serial studies revealed that sudden increments of CFC S-phase coincided with rapidly growing leukocytosis, which was consistent with leukemic cell populations escaping growth control. H-thymidine labeling indices for differentiated precursor cells showed slight variations not coinciding with variations of the CFC S-phase fraction. Cyclic oscillations of the white cell count were observed in one case. The white cell count and the fraction of CFC in S-phase displayed a direct relationship, indicating that the occurence of cycles was not likely to be due to a negative feedback mechanism elaborated by mature granulocytes. In another case, marked cycling of the CFC S-phase fraction was found without distinct oscillations of the white cell count. The present work has emphasized the necessity for serial assays of parameters of cell kinetics in vitro in CML since changing relationships were found between stem cell and differentiated cell kinetics during different phases of the disease.