Detection of canine Batten disease with the EEG. Although it has been suggested that EEG changes appear early in the course of human Batten disease, these observations have been made only after the onset of clinical abnormalities and without immediate pathological correlation. In this brief report we have been able to document for the first time, abnormal EEGs in a strain of dogs proposed as a model for Batten disease. The degree of abnormality in the canine EEG correlated with the degree of clinical involvement and with the presence of pathological inclusions, resembling those seen in human Batten disease. In younger dogs, abnormal EEGs were obtained even before clinical manifestations of the disease. The large amplitude discharges reported with photic stimulation in children with the late infantile form of Batten disease were not elicited in the dog model. However, this dog strain is a model for the juvenile rather than the late infantile form although similarities between dogs and both forms of human Batten disease were seen. It is proposed that the EEG is both a method for early detection of this disease as well as a tool ot measure the degree of involvement. This information may be of use in relation to future therapeutic trials.


Latency of the steady state visual evoked potential. A technique has been devised to measure the latency of the steady state evoked potential (EP) to the separate flashes of a flickering light. The steady state method measures the averaged following EP to a flickering light. From the different averaged EP curves resulting from different averaged EP curves resulting from different intervals separating successive flashes, a latency is calculated which can be said to be the latency of a single response to a single flash of light. This latency is shorter for short inter-flash intervals (60-45 msec) than for the long inter-flash intervals (90-105 msec). The average short latency for three subjects was 61 msec and the average long latency 119 msec. These results agree reasonably well with other previous estimates of latency.


Focal positive spikes in electroencephalography. Focal positive spikes and sharp waves in clinical EEG are uncommon (about 1.3 per 1,000 EEGs in this series) and encountered chiefly in early life. All of out seven patients suffered from a convulsive disorder. These discharges must be differentiated from 14 and 6 c/sec positive bursts. Atifactual electrical transients with apparent focal positivity must always be ruled out. Whenever focal positive spikes and sharp waves are identified, it is advisable to search for simultaneous focal negative discharges. The literature indicates that focal positive spikes and sharp waves could be classified according to the presumed pathophysiological mechanisms and illustrative patients were described.


Indirect estimation of spinal cord conduction velocity in man. A method is described for deriving an indirect estimate of the velocity of impulse propagation in the spinal cord of intact man. The estimate is computed from measurements of motor and sensory nerve conduction velocity in the limbs, F-wave latencies, and the latencies of somatosensory evoked potentials. The mean estimated spinal cord conduction velocicy in normal subjects was found to be 55.1 m/sec, with a standard deviation of 9.9. This method appears to have potential application in the electrophysiological evaluation of patients with myelopathic disorders.


Amine repletion in the reserpinized cat: effect upon PGO waves and REM sleep. Selective repletion of 5-HT and catecholamines in the reserpinized cat was used to study the role of these biogenic amines in the regulation of PGO wave activity and sleep. The results include: 1. Repletion of 5-HT, following injections of D, L and L-5-HTP, suppressed PGORes in the pons and visual system. A consistent relationship between drug dose and duration of suppression was established. D-5-HTP failed to influence PGORes. L and D, L-5-HTP also induced a state closely resembling slow wave sleep and this change corresponded, temporally, with the period of wave suppression. 2. Repletion of catecholamined, following injections of L-DOPA, often caused behavioral arousal and a conversion from PGORes to PGOW. The molar dose of L-DOPA required to block PGORes was 10-20 times greater than that of L-5-HTP required for a comparable effect. In some cases, L-DOPA failed to arouse the cat, and in each of these instances, it failed to suppress PGORes. 3. L-DOPA consistently failed to induce a premature return of REM sleep in the reserpinized animal. These results suggest that 2 neuronal systems, one employing 5-HT and the other catecholamines, play a part in the regulation of PGORes, and presumably, PGOrem. The 5-HT system may be primarily responsible for suppressing PGOrem during slow wave sleep, with the catecholamine system playing a comparable part during wakefulness. Earlier reports that L-DOPA induces REM sleep in the reserpinized animal were not confirmed, indicating that the postulated role of catecholamines in the induction of this state should be reevaluated.


The definition of waking stages on the basis of continuous polygraphic recordings in normal subjects. Polygraphic examinations were made during the day on 6 normal subjects. Simultaneous evaluation of EEG, EOG and EMG was carried out over 30 sec epochs. The data thus obtained were correlated with the various types of behaviour and activities during the day and then interpreted. Six conditions could be defined corresponding to different waking stages. The analysis of the material obtained shows that the existence of these waking stages is of interindividual validity.


The scalp topography of human somatosensory and auditory evoked potentials. The waveform and topography of components of the scalp recorded somatosensory evoked poal (AEP) to click stimulation of the right ear, were determined for scalp electrode locations of the 10-20 system and for locations at the eye, mastoids, and posterior neck. Twenty-one SEP and twenty-two AEP components were analyzed. Differentiation of neurogenic and myogenic components was attempted on the basis of localization and variability. Some components of extracranial origin, apparently originating in frontal musculature, were small in most experienced subjects and large in most experimentally naive subjects. These and other presumptive myogenic potentials can distort adjacent neurogenic components. These data should aid in predicting SEP and AEP characteristics and in assessing myogenic distortion of neurogenic components.


Inter- and intrahemispheric differences in the peak frequency of rhythmic activity within the alpha band. EEG was recorded simultaneously from several scalp regions in 5 normal subjects and analysed, using a PDP 11/45 computer by means of an autoregressive model. Significant intra- and interhemispheric differences in the peak frequencies within the alpha band were observed, up to 0.8 c/sec. Local modality -dependent increases in the peak frequency were also observed, which were predominant in occipital areas during visual stimulation and in central regions during acoustic stimulation. In most cases an increase in the peak frequency occurred together with a marked decrease in power, which could be interpreted as a desynchronization of slow components within the alpha band. These peak frequency differences found in the scalp EEG lead to the assumption that there might also be different alpha rhythms at the level of the cortex.


Adaptive segmentation of EEG records: a new approach to automatic EEG analysis. The first step in a procedure for automatic EEG analysis is to compress the incoming data into a manageable format while preserving the essential diagnostic information. In our approach we mimic the visual procedure of looking through the record for segments and events of particular interest. We assume that the EEG is composed of roughly stationary segments of variable length, possibly superposed by sharp transients. By using an autoregressive model we have developed a procedure to detect the segment boundaries and locate transients, and to represent the information in the segments in terms of a set of parameters specifying their power spectra. In this way, the time structure as well as the frequency content of the signal is preserved. Examples of segmentation and transient detection are shown for several EEG signals, and the quality of the representation is demonstrated by simulating the original signal from the parameters. Possible applications to practical EEG analysis are discussed.


Focal reflex epilepsy with myoclonus; electrophysiological investigation and therapeutic implications. A middle-aged man suffering from myoclonic jerks of the right arm and leg and occasional grand mal seizures was investigated electrophysiologically. The EEG showed a left central spike focus which could be activated by any stimulus which distorted the biceps, triceps or brachioradialis muscles but skin stimulation was ineffective. Electrical nerve stimulation subthreshold to the alpha motoneurone fibres evoked cortical spikes and myoclonic jerks. The evidence supports the hypothesis that the myoclonus was triggered by muscle spindle afferent fibres (Ia) which projected to an epileptogenic focus in the sensori-motor area. A marked improvement of symptoms was achieved by a combination of baclophen and dipropylacetate.


Critical evaluation of the diagnostic value of systolic time intervals in the diagnosis of functional thyroid diseases. Comparison of results in a highly selected and a non-selected group of patients in relation to the blood PBI and T4I levels. The value of measuring systolic time intervals for the diagnosis of functional thyroid disorders was studied. We were able to confirm that the systolic time intervals, namely the preejection period (PEP) are significantly shortened in hyperthyroidism and protracted in hypothyroidism. We were able to prove the rectilinear correlation between the PEP interval and Ig PBI in both highly selected and unselected groups of untreated patients with thyroid disorders. We were able to show much lower diagnostic value of other systolic intervals (as Q-S2) and indices (Weissler's index) compared to PEP. We are able to enumerate some pathological cardiovascular states, where the PEP interval is considerably influenced. With due respect to above-mentioned problems, we are convinced that the PEP measurement is of real diagnostic value in the bed-side diagnosis of thyroid disorders, moreover we believe it might help to solve some theoretical problems.


Sex hormone-dependent brain maturation and sexual behaviour in rats. In male and female rats the endogenous steroid and gonadotrophin secretion was inhibited by injecting high doses of chlormadinone acetate (CmAc) from day 14 to 24 of life, i. e. during the period of brain maturation. In adulthood the males treated prepubertally with CmAc exhibited reduced sexual activity and fertility, whereas the females did not differ from the controls. More complete sex hormone deficiency during brain maturation was achieved by castration on day 14 of life. Controls were castrated at normal puberty time (40--60 days). Both groups were then substituted with androgens or oestrogens. In the females castrated on day 14 no impairment of sexual behaviour was observed as compared to the later castrated controls. In contrast, the early castrated males showed delayed onset of mounting behaviour. At autopsy, the weights of their sex organs were found to be lower than in the controls despite equal testosterone replacement for several months. These findings speak in favour of a permanently diminished responsiveness to androgens in males having been exposed to more or less severe androgen deficiency during sex specific brain maturation. Hence, the maturation of a male hypothalamus as well as the differentiation appears to depend at least in part on the presence of androgens, whereas in females it runs without hormonal influence.


Purification and characterization of microsomal and lysosomal beta-glucuronidase from rat liver by use of immunoaffinity chromatography. Rat liver beta-glucuronidase (EC 3.2.1.31), both from microsomal and lysosomal fractions, were purified about 9500-fold over the homogenate with high yield using affinity chromatography prepared by coupling purified specific immunoglobulin G against rat preputial gland beta-glucuronidase to Sepharose 2B and isoelectric focusing. The purified enzymes appeared homogeneous on electrophoresis in polyacrylamide gel and had a molecular weight of approximately 310000. In dodecylsulfate polyacrylamide gel electrophoresis, the microsomal beta-glucuronidase showed a single band corresponding to a molecular weight of 79000, while the lysosomal beta-glucuronidase had three distinct bands which consisted of one major and two minor bands corresponding to molecular weight of 79000, 74000, and 70000, respectively. A broad pH activity curve with a single optimum at pH 4.4 was observed in both the microsomal and the lysosomal beta-glucuronidases. Immunological gel diffusion technique with rabbit antiserum against rat liver lysosomal beta-glucuronidase revealed that both enzymes had the same or quite similar antigenic determinants.


The virtual absence of antigenic cross-reactivity between functionally distinct trout hemoglobins. The antigenic properties of the hemoglobins of two species of rainbow trout, Salmo irideus and Salmo gairdneri, have been compared. Each of these species possess two different classes of hemoglobins, the members of the first of which have no Bohr effect while those of the second exhibit a pronounced pH dependence of their ligand affinities. The hemoglobins from these two species are antigenically indistinguishable. However, between the two classes of hemoglobins there is almost no immunological cross-reactivity.


Terminal riboadenylate transferase from Escherichia coli. Characterization and application. Catalytic properties of terminal riboadenylate transferase from Escherichia coli and the products of the enzymic reaction were investigated. The kinetic analysis revealed that the reaction obeys the sequential ordered bi-bi mechanism. The application of conditions elaborated in this study resulted in the synthesis of products of defined size and efficient primer utilization. The tRNA(rA)n obtained was a good template for the synthesis of complementary DNA with reverse transcriptase.


Proton translocation and ATP formation coupled to electron transport from H2O to the primary acceptor of photosystem 2. 1. The rate of electron transport from H2O to silicomolybdate in the presence of 3-(3-4-dichlorophenyl)-1,1-dimethylurea (diuron) (which involves the oxygen-evolving enzyme, the photochemistry of photosystem 2 and the primary electron acceptor of photosystem 2) is controlled by internal pH. This is based on the shift of the pH profile of the rate of electron transport upon addition of uncouplers, or by using EDTA-treated chloroplasts. Both stimulation and inhibition of electron transport by addition of uncouplers (depending on external pH) could be observed. These effects are obtained in the diuron-insensitive photoreductions of either silicomolybdate or ferricyanide. These experiments provide strong evidence that a proton translocating site exists in the sequence of the electron transport H2O leads to Q (the primary acceptor of photosystem 2). 2. The photoreduction of silicomolybdate in the presence of diuron causes the formation of delta pH. The value of delta pH depends on the external pH and its maximal value was shown to be 2.4. The calculated internal pH at different external pH values was found to be rather constant, namely between 5.1 -- 5.2. 3. Electron transport from H2O to silicomolybdate (in the presence of diuron) does not support ATP formation. It is suggested that this is due to the fact that the delta pH formed is below the "threshold" delta pH required for the synthesis of ATP. By adding an additional source of energy in the form of a dark diffusion potential created in the presence of K+ and valinomycin, significant amounts of ATP are formed in this system.


An undeservedly neglected prostatectomy: Fabre's technique. Fabre's prostatectomy technique was applied to 100 consecutive unselected patients with no mortality and minor complications. Three technical failures were recorded. No urethral catheter was used, the bladder being drained through a lateral hypogastric stabwound. The incidence of urinary infection was greatly reduced in this series.


Estimation of the size of prostatic adenoma by ultrasonography. A preliminary report. 17 patients with prostatic adenoma awaiting surgery were examined. The size of the adenomas was established by palpation, cystoscopy, urethro-cystography and ultrasonography. Echographic scanning was found to yield the most accurate results.


Prostatic desiccation used in poor-risk patients with benign and malignant prostatic obstruction. A small percentage of patients with infra-vesical obstruction cannot tolerate open or transurethral prostatectomy. In these cases cryoprostatectomy is a possibility, we have, however, used another method based on heat destruction of the tissue. The results in 24 poor-risk patients were satisfactory, without any serious postoperative complications, and with excellent long-term results in 80% of the cases. The only complication is a high rate of incontinence. Until this problem has been solved the procedure should be reserved for poor-risk patients.


Identification of cells or origin of non-primary afferents to the dorsal column nuclei of the cat. In order to identify cells of origin in the spinal cord of non-primary afferents to the dorsal column nuclei (DCN), the retrograde transport of horseradish peroxidase (HRP) has been utilized in adult cats. 10 to 30% HRP was injected bilaterally (0.6 mul per side) in the dorsal medulla of nine cats. In most instances the spread of the injected enzyme extended a few millimeters rostrocaudally and infiltrated the DCN as well as other nuclei and fiber tracts. Labelled cells in these cases are numerous in the upper cervical, brachial and lumbosacral cord but are sparse in thoracic segments below T1. At upper cervical levels (C1-C4) HRP-positive neurons are distributed throughout the grey matter but are especially concentrated in the medial part of lamina VI. Cells projecting to the dorsal medulla are mainly localized in lamina IV and, more ventrally, along the medial border of the dorsal horn in the brachial and lumbosacral cord. Labelled cells at these levels are also scattered within lamina I and laminae VI through VII in cases in which the focus of the injection involved extensive portions of the medulla. From cases in which bilateral HRP injections were preceded by spinal tractotomy, it appears that the axons of at least the majority of labelled cells in lamina IV ascend in the ipsilateral dorsal quadrant of the spinal cord. In another group of adult cats, 0.1 to 0.25 mul of 30 to 50% HRP was injected unilaterally in the dorsal medulla at the level of, or rostral to, the obex. With these volumes of exogenous enzyme, an intense reaction product is largely confined within the limits of the DCN. Labelled cells in these cases are found almost exclusively in the medial part of lamina VI at upper cervical levels and, at brachial and lumbosacral levels, throughout lamina IV and medially in lamina V on the side of the cord ipsilateral to the injection. The results are discussed in relation to the organization of the dorsal horn ascending pathways with special reference to cells or origin of the spinocervical tract.


Significance of the maillet method (ZIO) for cytochemical studies of subcellular structures. The present knowledge on the methodology, specificity, localization, cytochemical significance and experimental variations of the zinc iodide-osmium tetroxide (ZIO) staining are reviewed. Some new findings supporting the concept that ZIO reacts with -SH groups in some structures under specific conditions are also communicated. In this respect the effect of in vitro pretreatment with -SH reagents on ZIO staining, already described in different kinds of synaptic vesicles, was studied in rod photoreceptor outer segments. It was observed that the intra- and extradiskal electron opaque deposits, present in untreated rod outer segments directly stained with ZIO at 4 degrees C for 2 h, were enhanced by previous incubation with dithioerythrytol (DTE), which protects -SH groups and reduce -S-S-bridges; when N-ethyl-maleimide (NEM), a -SH blocking agent was used directly or after DTE, the electron opaque deposits were considerably reduced or abolished. Furthermore the influence of previous incubation with cysteine on ZIO staining was studied in the rat pineal gland. In the controls ZIO made at 4 degrees C for 2 h, reacts strongly with the matrix of the small granulated synaptic vesicles in the pineal nerves; no electron opaque deposits are seen in the membranes of the vacuolar system. Previous incubation with cysteine 5 mM in phosphate buffer makes negative ZIO reaction in the matrix of the synaptic vesicles while with a concentration of 50 mM cysteine, a partial recovery is observed. In both concentrations the membranes of the vacuolar system appeared covered by patchy electron opaque deposits.


Amino acid and protein concentrations of human follicular fluid. The amino acid and protein composition of human follicular fluid, obtained during surgery from women with polycystic ovaries, and of a simultaneously obtained sample of blood plasma were studied. In general, amino acid concentrations were higher in follicular fluid than in blood plasma: only the concentration of Cys was significantly lower in follicular fluid than in plasma, while Asp, Thr, Glu, Glu-NH2, Gly, Ala, and Met showed concentrations that were not significantly different in either biologic fluid. The concentration of basic amino acids, taken as group, was almost twice as high in follicular fluid as in plasma. The total protein concentration in follicular fluid was not significantly different from that in blood plasma. However, the follicular fluid albumin concentration was higher and globulin concentration lower than the respective concentrations in plasma. Polyacrylamide gel disc electrophoresis of follicular fluid showed some consistent differences, particularly in the alpha-globulin region, with the pattern observed in blood plasma. These findings are discussed in relation to the possible role of follicular fluid in capacitation and egg segmentation.


[Effects of verapamil on sinusal function and on atrioventricular conduction along normal and abnormal pathways, in patients with pre-existing troubles of excitation conduction (author's transl)]. Effects of verapamil (5 mg i.v.) on excitation conduction in 20 patients who already had a basic alteration (7 with ventricular pre-excitation syndrome) were studied by His electrogram, during spontaneous sinusal rhythm and atrial electrostimulation in increasing frequencies. In 4 cases, a test crossed with atropine was carried out. The effects of the drug on the effective refractory period of the A-V node and the anomalous tract in 3 patients with W.P.W. syndrome of Kent's bundle were studied. The effects were: no significant modifications in the sinusal frequency; increase in the corrected preautomatic pause only in cases with sick sinus node syndrome and serious basic compromise of the sinus node function; slowing down of A-V conduction in the supra-hisian area and increase of the effective refractory period of the A-V node; no modification of the intra-atrial conduction, or the under-hisian and intraventricular A-V conduction; uneven slowing down of conduction along the anomalous tract of the pre-excitation syndrome of the James bundle; modification of the effective refractory period of the anomalous tract of the Kent bundle type, variable from case to case. On the basis of the electrophysiological properties, the possibilities and limits of use of the drug in sick sinud node syndrome in the common supraventricular paroxymal tachycardias, in atrial fibrillation, atrial flutter and arrhythmias of the ventricular pre-excitation syndrome are emphasized.


[Adverse effects of drugs: syncope due to prenylamine (author's transl)]. The authors report on 4 Intensive Care Unit cases, hospitalized for syncopes due to serious ventricular arrhythmias. They all presented long Q-T and were receiving treatment with prenylamine. Improvements were observed on suspension of the drug, suggesting therefore that during this treatment, frequent electrocardiographic checks, especially for elderly patients, should be carried out. Caution should also be exercised in associations with other chinidinosimiles and hypokaliemic drugs


[Blood bunaphthine during dynamic physical exercise and anti-arrhythmic action]. The course of bunaphtinemia during submaximal exercise was studied. To 5 patients showing the appearance or the increase of extrasystole, both ventricular and supraventricular, during ergometric test on the bicycle ergometer, bunaphtine was administered by the following method: a first dose of 0.5 mg/kg was injected endovenously in 2 minutes followed by a constant endovenous infusion at the speed of 2.5 mg/min, throughout the exercise. Doses were calculated referring to a pharmacocynetic pattern with two compartments and supposing an apparent distribution volume of 3 l/k. Resulting bunaphtinemia curves showed a steady state and were completely above the minimum effective standard throughout the test. In all patients the drug prevented ventricular arrhythmias and compared to the standard reduced the supraventricular arrhythmias by 80%.


Serum alpha-fetoprotein in patients with massive hepatic necrosis. Serum concentrations of alpha-fetoprotein (AFP) were measured by radioimmunoassay in 12 patients with massive hepatic necrosis, 11 of whom died. Levels were significantly elevated after the 8th day of illness in 8 of the 9 patients who died between the 10th and 60th day, and in the 1 patient who survived. All 9 patients with increased levels of serum AFP exhibited histological evidence of hepatic regeneration. These findings indicate that the rise in serum AFP in massive hepatic necrosis is related to the duration of survival after the onset of illness, but does not necessarily imply ultimate recovery. Because available evidence suggests that the serum AFP level reflects hepatic regenerative activity, it appears that the onset of regeneration in fulminant hepatitis is delayed until the 2nd week of illness.


Cellular subclasses in human leukemic hemopoiesis. Cellular organization and communication in leukemic hemopoiesis may be compared with its counterpart in normal hemopoiesis. Results obtained using cell culture methods have provided some support for the view that leukemic hemopoiesis, like normla hemopoiesis, may involve 3 levels of differentiation: leukemic stem cells, committed leukemic progenitors, and more mature cells. Evidence is also beginning to emerge that leukemic populations may be regulated by messages from the environment in a manner analogous to normal hemopoiesis. The apparent similarities between leukemic and normal hemopoiesis raise, the possibility that the target cell for leukemic transformation is the normal pluripotent stem cell. The development of culture methods for the production of leukovirus-like particles from human leukemic cells provides a possible first step toward the direct identification of leukemic target cells.


[Results of palliative operations in infants with pseudotruncus arteriosus (author's transl)]. A palliative procedure in patients with pulmonary atresia with VSD should improve arterial oxygen saturation, allow growth and development, and promotes a uniform dilatation of the pulmonary arteries. Thirty-three severely symptomatic patients, ranging from 5 days to 24 mths of age and from 2,4 to 11 kg of weight underwent a variety of palliative operations, including the ascending aorta-right pulmonary artery shunt (intrapericardial: 15 cases; extrapericardial: 14 cases), the Blalock shunt (4 cases). In two cases, both with absence of the left pulmonary artery, a Waterston shunt was performed using cardiopulmonary by-pass. The operative mortality was 20%. In two patients an additional shunt procedure was deemed necessary due to persistent cyanosis. All the survivors improved in terms of arterial oxygen saturation, growth and development. There were no late deaths (mean follow-up: 23 months).


Bovine leukemia virus: an exogenous RNA oncogenic virus? Short term cultures of bovine leukemic lymphocytes release virus particles with biochemical properties of RNA oncogenic viruses. These particles, tentatively called Bovine Leukemia Virus (BLV) have a high molecular weight-reverse transcriptase complex and a density averaging 1.155 g/ml in sucrose solutions. Molecular hybridizations between BLV-3H cDNA and several viral RNAs show that BLV is not related to Mason-Pfizer Monkey Virus (MPMV) Simian Sarcoma Associated Virus (SSV-1) Feline Leukemia Virus (FeLV) or Avian Myeloblastosis Virus (AMV). Rauscher Leukemia Virus (RLV) exhibits a slight but reproducible relatednesse to BLV. The high preference of BLV reverse transcriptase for Mg++ as the divalent cation suggests that BLV might be an atypical mammalian leukemogenic type C virus. Hybridization studies using BLV 3H cDNA as a probe suggest that the DNA of bovine leukemic cells contains viral sequences that cannot be detected in normal bovine DNA.


B- and T-cell determination in ALL.

B- and T-cell determination in ALL. The influence of different cytostatic treatment schemes on T- and B-cell behaviour has been studied in children with ALL and UAL. Under these treatment schemes the percentage of B-cells decreased, while the percentage of T-cells remained within normal limits. In long-term remissions, we found normal values. In the first attack of ALL before therapy, a different behaviour of lymphoid cells was found. One group of patients had no lymphoid cells with membrane-bound Ig and no rosette forming cells; a second group had mainly T-cells, and a third group showed normal values of lymphoid cells with membrane-bound Ig, but the ability of rosette formation was slightly diminished. Whether this membrane-bound Ig is really cell-produced or only attached to the cell-membrane (blocking antibodies?) is discussed. Capping and pitching behaviour was observed. There were no differences in cell-membrane fluidity as compared with the normal controls.


The amoebocytic corpuscles in the circulating fluid of the lamelli-branches, Indonaia caerulia and Parreysia (Parreysia) favidens. The circulating amoebocytes of the freshwater mussels, Indonaia caerulia and Parreysia favidens have been studied. The total number of amoebocytes is low and variable, and the individual to individual variation in total counts is particularly significant. The amoebocytes are of 3 main types: Acidophils, Large Basophils and Small Basophils. Acidophils contain large acidophilic granules and basophils fine basophilic granules within the cytoplasm. Acidophils are the largest and small basophils the smallest. The greater volume of the cell is occupied by cytoplasm in acidophils and large basophils and by the nucleus in small basophils. Large basophils are the most and small basophils the least abundant. Amoebocytes clump together by means of filipodia. Large basophils possess these protoplasmic processes in the greatest abundance, and partake most actively and in largest numbers in clumping; while small basophils lack filipodia and play an absolutely passive role. Clumping progressively becomes more extensive with passage of time following cardiac injury inflicted during blood collection. I. caerulia appears to be generally more efficient than P. favidens with regard to clumping reaction. The different structural, numerical and behavioural aspects of the amoebocytes have been considered with reference to their probable causative factors and functional import.


Blood of the common indian weaver birds Ploceus philippinus and Ploceus benghalensis (Linnaeus). The blood contents of two common Indian weaver birds, Ploceus philippinus and Ploceus benghalensis have been studied. Morphology of RBC and WBC, total differential count, the number of RBC and WBC, Hb contents, PCV, MCV, MCH, MCHC, ESR, haemin crystal structures, coagulation and prothrombin time, glucose and cholesterol contents were calculated and compared with the haematological data recorded for other birds and vertebrates. Variation with respect to length and breadth of the erythrocytes and length of the nucleus of the RBC were also discussed. Males have higher RBC number and Hb content in these birds. The mean RBC number and Hb content were also more than in fishes, amphibians and reptiles but little less than in man. The RBC number for males of both the species do not differ significantly but the Hb contents in males and females of P. benghalensis differ significantly but this was not found in P. philippinus. Again the Hb content in male of both the species differ significantly but this was not true in females. Like Passer and Columba large number of polymorphs and lymphocytes were present but only a few basophils was observed in most of the slide preparations. No special type of haemin crystals were observed in any sex of both the species. The coagulation time was more than Passer and Columba but less than in man. There was also no marked difference in both the species with respect to prothrombin time. In both the species blood glucose was more in female than male but there was no marked difference in both the species.


[Problems in the treatment of stem cell leukemias in aged patients]. Stem-cell leukemias will reveal a second peak of frequency at old age. The cytochemical differentiation in 26 patients of old age revealed a preponderance of myeloblastic forms. Moreover, a slight accumulation of monocytic and myelo-monocytic types could also be observed. In spite of this apparently unfavourable cytochemical differentiation the relatively good capability of myeloblastic leukemias of responding to cytostatic treatment was surprising. However, no cytostatic maximum programmes should be chosen in view of the low regenerating ability of the bone marrow in old patients.


[Loss of blood and carbon tetrachloride poisoning]. In rats the induced enhancement of glutamic-pyruvic transaminase and leucine aminopeptidase activity in plasma to 5.2 mMol CC14/kg (per 05) is potentiated after repeated drawing of blood. The DL50 of CC14 following oral application in rats after loss of blood is reduced significant comparatively to controls and to animals with increased content of haemoglobin in blood.


Susceptibility of volume stress in Colisa fasciatus. Intraperitoneal injections of 0.6% NaC1, commonly used as injection vehicle, at 10 mul/g, but not at 5 mul/g. elicit significant (p less than .05) transitory erythropenia, leucopenia, and thrombopenia at selected post-injection time intervals in female Colisa fasciatus, a fresh water teleost. It is suggested that administration of large volumes of injection fluid per gram body weight of experimental animals should be avoided lest it might distort physiological parameters, particularly those relating to blood components, under study.


[Intravital survival and deformability of weakly amidinated rat erythrocytes]. Rat erythrocytes previously labelled with 51Cr were treated with 0.1 mM and 0.5 mM dimethyladipic imidate (ADE) pH 9.5, respectively, or with borate buffer pH 9.5 for 15 minutes each. After reinjection into rats of amidinated or nonamidinated erythrocytes their elimination form the streaming blood was followed for 50 days (0.1 mM ADE) or 38 days (0.5 mM ADE). During the 1st day about 10% of amidinated erythrocytes were sequestered. There was no increased initial elimination rate of borate incubated red blood cells detectable. During the following period the elimination rate of erythrocytes amidinated with 0.5 mM ADE was slightly greater than in the case of erythrocytes treated with 0.1 mM ADE. The mean life span of 0.5 mM ADE-erythrocytes was shorter compared with the controls and with 0.1 mM ADE-erythrocytes. Red blood cells previously treated with 0.5 mM ADE are significantly less deformable. Presumably, the stiffness of amidinated erythrocytes causes their increased elimination rate.


[Mechanical resistance of amidinated human erythrocytes]. The amidination reactions by means of dimethyl adipimidate (0.25-10.0 mM) or dimethyldodecane-imidate (0.1-1.0 mM) cause an alteration of the mechanical resistance of red blood cells. Low amidination results in peripheral cross-links of erythrocytes whose mechanical resistance increase relative to borate buffer treated cells. Increasing cross-linking reduces the mechanical resistance of erythrocytes, which finally appears to have become restored. The final state, however, is characterized by an almost complete cross-linking of the cell, which than no longer behaves like an osmometer.


[The effect of splenectomy, produced chemically by means of ethylpalmitate, on the formation of heteroagglutinins in the rat]. The formation of heteroagglutinins against human O-erythrocytes was pursued in Wistar rats splenectomized "chemically" by means of intravenous injections of ethyl palmitite. Contrary to some data in literature the initial inhibition in the formation of antibodies was replaced by a significant titre increase ranging from the 8th to the 14th day following immunization. The tween 20 contained in the emulsion of ethyl palmitic did not influence the formation of heteroagglutinins. The examinations show that a possible use of palmitic ethyl for immunosuppression is questionable.


Filtrability of erythrocytes in "hypersplenic" rats. The values of haemoglobin, reticulocytes and half-times of the filtrability of non-washed and washed erythrocytes were examined in male albino rats, Wistar strain, after i.p. injections of methylcellulose (MC) and compared with controls. In individual experiments the rats received 2 to 32 injections of MC. In injected animals, the filtrability of non-washed erythrocytes was altered. The filtrability half-times of the washed erythrocytes did not differ from the controls. Thus, the filtrability is altered for extracorpuscular reasons. "Hypersplenism" being completely developed, (after 32 MC injections), the filtrability of non-washed erythrocytes repaired when the application of MC had been discontinued, the reticulocyte values remained however increased. Problems of the mechanism of anaemia in experimental "hypersplenism" after MC injections in rats and relations between the altered filtrability of the erythrocytes and the haemolysis are discussed.


[The effect of inosine, inorganic phosphates and pyruvate on erythrocyte glycolysis metabolites under conditions of preservation]. Human erythrocytes were stored as resuspensions in solutions containing citrate (Z), inosine + citrate (I), inosine + phosphate (IP), and inosine + phosphate + pyruvate (IPP). The storage was made at + 4 degrees C for 6 weeks; the initial pH-value amounted to 7.4 at + 4 degrees C. The cellular concentrations of 2.3 DPG, ATP, G6P, FDP and DOAP + GAP were determined. The following results were obtained: 1. During the storage in stored Z-blood the 2.3 DPG concentration will fall below 10% of its initial value; it will remain nearly unchanged in stored I-blood and will increase to 170% in stored IP-blood, to 270% of its initial value in stored IPP-blood. 2. The ATP concentration of cells will fall to about 50% of its initial value at the beginning of the storage of all stored blood. After that it will only increase to about 80% of its initial value in stored IP- and IPP-blood. 3. During the storage the G6P concentration will increase to the highest degree in stored IPP-blood and if high pyruvate concentrations are not present, it will have a reciprocal behaviour towards the FDP and triosephosphate level. The results were discussed in view of the regulation of glycolysis under storage conditions.


[Fibrinolytic properties of a heparin-ocrase complex]. The obtained heparin-ocrase complex includes properties of inhibiting coagulation and a high fibrinolytic activity in vitro and in vivo. The fibrinolytic activity of the heparin-ocrase complex is higher than the equivalent amount of ocrase. The fibrinolytic activity of the complex is not only evident on non-stabilized fibrin plates, but likewise on stabilized ones and at the presence of inhibitors of enzymatic fibrinolysis, such as Trasylol and epsilon-aminocaproic acid. The complex formation between heparin and protease was confirmed by means of cross-paper electrophoresis and spectrophotometry.


[Micromethod for the determination of heat fibrinogen]. Description of a micromethod for determining heat fibrinogen where 0.06 to 0.08 ml of citrate plasma are only required. The results are similar to those of the heat fibrinogen method according to SCHULZ, yet they are by 15% below the average values of the Biuret test. The method is particularly suited as a quick orientating determination of fibrinogen for paediatrics and neonatology. A time of 30 minutes approximately is required for it.


[Studies on cryoprecipitates. 6. Osmolality and electrolyte conductivity]. By measuring the osmolality of plasma and the cryoprecipitate gained by it as well as by measurements of conductivity the previously reported observations about the enrichment of electrolytes in cryoprecipitates could be confirmed. The findings show that these preparations represent hyperosmolic solutions. This fact should by kept in mind when applying them.


[Review: Ontogeny of the oxygen transport in the blood]. The biological importance of the oxygen affinity of the tetrameric haemoglobin molecule and its dependency from co-factors is described. Oxygen affinity variations during development from embryonic to adult values are discussed in respect to oxygen uptake from maternal blood via placenta, in lungs and gills as well as to oxygen delivery into tissues. Comparative aspects of the molecular mechanisms leading to affinity changes are presented.


T cells, B cells and intermediate forms in the newborn studied by scanning electron microscopy and phosphatase marker. Scanning electron microscopic studies of peripheral blood lymphocytes showed that percentage of T cells was lower in four cases of premature infants born between 30th and 34th week of gestation when compared with that in four cases of term infants (18.6% and 39.9% counted from 956 and 1,379 lymphocytes, respectively). The occurence of lymphocytes with intermediate patterns of surface morphology (I cells) was noted in both groups studied. Percentages of B and I cells were higher in the premature than in the term infant (26.3% and 55.1% and 20.0% and 39.1%, respectively). Analogous tendency in the T cell occurence in the premature and the term infant was demonstrated with acid phosphatase as T cell marker.


Formation of multinucleated giant cells from circulating blood cells cultivated in diffusion chambers. Autologous circulating rabbit blood cells have been cultivated in Millipore diffusion chambers implanted intraperitoneally for 13 days. During this period multinucleated giant cells were formed within the diffusion chambers, confirming a hematogenous origin of these cells. The diffusion chamber technique might be helpful for the investigations of factors initiating the formation of multinucleated giant cells.


[Changes in the cellular immune reaction in the course of acute lymphatic leukemia]. In a seven years course study the parameters of cellular immunoreaction were elaborated in more than 100 children by means of the lymphocyte transformation test and the macrophage migration inhibition test. The transformation response revealed a dependence on the stage, course of the disease and regime of therapy during the tests with unspecific, specific and tumorspecific antigens. Compared with all antigens the transformation in the first crisis and in the recidives is significantly lower than in the remission. In spite of continuous immunosuppressive therapy in a cytostatic treatment lasting for years, the increase of the transformation rates is concealed by the fact that a positive selection of children with favourable courses can be evaluated in single test groups with advancing time of illness. The results for the prognosis of the disease and the transformation rates depending on the age of disease and the cell type are identical. The result of reaction with leukaemic cells as antigens enables prognostic conclusions to be made during the time of remission. Tests with leukaemic cells in myeloic leukaemias reveal a marked dependence on stages. In lymphatic forms a proceeding influence of the responding capacity of the T-lymphocyte population must be assumed. The difference in the results of reaction in cells from different stages must be discussed in connection with a possible change of antigens.


[Repeated, 2-10 fold asparaginase treatments in children with lymphoproliferative diseases]. In 42 children being in the advanced stage of an acute lymphoblastic leukaemia as well in 7 children with lymphosarcoma a total of 83 series of treatment with L-asparaginase were carried out. During the first blastic crisis of acute leukaemia 74% of complete or partial remissions could be obtained by two treatments and 52% by the following ones. The best results were obtained by organ manifestations of acute leukaemia (80% of complete or partial remissions). Less satisfactory results were achieved in treating lymphosarcoma. All remissions were only of a short duration.


[Results of polychemotherapy and immunotherapy in acute leukemias]. For the purpose of evaluating the efficiency of an unspecific immunostimulation in acute leukaemias the results of treatment obtained from two groups of patients (a total of 55 children) were compiled. In the first group an unspecific immunostimulation with vaccination (BCG, diphtheria-tetanus-pertussis, measles) could be observed after the induction of remission during a cytostatic maintenance therapy. In the second group a polychemical therapy and the CNS-irradiation was applied according to the treatment scheme developed by the working team of Donald Pinkel. The group of patients treated with unspecific immunostimulation involved a high percentage of surviving children. In total there was no essential difference between the treatment results of both schemes of therapy during our period of observation. As before, the treatment of hyperleukocytic forms of leukaemias will cause particular difficulties.


[Possibilities for the treatment of varicella-herpes zoster infections in juvenile leukemia]. Chicken pox and herpes zoster represent afraid complications in patients with malignant diseases which may take a noxious course. During the sequence of two chicken pox epidemias in 1973 in children with acute lymphoblastic leukaemias, the prevention and therapeutic possibilities were checked again. Chicken pox or herpes zoster convalescent sera being compatible for blood groups and zoster-immunoglobulin were not available. At the time of the epidemia the first reports on the effect of cytarabine (Alexan) were published. Moreover, we received an information on the therapeutic application of small pox vaccine inactivated with formaldehyde (vaccinia antigen) in adults with herpes zoster and herpes labialis. From 10 children with leukaemias, who were affected with chicken pox or herpes zoster, 7 received up to 1.0 ml of inactivated small pox vaccine intramuscularly on the first day of manifestation. In 6 of the patients there were no new efflorescences on the third day. A third child died. First of all it seems probable that this influence may be due to an induction of interferon formation. Further studies will have to elucidate to what extent this mechanism will also be efficient in severe cases of immunosuppression.


[The transplantability of bone marrow and spleen cells after filtration through silon tissue]. Investigations were carried out on the separation of haematopoietic stem cells from suspensions of the bone-marrow and spleen by means of filtration with silon tissue. The presence of stem cells in the filtrates was determined by the spleen colony test according to the method of Till and McCulloch in irradiated mice. The investigations revealed that a selective separation of haematopoietic stem cells could not be achieved when proceeding in this way. From the results of further test series, in which suspensions were also used which had been gained from haematopoietic tissues of hypersplenic mice, the conclusion could be drawn that the haematopoietic stem cells obtained by filtrating the bone-marrow will have another affinity to the spleen tissue of irradiated mice than the haematopoietic stem cells gained by filtrating the spleen tissue.


Inhibition of normal granulopoiesis by cytostatic agents. Rabbits were treated with cyclophosphamide and 5-fluorouracil, myelosuppressive cytostatic agents, applied with a single dose of 1/3 LD50 or daily doses of 1/30 LD50 given for 14 days. Functional tests for evaluation of granulopoiesis were regularly performed at standard intervals and were following: leukocytosis, bone marrow picture with mitotic index, 3H-thymidine incorporation in vitro followed by autoradiography of labeled promyelocytes and myelocytes, serum lysozyme activity, mobilization of granulocyte reserve pool by staphylococcal alpha-toxin, cytochemistry of granulocytes, phagocytosis ability and Nitro-BT reduction. It has been found that 6-10 days after application of cytostatics, a marked depression of proliferation of young granulocyte forms and lowered reserve pool, are regularly observed. This was followed by spontaneous regeneration of granulopoiesis. No changes were noted in functional tests of mature granulocytes in peripheral blood. It is suggested that for investigation of the impairment of granulopoiesis after application of cytostatic agents, most suitable is evaluation of mobilization of the bone marrow reserve pool, lysozyme activity in blood serum and labelling of promyelocytes and myelocytes with 3H-thymidine in vitro.


[Blood morphology of the European eel (Anguilla anguilla). II. Studies on granulopoiesis]. It was found that the granulocytes for Anguilla anguilla mainly form in the kidney. The stem cell of granulocytes is the large hemocytoblast. Sequences of development were established for the heterophil, cosinophil and basophil granulocytes. Myeloblasts, promyelocytes, metamyelocytes, mature red-shaped and segmented forms were described as stages of development of the heterophil granulocytes. In the case of the eosinophil and basophil granulocytes the myeloblastic and myelocytic stages could be demonstrated as well as the mature granulocyte. By the aid of special granular staining, phase contrast observations, supravital and cytochemical investigations the granulocytes could be described. The cytochemical proof for the granulocytes delivered a distribution pattern of the lipids, carbohydrates, RNA (RNS) and enzymes: unspecific esterase, alkaline and acid phosphatases, oxydase and peroxydase. By means of heart puncture a larger loss of blood was caused and the hematopoiesis stimulated. The following blood letting gave indications of how rapidly the granulopoiesis develops and how much time maturing takes. After a larger loss of blood the new-growth of the granulocytes will be completed nine days later.


[Behavior of the heparinocytes after gold therapy]. A reduction of the total leukocytes as well as a significant decrease of heparinocytes and BAI (basophilic age index) can be observed in rheumatoid arthritis in the course of a gold therapy. As some coagulation parameters simultaneously speak in favour of an enhancement of the intravasal coagulation, a partial blocking of the endogenous heparin caused by gold may be supposed. A combined heparin or heparinoid therapy in a low dosage is being recommended for risk patients of the vascular and coagulation system.


[Thrombocyte kinetics before and after gold therapy in rheumatoid arthritis]. Before and after performing a basic therapy with sanocrysin, thromboytic kinetic examinations were carried out in 12 patients suffering from rheumatoid arthritis. The thrombocyte survival time, maximal recovery and thrombocyte turnover were determined. The surface activity values were given in the form of spleen-heart quotients and liver-heart quotients as well as by surplus impulses over these organs. The findings evaluated statistically reveal that even the untreated rheumatoid arthritis will have thrombocytic kinetics deviating from the norm. By influencing RES the gold treatment will lead to an reduction of the enhanced platelet decomposition. The behaviour of single parameters before and after gold therapy are discussed. The examination of thrombocyte kinetic could not identify a damage of thrombopoiesis in the bone-marrow and in the periphery caused by sanocrysin.


[Fibrinolysis before and after gold therapy in rheumatoid arthritis]. In 12 patients with chronic rheumatoid arthritis the immunoglobulins IgG, IgA and IgM were determined according to Mancini and the fibrinolytic split products according to Nilehn before and after a gold treatment of 3 to 6 months. The IgG values were always increased and even after the treatment there was only little regression. The fibrinolytic split products found in 5 cases speak in favour of an enhanced intravasal coagulation, which increased still further after the gold therapy. In spite of clinical improvement the immunological processes and latent actions of coagulation seem to pass almost undiminished.


[Effect of gold therapy in rheumatoid arthritis on leukopoiesis and granulocyte phagocytosis]. In 12 patients with rheumatoid arthritis the investigations of leukopoiesis and granulocytic phagocytosis were carried out before and after a gold therapy. A marked reduction of granulocytic phagocytosis could be observed here which decreased after the gold therapy, yet remained below the values of a normal collective. Partly contrary informations are discussed. The disturbance of the phagocytosis capacity of granulocytes may possibly be due to a rheumatic factor.


Changes in erythropoiesis during the course of polycythaemia vera. Using 58Fe, 51Cr and cytological parameters, the authors have examined erythropoiesis in 44 polycythaemia vera patients diagnosed as such on the basis of the usual parameters (exept for determination of the erythropoietin level). In the patients divided into four types the following characteristica were observed. In type I, increased erythropoiesis is evident by accelerated plasma iron clearance, greater PIT and EIT as well as enhanced iron utilization and production indices. In type II, in addition to the former signs of increased erythropoiesis moderately shortened red cell life-span and hyposideraemia characteristic of splenic sequestration and resulting from bleeding and blood letting seem to be accompanied by microcytosis. There is a metaplastic erythropoiesis in type III, bone marrow activity decreases, but the increased erythropoiesis is indicated by several parameters already observed earlier. At the time the iron utilization indicative of effective erythropoiesis is decreased, thus ineffective erythropoiesis and considerably shortened red cell life-span are responsible for the enhanced iron turnover. This is also shown by the regression calculations. In type IV effective erythropoiesis was considerably decreased in the patients with severe anaemia. Sings which are indicative of metaplastic erythropoiesis are absent. In one of the patients the morphological changes characteristic of dyserythropoiesis were found. Although all our patients were given treatment. We believe that these alterations in the character of erythropoiesis are not likely to be the consequences of therapy.


[Production of an enriched factor VIII reagent]. An enriched factor VIII preparation was produced from cryoprecipitates by means of dextran. Cleaning was made in two phases: In the first phase the fibrinogen was precipitated and in the subsequent second phase the same was done with antihaemophilic globulin. By comparing the quantity and the degree of enrichment gained from the precipitation with dextran and with polyaethylenglycol, the conclusion can be made that both procedures virtually lead to the same results.


The "echis carinatus venom" prothrombin assay in coumarin treated patients. A comparison with one-stage and immunological assays. Prothrombin (factor II) was assayed in a group of coumarin treated patients using the Echis carinatus venom as thromboplastin. The levels obtained were comparable to those observed using the classical one-stage method. A good correlation was in fact observed between the two methods. The levels observed by the Echis carinatus method were definitely lower than those obtained using two immunological methods indicating that Echis carinatus venom activated, in our system, only normal prothrombin. However, even the levels obtained immunologically were slightly decreased, regardless of the method used, as compared to pooled normal plasma. In congenital prothrombin deficiency (homozygotes and heterozygotes) the level obtained by the Echis carinatus method was comparable to that observed by the one-stage method. On the contrary, in a congenital dysprothrombinemia (prothrombin Padua) a normal level was observed whereas the one-stage and two-stage methods yielded constantly levels of about 50% of normal.


[Results in the treatment of immune thrombocytolytic purpura (ITP)]. The late results in the treatment of 43 patients (adults) with chronic idiopathic thrombocytopenic purpura (ITP) are represented. Steroid treatment proved to be excellent and well-efficient in 20% of all cases and splenectomy in 70% of all cases. The good, but temporary increase of thrombocytes observed after the preceding steroid medication and the thrombocytosis after splenectomy can be explained as a favourable prognostic sign for a lasting success after the operation.


[Determination of the thrombocyte count in platelet-rich plasma]. A method is described according to which the number of thrombocytes may be calculated from the optical density of plasma enriched with platelets. The accuracy of the method is ensured by statistical calculations. Citrate venous blood of 60 surgical patients was used for the measurements.


[The appearance of anti-thrombocyte and anti-leukocyte antibodies in hemophilia A patients after cryoprecipitate transfusions]. 18 sera of haemophilia-A patients were examined for the presence of antithrombocytic and antileukocytic antibodies. It was only in a very small number of test persons (5) that antibodies could be found, though a variety of cryoprecipitate transfusions had preceded. The causes are discusses. The correlation existing between the presence of antibodies and the appearance of transfusion reactions is refferred to.


[Studies on the effect of various kinds of cytostatic therapy on the cellular immune reaction in children with acute lymphatic leukemia]. Clinical and experimental findings on possible changes of the lymphocyte function during an immunosuppressive or cytostatic therapy respectively caused investigations to be made for explaining the connections existing between the influence of cellular immunoreaction and the use of different cytostatic regimes. Earlier findings on the influence of cellular immunoreaction after adding cytostatics to cultivated cells and investigations on the influence of the lymphocyte function in dependence on cytostatic therapy were used for comparison. Transformation and mitosis rates as well as necrosis rates and the result of macrophage migration inhibition are comparable parameters for influencing the lymphocyte function in children treated with cytostatics. Antimetabolites, vincristine, asparaginase and daunomycin will have less influence on the transformation rate as an expression of an immunosuppressive effect on only those cells responding in accordance with their kinetic phase. Cyclophosphamide will inhibit the transformation reaction more significantly. Examinations in children with different therapeutic regimes reveal a certain validity of therapy after the first statistical evaluation of the clinical material.


[Effect of immunotherapy on lymphocyte function in acute lymphatic leukemia]. During the immunotherapy children suffered from acute leukaemias will have a significantly higher transformation rate than at the beginning of the immunotherapy. This may be explained by an increase of the immunological competence as well as by an enhanced mobilization of lymphatic cells. Leukaemic blasts used for immunoinduction-therapy will have no higher transformation rates as antigens than those cells never contacted by children. During the immunotherapy an increase of transformation rates may be observed after administering unspecific antigens and in mixed cultures. In a retrospective manner the indication for immunotherapy may be checked again in children with immunotherapy on the basis of the clinical course and evaluation of the cellular immunoreaction.


[The problem of capability for antibody formation in juvenile acute leukemia]. A report is presented on the quantitative behaviour of immunoglobulins G, A and M in 105 children with acute lymphatic leukaemia. Those 24 cases with a "total" hypoimmunoglobulinaemia referring to all three main classes are particularly analysed. Initially hyperplastic forms of leukaemia had primarily lower Ig-levels and a considerably worse prognosis.


[Cytogenetic studies as a contribution to the diagnosis of juvenile preleukemia and leukemia recurrence]. Hematologic changes in panmyelopathia are characterized by a wide-spreading spectrum of symptoms and a rare specifity. Therefore cytological and cytochemical findings do not allow a significant prognosis for the malignant or benign development of panmyelopathia. Cytogenetic experiments showed only the Philadelphia chromosome being of diagnostic value. MEISNER and co-workers, who studied adults with panmyelopathia and proven myelocytic leukemia and 5 children with acute lymphocytic leukemia, found that significant and persistent spontaneous division in unstimulated 24 hr. peripheral blood cultures is an indication of a malignant state. The present work shows that in two of five children with panmyelopathia and with significant spontaneous division chronic myelocytic leukemia developed or was in the very initial state; a third child with spontaneous division is still under control. In contrast to literature only one of 14 children with ALL had significant spontaneous cell division. Therefore the method applied must be checked for its usefulness in ALL and especially for its usefulness in early recognition of a relapse.


[Clinical and cytological differences in adult acute lymphatic and acute undifferentiated leukemia]. The usefulness for clinical purposes of the distinction of acute undifferentiated (AUL) and acute lymphocytic leukemia (ALL) is suggested by the following observations: 1. Maturation from AUL to ALL has not been observed. Transformation of ALL to AUL has been reported i.e. less of cytoplasmic polysaccharides; however this seems rather to be the effect of cytotoxic therapy and not a real change of the cytological type. 2. Significant differences among ALL and AUL can be noted as far as the therapeutic response is concerned: All of the 9 patients with ALL but only 2 out of 9 patients with AUL went into remission. The mean survival of the cases with ALL amounts to 34, that of AUL only to 4 months. Out of the patients with ALL 4 patients are still alive in persistant first remission after 77, 57, 36 and 28 months. 3. ALL occurs most frequently in young adults (mean age of 21 patients: 31.7 years): AUL is more frequent in elderly patients (Mean age of 18 patients: 57.6 years). 4. In our material ALL did never occur consequent to a typical preluekemic stage, which was followed either by myeloblastic, monocytic, erythroleukemic or undifferentiated leukemias.


[The effect of exogenous alkalization on cytokinetics and on the survival rate of mice with lymphoblastic leukemia]. In mice vaccinated with two forms of lymphoblastic leukaemia and alkalized with intravenous administration of sodium bicarbonate, the survival rate, the extent of leukaemic infiltration and the proliferative capacity of cells in the bone-marrow, thymus, spleen, lymphnodes, liver and lungs were investigated. The survival rate in the TAL leukaemia of the AKR stem producing an endogenous acidosis could be significantly prolonged in a statistical way by alkalization. Yet an accelerated expiring rate could be observed after exogenous alkalization in L-1210 leukaemia of the DBA/2J stem producing an endogenous alkalosis. By means of cytological and impulse-cytophotometrical investigations the exogenous alkalization of both forms of leukaemia could be proved to have a direct bearing on the proliferative kinetics. In TAL leukaemia the leukaemic proliferation was inhibited by the exogenously involved correction of the acid-base balance; in the L-1210 leukaemia, however, the pH disturbances were enhanced, thus accelerating the leukaemic proliferation. Consequently, the disturbances of the acid base balance seem to be an essential cofactor in the leukaemia genesis. The exogenous direction of the acid-base balance may be important as a means of treating leukaemia.


[Prefinal clinical findings and results of autopsy in 82 children with acute lymphatic leuckemia (ALL) under various courses of therapy]. At present 80...90 % of the patients with acute lymphatic leukaemia die in the blastic crisis. About 10% will come ad finem during full remission caused by side effects of the treatment and their complication. The leukaemic terminal crisis may be accompanied or overlapped by a number of complications, the most frequent among own patients being acute bleeding in the terminal phase. First of all the source of bleeding is to be found in the gastro-intestinal tract (80%). Other authors found infections to be the most frequent final cause of death. It is only under autopsy that leukaemic infiltrates, infections and bleeding are completely recognized to their full extent. After polychemo-therapy the patients showed a significant increase of complications including pulmonary oedema and a marked insufficiency of the bone-marrow with leukocytopenia and granulocytopenia in the peripheral blood. Among the biochemical parameters only a generally significant increase of alpha2 and gamma globulins could be found in the serum. A correlation towards a form of therapy could not be ensured.


[The spontaneous lymphocyte transformation rate in newborn infants at risk]. The lymphocyte transformation test was performed in 32 risk newborns and 32 comparative persons (17 adults, 15 children). In the void controls without antigen addition the newborns had a significantly higher spontaneous blastic reaction than the control group. The phenomenon may be explained by lymphatic stem cells in the blood or an ontogenetically higher content of "embryonic tissue" respectively being present as unspecific stimulant or an immunological defence reaction against maternal immunoglobulins transmitted diaplacentally (formation of antigammaglobulin factors) or against maternal lymphocytes to prevent a "runt disease".


The human blood platelet: its derivation from the red blood cell. A morphologic study. The blood platelet arises from the interior of the red blood cell when blood is either damaged or disturbed. The platelet body may be seen to form from an amorphous granular mass to a definite granular platelet body when blood is prevented from coagulating by the use of a retardant solution.


[The relevance of schizocyte demonstration for the diagnosis of rejection in patients with transplanted kidneys]. Schizocytes may be obtained, if erythrocytes are being pressed through glassfibre threads under pressure. For the purpose of explaining the different mechanisms of schizocytes origin, model tests were made in the haemoresistometer according to Fleisch and in the shaking water bath. As schizocytes can easily be identified, they will yield valuable differential-diagnostical informations and will give a high evidence in checking the progress of transplanted patients.


[The correlation of human erythrocyte shape with dark-field light scattering intensity]. This study was concerned with the quantitative evaluation of dark field light scattering by sedimented erythrocytes of banked human blood samples. Due to considerable variability of both appearance and amount of scattered light the discocyte group had to be subdivided into discocyte I and discocyte II. The mean intensity of scattered light increased about three fold from discocyte II to echinocytes I, II, III, sphaeroechinocyte, and sphaerocyte. On the other hand the average light scattering intensity of discocytes I exceeded that of discocytes II about 2.5 times, with individual data varying over a wide range. There was a rapid disappearing of discocytes I correlated with time of storage. Therefore it is concluded that discocytes I represent the initial stage of erythrocytes transforming under banking conditions.


["Sugar-agglutinability"].

["Sugar-agglutinability"]. Haemagglutination induced by saccharose is shown to go parallel with a binding of autologous isohaemagglutinin to the surface of erythrocytes. Under suitable conditions, i.e. in the presence of anorganic ions and health, haemagglutinin may be largely separated from the cell surface and the saccharose agglutination may be inhibited. Haemagglutination induced by saccharose will re-appear after agglutinins being re-adsorbed at low incubation temperatures and prolonged incubation time in non-ional as well as ional media. Therefore it is assumed that in the inert non-ional atmosphere the autologous haemagglutinin will produce a phenomenon of agglutination in non-homologous erythrocytes similar to that in homologous cells.


Iron absorption in gastric and duodenal pathology in patients with iron deficiency anaemias. Absorption of radioactive iron was studied in 87 patients with different types of iron deficiency anaemias and in 23 healthy subjects. The subjects were given 1...2muci of radiactive iron in the form of FeSO4 together with 5 mg of nonradioactive iron as a carrier and 100 to 150 g of white bread, radioactivity on the whole body being studied with a big liquid scintillation counter 4 pi (BLSC-2). In clinical observations and in single experiments on volunteers there was no conformity of the values of absorption with the levels of acid-formation. But in the same time the gastric juice from an anaemic horse almost doubled iron absorption in healthy individuals. Marked morphological changes in the gastric mucosa inhibited the absorption in the intestine and the degree of increase of absorption in patients with anaemia depended to some extent on the morphological conditions of the gastric mucosa. When healthy subjects and patients with iron deficiency anaemia were given bread "enriched" with iron before baking instead of common bread with "external" mark there was observed similar correlation between the values of absorption but the figures were somewhat lower.


Hb Lepore and (haemo-) blastomata.

Hb Lepore and (haemo-) blastomata. The still increasing amount of carriers and anemics by thalassemia (Th) and other Hb-pathies (approximately 4,000 among approximately 48,000 investigated people) have shown that Campania is the most affected world area by all Hb Lepre conditions. Among 161 people with heterozygous Hb Lepore we have noticed 10 cases associated with (hemo-) blastomata as follows: 2 Chr. Lymphatic Leukemia, 2 Ac. Lymphoblastic Leukemia, 1 Lymphosarcom, 1 Colon Cancer, 1 Uterin Cancer, 1 Plasmocytom, 1 Hodkgin Disease, 1 Ac. Promyelocyte Leukemia (or fatal ac. agranulocytemia?). In the literature we recently found 2 other similar cases. The incidence of such malignancies in our Hb Lepore people reaches 6%. On the contrary in the heterozygous Th. group, among 3,150 carriers, we diagnosed only 20 people with (hemo-) blastomata as follows: 12 Ac. Leukemia (9Lymphoblastic) and 8 Chr. Myeloid Leukemia, with  an incidence rate of 0.6% namely a little higher than in normal people. This highly significant discrepancy rate shows an elective predisposition to (haemo-) blastomata from Leporian people.


[Autologous transfusion of erythrocytes with high or low concentration of 2,3-diphosphoglycerate. Survival rate and time and hemoglobin-oxygen affinity]. 1. In human erythrocytes the 2.3 DPG concentration was increased three to fourfold of the norm as IPP re-suspension by an incubation time of four hours at 37 degrees C or as ACD-AG blood was lowered below 20% of the norm respectively. After an autologous transfusion the 24 hours' surviving rate and the apparent half survival time of cells as well as the affinity of haemoglobin to oxygen in the total blood were measured. 2. The 24 hours' surviving rate for fresh erythrocytes with increased 2.3 DPG and ATP concentration amounts to 73% and the apparent half survival time amounts to 6 days. If erythrocytes are stored for four weeks as IPP resuspension at 4 degrees C, the 24 hours' surviving rate is 59%. Erythrocytes from fresh ACD-AG blood with lowered 2.3 DPG and a normal ATP concentration have a 24 hours' surviving time of 85% and an apparent half survival time of 24 days. 3. After autologous transfusion of 400 ml of erythrocytes with increased 2.3 DPG concentration the P50 value of the total blood will increase by 3 mm of Hg, after administering 400 ml of erythrocytes with lowered 2.3 DPG concentration it will fall by 1.8 mm of Hg. 4. The findings are discussed in connection with the significance of the changes of affinity of haemoglobin to oxygen produced by 2.3 DPG for the oxygen supply of tissues and under the aspect of using stored blood with increased 2.3 DPG concentration for practical purposes.


[Studies on the demonstration of a factor VIII or IX deficiency by means of partial thromboplastin time]. A report is presented on the performance of the correction of PTT by means of factor VIII and IX deficiency plasma, which may be used at least one year, when preserved in liquid nitrogen. The method allows reliable, qualitative statements to be made about disturbances in the area of the coagulation factors VIII, IX, XI and XII; the small amount of time required for preparing and carrying out these works representing an essential advantage.


Isolation of Non-modified gamma globulin for intravenous use. The availibility of a non-modified gamma globulin for intravenous use should abolish the intramuscular administration of Cohn standard gamma globulin and replace modified products to the greatest possible extent. The product developed in our institute is purified from Cohn fraction II using HES and aluminum silicate for the elimination of aggregates. The product shows excellent purity, stability, and clinical compatibility.


Chromosomal analysis of the pygmy chimpanzee (Pan paniscus) with a comparison to man. The karyotype of Pan paniscus is reexamined by G-banding and examined for the first time by C-banding. In addition, examination of the chromosomes by the use of the fluorochromes adreamycine and 33258 Hoechst is undertaken. C-banding showed a surprising pattern with numerous terminal C-bands, as interstitial C-band, and several chromosomes lacking C-bands. Polymorphic conditions for C-bands are also identified involving several pairs. In a comparison to the chromosomes of man, G-banding revealed two pericentric inversions not previously observed. Only chromosome pairs No. 9,11,12 and the X are similar to man's by all techniques employed.


[Bleomycin-induced lung changes in the roentgen picture]. Amongst 25 patients treated with Bleomycin for squamous epitheliomas, irreversible pulmonary fibrosis was observed in four cases and reversible fibrosis in two others. The radiological changes in five patients consisted of linear interstitial shadows and one patient showed nodular shadowing. By means of lung biopsies, these findings were related to the pathological changes. Problems in the differential diagnosis of these radiological findings are discussed.


A histochemical study of the tracheobronchial epithelial mucosubstances in normal dogs and dogs with chronic bronchitis. The tracheobronchial mucosubstances in a group of normal dogs and a group of dogs with chronic bronchitis have been characterized histochemically. Sulphomucin was the predominant mucosubstance in the epithelial goblet cells of normal dogs and a mixture of sulphomucin and sialomucin was found in the bronchial glands. In the dogs with chronic bronchitis there was a shift towards the production of sialomucin in both sites.


[Determination of normal values by means of various statistical methods derived from radioiodine tests (author's transl)]. Normal values derived from 361 euthyroid patients were calculated by means of five different statistical methods and compared. Borderline values were also obtained from 61 patients with hyperthyroidism, nine with hypothyroidism and ten with autonomous adenomas. The following individuals data were collected: 131 I-PBI after 48 hours, thyroid uptake after two, 24 and 48 hours.


[Clinical aspects of bronchial cancer].

[Clinical aspects of bronchial cancer]. The most frequent cause of death of the male is cancer of the lungs. The prognosis is still unfavourable. The cases of patients having survived for 5 years amount altogether to not more than 5%, as far as operated patients are concerned, the quota amounts to 20-25%; in cases of early detection of cancer, however, the rates are up to 40%. Precaution and preventive care (reduction of cigarette consumption) is at present not possible. Considerable time is being wasted because of the uncharacteristic and gradually proceeding symptoms and misinterpretations of the X-ray findings. The bronchial carcinoma can imitate any other disease of the lungs. Even a normal X-ray picture does not exclude carcinoma. The observation of acute symptoms appearing for the first time and of those already existing, but changing suddenly, is essential. Exclusive treatments are dangerous. Any X-ray finding of the lungs should be followed up to all bronchological details. A "normal" X-ray picture, accompanied by clinical symptoms, requires basic diagnostic measures including bronchoscopy.


Protein measurements in the early prenatal diagnosis of spina bifida. Measurement of beta-lipoprotein concentration in amniotic fluid is introduced as a new parameter for the early prenatal diagnosis of spina bifida. It was successful in 15 cases of spinal bifida, but failed in 5 cases of open spina bifida and 2 cases of closed spina bifida. All assays were performed before the end of the second trimester and most between 15 and 20 weeks of pregnancy. beta-lipoprotein was compared with alpha-fetoprotein and alpha2-macroglobulin in its effectiveness in diagnosing spina bifida at an early enough date to allow a termination of pregnancy.


Influence of serum-derived chemotactic factors and bacterial products on human neutrophil chemotaxis. The chemotaxis of neutrophils has been shown to be modulated by serum factors, tissue factors, bacterial products, and a host of other substances. In vivo, these factors may act in concert with each other to modify neutrophil movement. We examined the effect of aggregated gamma globulin-activated serum (AS), bacterial factors, and endotoxin either alone or in combination with each other, on human neutrophil chemotaxis. Exposure of neutrophils to AS resulted in deactivation to AS but not to Escherichial coli or Staphylococcus epidermis culture filtrate. Exposure of neutrophils to S. epidermis or E. coli CF or E. coli endotoxin resulted in deactivation to AS or C5a but not to E. coli or S. epidermis culture filtrate. Addition of endotoxin to AS or C5a resulted in inhibition of chemotaxis by untreated neutrophils toward this combination as compared with AS alone. These results suggest that separate mechanisms may be involved when serum or bacterial chemotactic factors initiate human neutrophil chemotaxis. Furthermore, the potent but specific inhibitory effect of endotoxin on chemotaxis toward AS may be of clinical significance.


Characterization of the Madrid E strain of Rickettsia prowazekii purified by renografin density gradient centrifugation. The avirulent Madrid E strain of Rickettsia prowazekii cultivated in chicken yolk sacs could be purified successfully with a Renografin density gradient method developed previously for Rickettsia typhi. Recovery during purification, viability, and lack of contamination with host cell components were similar for the two species, although yields of R. prowazekii per yolk sac were lower. Purified typhus rickettsiae provided satisfactory antigens in the complement fixation, Ouchterlony double-diffusion, and microagglutination tests. The retention of the typhus soluble group antigen during purification was readily demonstrated by complement fixation tests. However, removal of the soluble group antigen by ether treatment was not always adequate for the demonstration of type-specific particulate antigens. Heat-killed R. prowazekii cells gave higher serum microagglutination titers than untreated or formalized cells, a difference was noted for R. typhi cells. Although the protein profiles of whole cells and extracts of R. typhi and R. prowazekii on sodium dodecyl sulfate-polyacrylamide gels were relatively similar, a small but reproducible, difference in the electrophoretic mobilities of their malate dehydrogenases was detected. Purification of typhus rickettsiae on Renografin gradients has no apparent adverse effects on their metabolic or antigenic properties.


Protein bound iodine levels during oestrus, pregnancy and non-pregnancy states in goats. Thyroidal function in goats as estimated by PBI values of blood serum showed a very high activity in oestrus, followed by that in pregnancy state. There was significant increase in PBI values between oestrus and non-pregnancy groups. The lack of significance between pregnancy and non-pregnancy values has been explained. Mean PBI values in oestrus, pregnancy and non-pregnancy were respectively 5.91, 5.31 and 3.74 mug/100 ml blood serum.


Characterization of membrane and cytoplasmic antigens of Mycoplasma arginini by two-dimensional (crossed) immunoelectrophoresis. Two-dimensional immunoelectrophoresis was employed to electrophoretically identify membrane and cytoplasmic antigens of Mycoplasma arginini G-230. Five distinct cytoplasmic antigens were observed in soluble fractions prepared by digitonin lysis with electrophoretic mobilities (relative to bovine albumin) ranging from 0.36 to 0.86; four of these were common to other M. arginini strains: leonis and 23243. Five membrane antigens were identified, two of which (0.4 and 0.2) were common to the other M. arginini strains. The most prominent antigenic component of the membrane fraction (the complex membrane antigen) was electrophoretically heterogeneous, showing four antigenically related components with electrophoretic mobilities of 1.2, 0.95 to 0.76 and 0.05. The complex membrane antigen was exposed on the outside of the mycoplasmic cell because absorption of antiserum with live organisms removed antibody to this component. Antibodies to two other membrane components (0.6 and 0.2) were removed by absorption with Triton-solubilized membranes, but not by untreated membranes, indicating that these components were, at best, little exposed on either membrane surface. Antiserum was prepared against the complex membrane antigen using precipitin lines from two dimensional electropherograms as the immunogen. This antiserum reacted only with the complex membrane antigen and did not react with the other M. arginini strains, indicating that the complex membrane antigen was unique to strain G-230.


Solid-phase radioimmunoassay as a method for evaluating antigenic differences in type A influenza viruses. An indirect solid-phase radioimmunoassay (RIA) procedure was developed to determine its usefulness in assessing antigenic variation in the surface antigens of type A influenza virus strains. The importance of several test variables was examined, and those having a significant effect on the binding ratios were identified. The reproducibility of the RIA procedure was investigated. Maximum variation of the mean binding ratios encountered in repetitive tests was found to be approximately 20%. The antigenic characteristics of the A/Aichi/68 virus strain were compared with several different type A virus strains. Utilizing anti-A/Aichi/68 immune serum together with specific anti-hemagglutinin and antineuraminidase immune sera, the RIA method was shown to quantitatively differentiate the surface antigens of the A/Aichi/68 virus strain from the surface antigens of the type A strains that preceded, as well as from those that succeeded, the introduction of the Aichi virus strain in 1968. Using antigen-specific serum, both the hemagglutinin and neuraminidase antigens can be independently characterized in one test system. This advantage, together with the ease and greater sensitivity of the RIA, should make it a useful serological test for evaluating antigenic variation of type A influenza viruses.


Cellular origin of interferon induced by bacterial lipopolysaccharide. Bacterial lipopolysaccharide (LPS) induces interferons with different properties in mouse macrophages and B lymphocytes. Macrophage interferon is labile at 56 degrees C and is neutralized by anti-mouse fibroblast interferon at a dilution of 1:6,142. B cell interferon is more heat stable and is neutralized by the same antiserum only at a dilution of 1:276. Serum obtained early (1 h) after an intravenous injection of 100 mug of LPS resembled macrophage interferon, whereas serum obtained at later times resembled more and more B cell interferon. The diverse cellular origin of LPS-induced interferon may explain the broad hyporesponsiveness produced by LPS in animals.


Antigenic relatedness of glucosyltransferase enzymes from streptococcus mutans. The antigenic relationship of glucosyltransferases (GTF) produced by different serotypes of Streptococcus mutans was studied by using a functional inhibition assay. Rat, rabbit, or hamster immune fluids, directed to cell-associated or supernatant-derived GTF, were tested against ammonium sulfate-precipitated culture supernatants containing GTF from seven strains of S. mutans representing six different serotypes. An antigenic relationship was shown to exist among GTF from serotypes a, d, and g, since both rat and rabbit antisera directed to serotype a or g GTF inhibited GTF of serotypes d and g similarly and both antisera also inhibited serotype a GTF. Furthermore, serum inhibition patterns indicated that GTF of serotypes c and e, and possibly b, are antigenically related to each other, but are antigenically distinct from GTF of serotype a, d, or g. Serum antibody directed to antigens other than enzyme (e.g., serotype-specific antigen or teichoic acid) had little effect on the inhibition assay. Salivas from rats immunized with cell-associated or supernatant-derived GTF exhibited low but consistent inhibition of GTF activity, which generally corresponded to the serum patterns. The sera of two groups of hamsters immunized with GTF (serotype g), enriched either in water-insoluble or water-soluble glucan synthetic activity, gave patterns of inhibition quite similar to those seen with sera from more heterogenous cell-associated or crude supernatant-derived GTF preparations. Both groups of hamster sera also gave virtually identical patterns, suggesting that the two enzyme forms used as antigen share common antigenic determinants. The results from the three animal models suggest that among the cariogenic organisms tested, two (serotypes a, d, g and b, c, e), or perhaps three (serotypes a, d, g; b; and c, e), different subsets of GTF exist that have distinct antigenic determinants within a subset.


Detection of early antigens in nuclei of cells infected with cytomegalovirus or herpes simplex virus type 1 and 2 by anti-complement immunofluorescence, and use of a blocking assay to demonstrate their specificity. Skin fibroblasts exposed to cytosine arabinoside (Ara C) were infected with either cytomegalovirus (CMV) or herpes simplex virus (HSV) type 1 and 2. Herpesvirus-determined early antigens (HV-EA), detected by anti-complement immunofluorescence (ACIF), occurred primarily in the nucleic, and the specificity of these results was established by an ACIF blocking reaction using F(ab')2 fragments of human and hyperimmune reference sera. Direct tests with selected sera and cross-blocking experiments between early antigenic systems of CMV, HSV-1 and the Epstein-Barr virus (EBV) did not demonstrate common HV-EA.


Adsorption of naturally occurring polymers onto calcium oxalate crystal surfaces. The adsorption of proteins and mucopolysaccharides on calcium oxalate crystals was measured by solution depletion. Anionic protein adsorption was found to be sensitive to calcium ion concentration. Adsorption of fibrinogen was anomalously large in the presence of 0.01 M Ca2+. Adsorption of cationic protein (histone) was sensitive to oxalate ion concentration. A small alteration in adsorption of protein as a result of pH or temperature change was also observed. Plots of adsorption versus concentration were interpreted in terms of a Langmuir adsorption isotherm. The derived Langmuir adsorption parameters were then used to investigate the contribution of protein, by physical adsorpti, to the quantity of matrix in urinary stones. It was concluded that physical adsorption can account for the deposition of part but not all of the matrix in calcium oxalate stones. It was also concluded that physical adsorption of mucopolysaccharides by calcium oxalate crystals could explain the inhibition of growth and aggregation of calcium oxalate crystals seen with in vitro precipitation systems. Recalculation of published data indicates that adsorption of protein on dental enamel (calcium hydroxyapatite) results in approximately the same extent of surface coverage as adsorption on calcium oxalate crystals, but protein has a much lower affinity for dental enamel than for calcium oxalate crystals.


Induction of organ-specific antigens of the rabbit male accessory glands by injection of testosterone or gonadotrophin. Highly specific antiserums for two antigens of rabbit male accessory glands, called FII and FV, were used to study the effect of hormonal treatment on their appearance during postnatal development. Single or double serial injection of testosterone, or human chorionic gonadotrophin, produces an increase in accessory gland and testis weight, and at the same time induces the synthesis of a detectable amount of specific antigens. This was proved by using groups of animals 4 and 6 1/2 weeks old. The antigens were consistently absent in accessory glands from normal and control animals of the same age. The histologic characteristics of maturation were also observed. Ultrastructural studies revealed an increase in number of microvilli supranuclear vaculoes with secretory content and well developed rough endoplasmic reticulum. These changes were more easily detected in young animals treated with chorionic gonadotrophin. The significance of these findings is discussed in relation to the presence of specific carriers (cytosols).


Cardiac Arrhythmias in the horse.

Cardiac Arrhythmias in the horse. Electrocardiograms were obtained from normal horses and from horses with cardiac or other organic disease that affected the cardiac rhythm. Tracings were obtained from a base-apex bipolar monitor lead, with the negative electrode attached to the skin in the right jugular furrow and the positive electrode attached to the skin on the ventral medline, beneath the apex of the heart. Each arrhythmia was discussed relative to importance and probable cause.


Purification and properties of Rauscher leukemia virus DNA polymerase and selective inhibition of mammalian viral reverse transcriptase by inorganic phosphate. Rauscher leukemia virus RNA-directed DNA polymerase has been purified to near homogeneity (greater than 90% pure) using affinity chromatography on polycytidylate-agarose with over 85% recovery of input enzymatic activity. The purified enzyme has a molecular weight of approximately 70,000 and appears to consist of a single polypeptide chain. The enzyme is free of DNase, but has RNase H activity. Analysis of the requirements for optimal rates of DNA synthesis by this enzyme using synthetic and natural template-primers has revealed template-specific variations in such requirements. During these studies it was observed that DNA synthesis catalyzed by Rauscher leukemia virus DNA polymerase is inhibited by the addition of inorganic phosphate. An analysis of the mechanism of phosphate inhibition was carried out using the synthetic template-primer poly(A)-(dT)10. It appears that by some mechanism, possibly involving the substrate binding site of the enzyme, phosphate ions inhibit DNA synthesis with a more acute effect on the rate of chain growth than on that of initiation. The extension of these studies to DNA synthesis catalyzed by a variety of mammalian type C viral reverse transcriptases revealed that low levels ( less than or equal to 2 mM) of inorganic phosphate strongly inhibited DNA synthesis. The susceptibility to phosphate inhibition appears unique to mammalian type C viral enzymes since the type B viral enzyme, Escherichia coli DNA polymerase I, avian myeloblastosis virus and Mason Pfizer monkey tumor virus reverse transcriptase and cellular DNA polymerases alpha and gamma are not inhibited by inorganic phosphate. This phenomenon of phosphate inhibition of various DNA polymerases, therefore, provides a new basis for the differentiation of the sources and nature of these enzymes.


Structure of tetanus toxin. II. Toxin binding to ganglioside. The interaction between tetanus toxin and ganglioside containing 2 N-acetylneuraminic acid residues linked in sequence to one another has been investigated using a new method involving radioactively labeled ganglioside and tetanus toxin adsorbed to Sephadex matrix. Binding between the two components was demonstrated, and it was calculated that in the nanomolar concentration range, tetanus toxin becomes half-saturated at about 5 X 10(-8) M concentration of ganglioside. Removal of the ceramide portion from the ganglioside resulted in the complete loss of binding activity, whereas removal of the terminal N-acetylneuraminic acid residue from the intact ganglioside had no effect. Among the fragments derived from tetanus toxin (Helting, T. B., and Zwisler, O. (1977) J. Biol. Chem. 252, 187-193), only the heavy chain polypeptide exhibited a binding activity of the same order of magnitude as that observed for the native toxin. The light chain polypeptide showed no interaction with ganglioside and among the fragments derived from the toxin by digestion with papain, only Fragment C, at a high protein concentration, displayed marginal binding activity. Using monovalent antibodies directed against specific regions of the tetanus toxin molecule, it was demonstrated that antibodies directed against Fragment C uniquely interfere with the binding process. Anti-light chain serum was ineffective, as well as antitetanus toxoid serum previously absorbed with Fragment C. It is concluded that the binding site for ganglioside is located on the heavy chain portion of tetanus toxin, possibly in or near the region comprised by Fragment C.


[Cysts of the kidney in adults. Surgical approach]. 90 case records of renal cysts in adults submitted to surgery are studied. A simple pathological classification is proposed. The accompanying signs were, hematuria in 30 p. 100 of cases, but one should always seek another cause; renal colic is present in 22 p. 100 of cases, a palpable tumour in 50 p. 100, on the other hand, infection of the cyst is rare. 35 p. 100 of the cysts were associated with another disease, usually obstructive uropathy, and there were 3 cases of association with carcinoma of the kidney in this series. Pre-operative diagnosis, eliminating carcinoma of the kidney, was ensured by intravenous urography and echotomography which permitted us to restrict the indications for arteriography and aspiration of the cyst. Surgical treatment permits resection of the salient dome of the cyst in the absence of general contra-indications, in order to suppress symptoms due to the cyst and above all, eliminate carcinoma of the kidney. The post-operative period was uneventful and the mortality nil.


Formation of 5alpha-androstane-3alpha,17beta-diol by normal and hypertrophic human prostate. The 3-keto reduction of [1,2-3H]dihydrotestosterone to 3alpha- and 3beta-androstanediols was assessed in homogenates of 40 prostates obtained either at surgery or at medicolegal autopsy from men who had died suddenly. Formation of both androstanediols was demonstrable in cytosol and in microsomes, and both NADH and NADPH were effective cofactors for the two reactions. Formation of the two steroids was not influenced by storage of the gland for up to 8 h prior to processing. When NADPH was cofactor, the formation of 3alpha- and 3beta-androstanediol was significantly higher in microsomes and cytosol from hypertrophic than from normal glands.


Living histamine-containing cells from the bronchial lumens of humans. Description and comparison of histamine content with cells of rhesus monkeys. Cell populations obtained by bronchial lavage from human subjects were examined for the presence of cells related to the mast cell-basophil series. Such bronchial lumen histamine-containing cells (BLHCC) were identified. The BLHCC stained with toluidine blue may be identified by bright field or dark field microscopy. The BLHCC are alive as evidenced by ability to release histamine (H) after exposure to anti-IgE or calcium ionophore. Although H release from peripheral blood leukocytes by these two agents is potentiated by the presence of D2O, H release from BLHCC of the same subjects by anti-IgE or calcium ionophore was not potentiated by D2O. In studies comparing bronchial cell populations of humans and rhesus monkeys with peripheral blood leukocyte populations of the same subjects, the histamine content of the bronchial cell population was much higher in rhesus monkeys. IgE/Alb ratios of respiratory secretions and serum of the same human subjects were of the same order of magnitude in contrast to previous comparisons done on these fluids in rhesus monkeys.