[Eosinophil granuloma of bones. Report of 15 cases including 10 survivals with an average follow up of 4 years (author's transl)].

The bony form of eosinophil granuloma in histocytosis X, raises diagnostic and prognostic problems for the surgeon. 15 cases are reported here which permitted the authors to perform a rapid general review of this disease and judge its course as 10 patients were followed up with a minimum follow up period of 4 years. These observations confirm: --that the local course is always spontaneously favourable: --that the risk of a passage from an extra-bony form of histiocytosis X, should be considered all the more serious when the subject is younger, when there exist certain localisations, such as the mastoid, where there are certain general clinical signs or biological disturbances. Apart from exceptional symptomatic treatment, such as spinal decompression or treatment of a spontaneous fracture, the essential stage of clinical examination is biopsy. Medical treatments do not seem to have any influence on the bony lesion and are not without risk (radiotherapy). Although depending on various criteria, the prognosis should always be reserved and the patient should be followed up for a long period.


[Surgical treatment of acute hemorrhagic pancreatitis. Report of 75 cases. (author's transl)].

Out of 75 definite cases of acute hemorrhagic pancreatitis, 39 were associated with a biliary lesion of which 16 were definitively the cause of the pancreatitis (11 embedded gall stones = 1/5th of the gall stones embedded in the ampulla of Vater and producing acute hemorrhagic pancreatitis). The biliary pancreatites were twice as severe as the primary pancreatites. This justifies the emergency exploration of the bile duct in any case of severe pancreatitis, suggesting acute hemorrhagic pancreatitis. The course of the disease is unforeseeable, certain large hematomas may become reabsorbed without sequelae. Thus one should be very circumspect concerning evaluation of the lesions during the first two weeks. This is why we reject any removal of pancreatic tissue during the first two or three weeks.  We noted 30 deaths out of 70 cases of acute hemorrhagic pancreatitis during the postoperative period, 19 occurred during the first week. Concerning the 11 other deaths, they were in 9 cases very severe cases of acute hemorrhagic pancreatitis. Out of 41 cures, only 11 required secondary sequestrectomy, the 30 others were obtained without reoperation, often in spite of a large hematoma and clinical signs of severity. Our present attitude includes emergency operation of any severe case of pancreatitis in order to seek a biliary lesion with cholecystectomy (certain non-palpable calculi were thus discovered), radiomanometry of the common bile duct and, if necessary, sphincterotomy. The second operation is not always necessary, it should be carried out as late as possible after the 3rd week, sequestrectomy which is generally easy, may be carried out electively and under greater conditions of safety than necrosectomy or pancreatectomy.


[A rare case of acute bleeding from a stress colon. Etiology, pathogenesis and treatment (author's transl)].

The authors describe an exceptional case of acute hemorrhagic ulcer of the colon occurring after stress, emphasising the importance of mesenteric arteriography in the diagnosis and suggesting emergency resection in the treatment of such a case.


[Late ileal metastases from a skin melanoma with mainly hemorrhagic symptoms. Report of one case (author's transl)].

Intestinal metastase from a malignant melanoma are rare and raise difficult diagnostic problems especially when far from the initial tumour. Although acute intussusception is the usual clinical presentation, one should recognise the possibility of atypical symptoms: e.g. repeated digestive hemorrhage or resistant anemia. A sutdy of past history may lead to the discovery of a malanoma. Treatment is unfortunately surgical and palliative to releave the complication.


Inhibition of human lymphocyte-mediated mitogen-induced cytotoxicity of murine L-929 cells by heterologous anti-human lymphotoxin antisera in vitro.

Heterologous anti-human lymphotoxin (LT) antisera have been employed to investigate the role of LT in mitogen-(Con-A, PHA) induced destruction of murine L-929 cells by human lymphocytes in vitro. These various antisera will effectively neutralize human LT molecules associated with the stable (70 to 90,000 dalton) alpha-LT class of cytotoxin (anti-alpha-LT), the more unstable (35 to 50,000 dalton) beta-LT class of cytotoxins (anti-beta-LT), and antisera which will neutralize all classes of these cytotoxins in vitro, anti-whole supernatant (anti-W.S.). These anti-LT sera will greatly inhibit lysis of L-929 cells by using mitogen-activated human effector lymphocytes in vitro. This blocking was shown to be mediated by whole serum, purified IgG, or IgG-Fab fragments, which had been extensively absorbed with bovine serum, human serum, mitogens, and normal human lymphocytes. Inhibition of lysis was not apparently due to interference with either lymphocyte-target cell contact or lymphocyte activation step(s). The blocking effects of these sera were also shown to occur during the lymphocyte-independent phase of the lytic reaction. These data support the concept that the lymphocyte deposits an LT-like effector molecule on the target-L cell surface during the lymphocyte-dependent phase, which mediates cell lysis at a later time during the lymphocyte-independent phase.


The in vitro antibody response to cell surface antigens. I. The xenogeneic response to human leukemia cells.

An in vitro spleen fragment culture system has been developed for the production and analysis of xenogeneic antibody responses to cell surface antigens. Depending on the methods of immunization and in vitro stimulation employed, mouse spleen fragments can produce antibody of both IgG and IgM classes directed against human cell surface antigens for more than 30 days in culture. A saturation binding analysis of the antibody products indicates that their range of specificities was more restricted than that of serum antibody. Approximately 5% of the in vitro antibody products raised against a homogeneous population of human leukemia cells could distinguish between the antigens present on the leukemia cells and those present on normal human lymphocytes. Methods previously employed to influence the range of serum antibodies expressed against complex immunogens, such as suppression of certain responses by passive administration of antibody at the time of immunization, were tested in the in vitro spleen culture system and resulted in successful modulation of the antibody response patterns observed.


The in vitro antibody response to cell surface antigens. II. Monoclonal antibodies to human leukemia cells.

A method has been developed for the production of monoclonal mouse antibody responses in vitro against human cell surface antigens. Limiting numbers of immune spleen cells were transferred to syngeneic, irradiated recipients whose spleen fragments were then cultured in vitro and stimulated to produce antibody. The majority of the antibody from any one fragment culture was likely to be the product of a single donor B cell and thus monoclonal. Evidence for this included a linear relationship between donor cell transferred and spleen fragments producing antibody, extremely restricted isoelectric focusing patterns of the individual antibody products, and unique reactivity patterns of these antibodies against a panel of human lymphoid cells. Different human B leukemia cells were seen as immunogenically distinct by the mouse. By using the monoclonal mouse antibodies as probes, a fine analysis of cell surface antigens is jow possible.


Distribution of terminal deoxynucleotidyl transferase in bovine serum albumin gradient-fractionated thymocytes and bone marrow cells of normal and leukemic mice.

The distribution of terminal deoxynucleotidyl transferase (TdT) peaks I and II, in single cell suspensions of thymuses, bone marrow, and peripheral lymphoid organs fractionated in discontinuous bovine serum albumin gradients, was examined in a variety of mouse strains and Fischer 344 rats to relate the normal patterns of thymocyte differentiation to the leukemic process. TdT peaks I and II were found in fractions A (10 to 23%), B (23 to 26%), and C (26 to 29%) of the thymus of both normal and leukemic C57BL/6 mice, whereas only peak I was found in the same fractions of AKR mice. TdT in bone marrow was found mainly in fraction A in both normal and leukemic mice. The specific activity of TdT in this fraction, which comprises only 1 to 5% of the total bone marrow cell population, was similar to that of the thymus. The cell population of fraction A of the bone marrow was found to increase (10 to 15-fold) in leukemic mice. Only low levels of TdT activity were found in either whole or fractionated bone marrow of athymic NIH Swiss (nu/nu) mice.


Immunologic properties of protein-lipopolysaccharide complexes. I. Antibody response of normal, thymectomized, and nude mice to a lysozyme-lipopolysaccharide complex.

The in vivo antibody response to the lysozyme component of a lysozyme-lipopolysaccharide complex has been investigated in normal, thymectomized and nude mice. The splenic PFC response elicited by the complex in CBA mice is 10- to 20-fold higher than the response elicited by lysozyme admixed with LPS. Both lysozyme-LPS complexes and lysozyme + LPS mixtures prime mice for a subsequent secondary anti-lysozyme response. In contrast, thymectomized mice responded poorly to lysozyme-LPS complexes unless reconstituted with splenic T cells. However, nude mice responded as well as Nu/+ controls to the complex. The PFC response of normal and of nude mice was severely depressed by treatment with anti-lymphocyte serum. These findings suggest that T lymphocytes contribute significantly to the enhanced immune responsiveness associated with LPS administration.


Allotype suppression in rabbits: the requirement for CH3 domain of anti-allotype antibody.

Facb fragments of rabbit anti-allotype antibody were prepared by plasmin digestion and isolated by gel chromatography. The antibody preparation was used in an attempt to induce allotype suppression in newborn rabbits. The Facb fragments were found to be ineffective in inducing the allotype suppression. Administration of Facb fragments caused a "burst" of immunoglobulin synthesis almost immediately after the administration of the antibody. It was concluded that the CH3 domain, which is responsible for the cytophilic activity of the antibody, is essential in induction of allotype suppression.


Inflammatory cells in solid murine neoplasms. IV. Cytolytic T lymphocytes isolated from regressing or progressing Moloney sarcomas.

Highly purified suspensions of intratumoral T lymphocytes, recovered 11 and 13 days after induction of regressing or progressing Moloney sarcomas, were compared in their ability to lyse specifically the MSC cells used for tumor induction. Cytolytic activity, expressed in terms of lytic units/10(6) T cells, was similar for intratumoral T cell suspensions obtained 11 days after induction of either regressing (3.1 +/- 1.3 LU/10(6) T cells) or progressing (4.3 +/- 1.8) neoplasms. By 13 days post-induction, regressing tumors contained T lymphocytes with an increased cytolytic activity (11.1 +/- 4.5) whereas those from progressing tumors were strikingly less able to kill MSC cells (less than or equal to 0.2). This dramatic loss in cytotoxicity could not be attributed to errors associated with the enzymatic disaggregation method, inhibition by copurified endogenous tumor cells, or immunosuppression induced by viral infection. The changes in functional activity of intratumoral T lymphocytes from the two types of sarcoma appeared to be correlated with the stage of neoplasia. In this model system, cytolytic activity of T lymphocytes increased during spontaneous tumor regression whereas losses in cytotoxicity occurred coincident with the onset of inexorable progression.


IgE formation in the rat following infection with Nippostrongylus brasiliensis. III. Soluble factor for the generation of IgE-bearing lymphocytes.

Normal rat bone marrow cells incubated with serum or lymph from Nippostrongylus brasiliensis (Nb)-infected rats showed an increase in the proportion of IgE-bearing cells in culture. This effect was produced in a similar fashion by cell-free supernatants (CFS) from cultures of mesenteric lymph node cells obtained from Nb-infected rats. The action of CFS on bone marrow cells appeared to be specific for the generation of IgE-bearing cells since the proportion of IgM-bearing cells in the culture did not change. The IgE-bearing cells in bone marrow cell cultures consisted of small lymphocytes, blast cells, and mast cells, and the addition of CFS to the cultures predominantly increased the number of IgE-bearing blast cells. CFS was also effective in increasing the proportion of IgE-bearing small lymphocytes in cultures of normal mesenteric lymph node cells. Removal of IgE in CFS by an anti-IgE immunosorbent did not affect the ability of CFS to generate IgE-bearing cells. The factor(s) in CFS responsible for this activity was shown to migrate with serum beta-globulins in zone electrophoresis and to possess a molecular size of between 10(4) and 2 X 10(4) m.w. The ability of CFS to generate IgE-bearing cells was diminished by treatment with the enzymes trypsin and ribonuclease A, but was unaffected by chymotrypsin.


Serum amyloid A (SAA) protein-interaction with itself and serum albumin.

Serum amyloid A (SAA) protein is a 12,000 dalton protein that exists in serum under physiologic conditions as an 85,000 dalton complex and under certain conditions, as a 170,000 dalton component. To study the reason for this finding, the behavior of 125I-SAA was studied in the presence of cold SAA and several serum proteins. SAA caused a shift of some of the radioactivity to the region of albumin. Addition of normal human serum or albumin caused a shift of a significant fraction of the radioactivity to a peak eluting slightly ahead of albumin (80.000 daltons). This interaction could be blocked by the addition of cold SAA. No shift was noted when IgG or Bence Jones proteins were added. Thus, it appears that low molecular SAA protein has a tendency to aggregate with itself and to bind to albumin but not to human IgG or Bence Jones proteins.


Studies of the relationship between adenosine deaminase and immune function.

The relationship between adenosine deaminase deficiency and immunologic responsiveness was studied in mice treated in vivo with deoxycoformycin to produce very low levels of adenosine deaminase activity in tissues. Effects of such treatment on thymocyte response to concanavalin A in vitro and on mixed cultures of splenic cells were determined. Under the conditions used, inhibition of adenosine deaminase by deoxycoformycin had no effect on the viability or responsiveness of either thymocytes or splenic cells.


Expression and function of I region products on immunocompetent cells. II. I region products in T-B interaction.

The anti-Lac B precursor cells from BALB/c (H-2)d mice which survive cytotoxic treatment with anti-Iak and complement will respond to Lac-KLH in culture but require more KLH helper T cells than unselected B cell populations or B cells surviving anti-Ig killing. These findings are not explainable by the classical Poisson assumption of a constant target of T-B ionteraction. We propose a T-B interaction theory with variable Ia target on the B cell surface. The theory quantitatively predicts the observed dose response relationships, and implies that Ia molecules on B cells are cell interaction structures.


Ribonucleoprotein (RNP) soluble nuclear antigen: demonstration of its reaction with serum antibodies by counter-immunoelectrophoresis and further partial characterization.

The soluble ribonucleoprotein nuclear antigen reactive with specific antibodies present in sera from patients with Mixed Connective Tissure disease has alpha 2-beta 1 electrophoretic mobility, thus enabling its reaction with specific serum antibodies to be studied by counter-immunoelectrophoresis. Its molecular weight determined by elution from a calibrated Sephadex G-200 gel column is about 175,000. Its purification has been attempted by successive DEAE cellulose chromatography, Sephadex G-200 gel filtration and Hydroxyapatite chromatography. Polyacrylamide gel electrophoresis of RNP antigen-containing fractions showed persistent heterogeneity which could be due either to inadequate purification or to dissociation of the RNP-antigen during electrophoresis.


Innate resistance and specific immunity in host control of cancer.

A review of the role of immune mechanisms in neoplasia is presented. The role of macrophages in innate resistance, the involvement of T-Lymphocytes and other aspects are discussed. Innate resistance to sporadically occurring malignant cells may be exercised by mononuclear phagocytes. While there is no support for the hypothesis that specific immune processes involving T-lymphocytes determine the incidence of cancer, they influence the biological behavior and natural history of some tumors once they have become clinically evident.


Multi-script modification of the medication list of the POMR.

One solution to the multiplicity of entries required for a complete Problem-Oriented Medical Record is a prescription blank which duplicates itself when overlaid on a medication list of corresponding format by the use of contact-activvated self-printing carbon paper. Used in a large group practice at Fort Sill, such a form yields an exact duplicate of all prescriptions sequentially for validation of prescription information, and accurate, current information on medication in use, while decreasing physician writing time by approximately one half. Screening for drug interactions and for overuse of abuse of medications becomes almost automatic, as the medication list is always before the physician during the writing of all prescriptions.


Studies of the development of frog hemopoietic tissue in vitro. I. Spleen culture assay of an erythropoietic factor in anemic frog blood.

A new in vitro technique has been described for demonstrating the presence of an erythropoietic factor in the circulating blood of frogs. The assay system consisted of MC33 medium, erythropoietically active spleen cells from Rana pipiens, and plasma or serum from frogs made anemic via phenylhydrazine or bleeding. The spleen cells, which remain erythropoietically active for up to nine days, were found to incorporate 59Fe, [3H]thymidine, [3H]uridine, and [3H]leucine at a greater rate in the presence of plasma or serum from anemic versus normal frogs. The hormones triiodothyronine, prolactin, and erythropoietin were not effective in eliciting an hemopoietic response. The data presented suggest that the spleen from that adult frog is a major site of erythroid differentiation and maturation.


Reticular reflex myoclonus: a physiological type of human post-hypoxic myoclonus.

A patient with post-hypoxic  myoclonus, sensitive to therapy with 5-hydroxytryptophan and clonazepam, was subjected to detailed electrophysiological investigation. Brief generalised jerks followed the critical stimulus of muscle stretch. The electroencephalogram showed generalised spikes that were associated with, but not time locked to, the myoclonus. The cranial nerve nuclei were activated upward. Analysis of the findings suggests that the mechanism of the myoclonus is hyperactivity of a reflex mediated in the reticular formation of the medulla oblongata.


Recruitment and suprathreshold frequency modulation of single extraocular muscle fibers in the rabbit.

1. The isometric tension developed by the inferior rectus muscle of the rabbit was modulated by the vestibuloocular reflex (VOR) in unanesthetized rabbits. 2. Single muscle fiber activity was recorded from the inferior rectus muscle during reflex activation. The force at which a muscle fiber was recruited and its suprathreshold frequency-force relationship were studied. 3. The size of individual motor units was measured by averaging the tension which was "time-locked" to the discharge of a single muscle fiber. The average motor unit twitch amplitude was 1.3 mg. 4. The suprathreshold frequency-force function was characterized by an initially steep slope, followed by a less steep slope, until a level of saturation was reached at higher forces. 6. Motor unit size was linearly related to recruitment threshold. Small motor units also had a significantly steeper frequency-force relationship than larger motor units. 7. The relationship between motor unit size and recruitment threshold appears to compensate for changes in the operating point on the length-tension curve of extraocular muscle.


Central depression of carotid baroreceptor pressor response, arterial pressure and heart rate by 5-hydroxytryptophan: influence of supracollicular areas of the brain.

5-Hydroxytryptophan (5-htp) administered into the fourth cerebral ventricle of cats decreased resting arterial blood pressure, preganglionic sympathetic nerve activity and heart rate in both intact brain and midcollicular decerebrate preparations. The increases in sympathetic nerve discharge and blood pressure in response to bilateral carotid occlusion were reduced after 5-HTP administration when the brain was intact but not in midcollicular decerebrate preparations. Resting arterial pressure, heart rate and bilateral carotid occlusion response were not affected when the distribution of 5-HTP was confined to neural structures rostral to the midcollicular level by injection into the third or lateral cerebral ventricle with the cerebral aqueduct cannulated for drainage. Prior intracerebroventricular administration of an L-amino acid decarboxylase inhibitor (Ro 4-4602) prevented the effects of 5-HTP, indicating that depression is mediated via conversion to serotonin. These results suggest that serotenergic stimulation in the caudal brainstem or spinal cord produces depression of sympathetic outflow and decreases arterial blood pressure and heart rate. The bilateral carotid occlusion response is depressed by the brainstem serotonergic mechanisms which require the integrity of neural pathways connecting sub- and supracollicular areas of the brain. The possibility of reciprocal influence by the central serotonergic and adrenergic systems in cardiovascular control is discussed.


Theophylline action on sodium fluxes in frog striated muscle.

The action of theophylline on both sodium efflux and influx was measured using freshly isolated frog sartorius muscles. In normal Ringer's fluid, 2 mM theophylline increased sodium efflux by 35% whereas it decreased sodium influx by about 10%. The percent increase in sodium efflux produced by 2 mM theophylline was not significantly altered in sodium-free, lithium-containing solutions. Strophanthidin prevented the stimulation of sodium efflux by 2 mM theophylline in both normal, sodium-containing Ringer's fluid and sodium-free, lithium-containing solutions. Hence, the major effect of theophylline seems to be stimulation of active sodium transport and the enhanced rate of sodium exit induced by theophylline does not seem to require the presence of external sodium. An interesting and unexplained findings is that 2 mM theophylline, which does not produce a maximal stimulation of sodium efflux, prevents the increased sodium efflux induced by saturating doses of epinephrine.


Regenerative repolarization of the frog ventricular action potential: a time and voltage-dependent phenomenon.

1. The regenerative repolarization process has been examined in frog ventricular myocardium using a single sucrose gap voltage clamp technique. 2. Application of brief (30-150 msec) anodal voltage clamp pulses during the plateau of the action potential revealed a 'threshold' potential region for immediate repolarization. The response to anodal clamp pulses was not all-or-none but was graded. 3. The threshold potential was strongly dependent on the duration of the test voltage clamp pulses and was more negative for shorter clamps. 4. Regenerative repolarization was also observed in the presence of tetrodotoxin. 5. No threshold for immediate repolarization was observed with very short clamps (2-20 msec in duration). Instead the membrane depolarized upon release of each clamp pulse. 6. Theoretical showed that the de- and repolarizations observed after test clamp steps are not due to geometrical properties or inhomogeneous potential distributions. 7. The results suggest that the instantaneous I-V relation of the membrane during the plateau may be linear.


Measurement of transmembrane potential and current in cardiac muscle: a new voltage clamp method.

1. A single sucrose gap voltage clamp technique was developed to correct for artifacts of 'leakage' corrent and extracellular resistance making possible improved measurement of membrane current and membrane potential in cardiac muscle. 2. A fourth compartment termed 'guard gap' was added to the sucrose gap. The guard gap is maintained at the same potential as the Reinger pool, so that no extracellular leakage current can flow into the Ringer pool. Comparison of experimental results with the predictions of an idealized cable model indicates that the guard gap is effective in trapping leakage current. 3. The slow charging of membrane capacitance due to extracellular series resistance was accelerated by applying a 'pre-pulse' of the command potential past the final voltage clamp value. 4. A second technique, termed 'chopped current pulse clamp', was used to compensate for the extracellular resistance throughout the voltage clamp step. The applied current was turned on and off at a frequency of 0-5-2 kHz. The membrane potential sampled during the zero current phase was fed back through the clamp loop. 5. With either of these compensation techniques, the voltage and current traces settle to effectively constant values within 2-4 msec after initiation of a hyperpolarizing voltage clamp step from rest. 6. The membrane conductance measured by the prepulse and chopped current-pulse technique are equal and confirm a higher conductance at rest than during the plateau of the action potential. 7. The 'instantaneous' current-voltage relation of the membrane is linear during the plateau of the frog ventricular action potential.


[Competitive protein-binding radioassay of corticosterone in the plasma of the frog, Rana esculenta L. (author's transl)].

1. Plasma corticosterone levels were measured in the plasma of the edible frog, Rana esculenta, by a competitive protein-binding radioassay method using baboon plasma as CBG source. 2. This technique was sensitive enough to make the assessment of corticosterone levels in 50 microliter plasma samples possible. The assay sensitivity threshold reached 0.5 ng per tube and the corticosterone rate assessment was correct between 0 and 5 ng. The specificity was tested, using 12 different steroids (fig. 2) : baboon CBG had very slight avidity for aldosterone, the second circulating steroid in frog plasma. 3. Using this technique, we have shown that plasma corticosterone underwent seasonal variations. Plasma corticosterone levels, in animals captured in nature during February and June, were 1.51 +/- 0.06 microgram/100 ml (n = 60) and 2.76 +/- 0.14 microgram/100 ml (n = 36), respectively, as appeared in table III. 4. It appeared that the interrenal gland of the frog was not totally dependent on pituitary ACTH, since total hypophysectomy reduced, but did not suppress, corticosterone secretion (table III).


Erythema elevatum diutinum: cutaneous vasculitis, impaired clot lysis, and response to phenformin.

Erythema elevatum diutinum consists of chronic, often painful, predominantly acral skin nodules and plaques, associated with an underlying cutaneous vasculitis. A patient with this disorder is described, who had an elevated sedimentation rate, positive antinuclear factor, impaired clot lysis, and dramatic fibrin deposition in skin vessel walls. A variety of treatments were without benefit in this case as in most others, but phenformin produced marked improvement for periods of 11 and 16 months on two occasions. Protection of the lesions from minor trauma is also important.


Antilymphocyte antibodies in systemic lupus erythematosus: familial clustering of lymphocyte antigens.

Cold reactive lymphocytotoxic sera from patients with systemic lupus erythematosus and their relatives were found to react with lymphocyte antigens that cluster in normal families. These antigens do not correlate with HLA-A or -B antigens in families, suggesting that they are not related to Ir genes. Further work is indicated to determine whether these antigens are controlled by several genes or involve viral products on the cell surface.


Antinuclear antibody: predictive of lymphocyte response in rheumatoid arthritis.

The phytohemagglutinin induced response of lymphocytes was studied in two groups of rheumatoid patients differing only in the presence or absence of antinuclear antibodies (ANA). The response was found to be depressed in 16 ANA positive and normal in 14 ANA negative  patients. Antinuclear antibody screening may serve as a simple method to identify a subgroup of immunodepressed rheumatoid patients who may be potential candidates for immunostimulation therapy.


Cold-reactive lymphocytotoxic antibodies in mixed connective tissue disease.

Eighty-one sera from 18 patients with mixed connective tissue disease (MCTD) and high titers of antibody to ribonucleoprotein (RNP) were investigated for the presence of lymphocytotoxic antibodies. These were found in 59% sera from 14 patients but in only one of 40 normal subjects. Although lymphocytotoxic activity tended to be higher when the disease was active or there was lymphopenia, the correlation was not statistically significant. The lymphocytotoxic antibodies were found to be cold-reactive, and located in the IgM and/or IgG-containing elution fractions from DEAE cellulose columns. IgM-containing fractions tended to be more cytotoxic. Lymphocytotoxic antibodies were partially absorbed out with cerebral cortex but not with ENA-coated sheep red blood cells. Although attention has been focused on the anti-RNP antibodies found in MCTD, other autoantibodies are also present in a high proportion of patients.


Alpha1-antitrypsin deficiency with M-like phenotype.

A patient with a low serum concentration of alpha1-antitrypsin (0-1 g/l) but with an M-like phenotype is described. Her parents and 2 sibs have a PIM phenotype, but all except the father have approximately half-normal levels of alpha1-antitrypsin: The M-like variant apparently cannot be distinguished from M-alpha1-antitrypsin, when it occurs with M in heterozygotes. The proposita has severe airways obstruction and emphysema, and her father has moderate chronic obstructive pulmonary disease. The mother and 2 sibs are healthy.


Haemophilus influenzae type b disease. Incidence in a day-care center.

Haemophilus influenzae type b (HIB) disease was observed during a 14-month period in seven of 48 infants attending a day-care center. Surveillance studies showed that 28 (58%) infants had positive nasopharyngeal cultures for HIB; four infants were colonized with HIB for nine to 12 months. Ampicillin trihydrate prophylaxis failed to reduce the HIB carrier rate. Haemophilus influenzae type b polysaccharide vaccine was administered to 34 of the children. Sera obtained prior to immunization showed detectable antibody in all infants. Only nine (26%) infants had twofold or greater rises in serum HIB antibody titers after vaccination. Antibody response was independent of age, preimmunization antibody concentration, and HIB carrier status. In one infant, HIB meningitis developed four months after she received polysaccharide vaccine. This outbreak emphasizes that HIB is highly contagious in closed populations of young, susceptible infants.


Effect of pretreatment with tricresylphosphates and phenobarbital on the metabolism and toxicity of procaine in rats.

We examined the effects of pretreatment with phenobarbital and tricresylphosphates, TOCP and TCP, on the metabolism and toxicity of procaine in rats. A single administration of procaine at a dose of 250 mg/kg intraperitoneally to adult rats caused convulsion, however, phenobarbital (80 mg/kg intraperitoneally daily, 4 days) pretreatment protected against the toxicity or procaine. In contrast, pretreatment of rats with TOCP (10 mg/kg per os) or TCP (10 mg/kg per os) revealed a higher incidence of toxicity as compared to control rats. Mortality in procaine-treated rats was significantly decreased with phenobarbital-pretreatment and, conversely, increased with TOCP and TCP. Paralysis, convulsion and death were induced at the brain level of procaine of 0.303 +/- 0.025, 0.480 +/- 0.026 and 0.565 +/- 0.018 mumole/g brain wet weight, respectively. Toxic effects of procaine were, therefore, concluded to be due to the accumulation of the drug in the brain.


[Role of the prostaglandin-kinin system of the kidneys in the transport of sodium and water].

The renal content of prostaglandins A, E and F2, was determined by radioimmunoassay in 33 Wistar male rats, following a preliminary purification and separation of these substances by way of chromatography. At the same time, kallikrein excretion in the urine was determined in the same animals by estimating the etherase activity of the enzyme. Several renal function parameters characterizing sodium and water transport were also analyzed. Thirteen animals were receiving Indometacine, 5 mg/kg for 5 days. In the kidneys of those animals who were kept on a routine water-salt regimen certain quantitative relationships were established between prostaglandins of different types and the activity of the renal kallikreinkinin system. Indometacine, when employed in the above dosage, caused synthesis inhibition of prostaglandins A and E, predominantly, and a significant reduction of the kallikrein activity in the urine. These changes in the humoral state of the kidneys under the effect of Indometacine were accompanied by a reduction of diuresis and natriuresis and of the concentration function of the kidneys. The obtained data emphasize the importance of the prostaglandin-kinin system of the kidneys in water and sodium transport.


[Immunostimulating properties of blood serum of rabbits with experimental atherosclerosis].

The effect of serum of rabbits receiving an atherogenic diet on the biosynthesis of antibodies in intact animals was studied. The serum of rabbit kept on atherogenic diets for 6 weeks produced no effect upon the antibody formation when injected to intact rabbits simultanously with antigens. The serum of rabbits receiving cholesterol with their meals for 13 weeks stimulated antibody formation when injected simultaneously with antigens to intact animals. Incubation of the serum of rabbits kept on an atherogenic diet for 13 weeks with the polyvalent proteinase inhibitor Trasylol completely deprived it of its immunostimulating properties.


[Analysis of the relationship between the rate and force of myocardial contractions in dogs, rats and frogs].

Under maximally physiological conditions of arterial blood supply to isolated hearts of dogs, rats and frogs it was found that frequency potentiation of contractility was most distinct in the ventricles of frogs, less distinct in the left ventricle of dogs, and absent in rats. It was demonstrated that in connection with the rhythmic activity the myocardial cells accumulate quantities of calcium proportional to the degree of frequency potentiation. Amounts of calcium were determined that are necessary for a full activation of myocardial contractility proteins, and the amount of calcium entering the myocardial cells of a frog per one systole was calculated. A close approximation of both the values indicates that the activation of a contraction occurs at the expense of the entrance of extracellular calcium during the depolarization of a sarcolemoma.


[Pan-retinal argon laser-photocoagulation in retinopathia diabetica. First results (author's transl)].

The apparition of diabetic retinopathy depends on the duration of the evolution of the diabetes and its control, and its type. The indications for photocoagulation are in progressive retinopathy the existence of macular edema or retinal or prepapillar neovascularisation. The pan-rtinal argon laser photocoagulation is the best technic for treatment. It leads to a global improvement whose results are presented, after 2 years follow-up.


[A new sieve-test for testing colour vision (author's transl)].

From our results we can be sure that the colour test disk is at least as reliable for mass testing for colour blindness as the Ishihara isochromatic colour plates. In practice the test disk has the advantage of constancy of testing conditions and easy and quick procedure. If it is necessary to differentiate between protopia and deuteropia the colour test disk is significantly better Ishihara's colour plates.


Treatment of post-myocardial infarction angina by intra-aortic ballon pumping and emergency revascularization.

Twenty-one patients with postinfarction angina (2 to 15 days after acute myocardial infarction) unresponsive to medical therapy were treated by intra-aortic balloon pumping (IABP). Anginal pain and electrocardiographic (ECG) ST-segment changes were prevented in all patients. Coronary angiograms were obtained during IABP without complication and confirmed severe coronary artery disease. Of the four nonoperated patients, three had reinfarction and two died of cardiogenic shock. Seventeen patients underwent aorta-coronary bypass grafting, associated with aneurysmectomy in two patients and closure of a ventricular septal defect in one. Sixteen patients survived the operation. All survivors are in clinically improved condition and 14 are pain free from 9 to 28 months postoperatively, but three have mild heart failure.


The organization of lymphoid tissue in relation to function.

Organized lymphoid tissue is found in the thymus, spleen, lymph nodes; lining the respiratory and alimentary tracts; and also occurring at sites of chronic inflammation. Apart from the thymus which is involved in the regulation of T-cell function, the other tissues are organized into T-cell and B-cell areas. Lymphocytes in T-cell areas respond by proliferation in cell-mediated immunity and by the production of suppressor cells and helper for antibody formation. B-cell areas are involved in the humoral antibody response. B-cells are segregated into lymph follicles where they form germinal centers and are found at the corticomedullary  junction where they differentiate into plasma cells. The role of lymph follicles in becoming germinal centers is poorly understood, but these areas are known to be the site of antigen trapping in primed animals. The particular function of the spleen as a localized area of lymphoid tissue along the course of the blood vascular system is discussed, particularly with respect to its ability to respond to soluble antigen released from sites of localized antigen deposition such as tumors.


[Apparatus "Stimul-1" foe electric stimulation of muscles].

The apparatus "Stimul-1" has been designed and recommended for batch production, its purpose being broad application in the medical practice of electrical stimulation of the muscles. For stimulation is used sinusoidal a.c. current with frequency of 2 kHz, which produces and effective contraction of the muscles without causing any sensation of pain. The unit is constructed by using up-to-date components, including microminiature logic circuits, operational amplifiers and field-effect transistors.


[Device for correcting elements of human walking by electric stimulation of muscles of the lower extremities].

In recent years electric stimulation of the lower limbs muscles in man while walking, particularly for cases of infantile cerebral paralysis, has found wide application. The device implementing correction of the pace components in walking must be carried directly by man. Therefore, it should be of a minature size, light weight, cheap and contain an autonomic power source. The skeleton diagram and basic technical characteristics of the device's set-up are presented.


Treatment of scleroderma.

A case of scleroderma is presented. Considerable relief of symptoms, healing of ulcers and increased skin and joint mobility occurred. The progressive improvement of the patient's condition was probably due more to potassium para-aminobenzoate (KPAB) than to resurpine.


Diagnosis and follow-up of children referred to a rheumatic disease unit.

Juvenile rheumatoid arthritis (JRA) has become the predominant rheumatic disease of childhood. In a survey of 292 children referred to a rheumatic disease unit over a 5-year period, 94 had JRA and only three had rheumatic fever. At follow-up, of the children with JRA, 70% were found to be in remission with little or no functional disability. Febrile onset of JRA or onset before six years of age were worse prognostic features than pauciarticular or polyarticular onset of occurrence after six years of age. Of 28 children who had either growing pains or psychogenic rheumatism, two were subsequently found to have chondromalacia patellae. None of the other children in this group for whom follow-up information was available had developed organic disease.


Terminal deoxynucleotidyl transferase activity in malignant lymphomas.

To determine the usefulness of terminal deoxynucleotidyl transferase enzyme activity as a biochemical marker in the study of lymphoma, we assayed 50 various malignant lymphomas as well as normal lymphoid tissue for this activity. Neoplastic cells from patients with Hodgkin's disease, Burkitt's tumor, Sézary's syndrome, chronic lymphocytic leukemia, leukemic reticuloendotheliosis and lymphocytic lymphomas (poorly differentiated and intermediate) were all without notable enzyme activity. Large-cell tumors of B-cell type were also negative. One of three large-cell tumors without B-cell or T-cell-surface specificity was positive (1.40 nmol per hour per milligram of DNA). Enzyme activity was consistently present only in lymphoblastic lymphomas (all six cases studied), with a mean activity of 7.80 nmol per hour per milligram of DNA. These six cases had heterogeneous surface immunomarkers. We conclude that terminal deoxynucleotidyl transferase is a biochemical marker that will be useful in the study of lymphoma.


Purification and structural characterisation of human HLA-linked B-cell antigens.

The human B cell-specific alloantigen which is closely linked genetically to HLA contains two non-covalently associated, sialogycoprotein subunits of molecular weight (MW) 29,000 (p29), and 34,000 (p34). Although p29 and p34 have different amino-terminal sequences, their tyrosine peptide maps indicate considerable similarity in other portions of their polypeptide chains. Thus the genes for their proteins may have evolved by duplication of a common ancestral gene. Another lymphocyte cell surface protein of MW 16,000 (p16) has also been characterised. Both p16 and p44 (the heavy chain of HLA-A,B antigens) have been compared with p29 and p34.


Correctable factors contributing to the anemia of dialysis patients.

Twelve out of 60 patients undergoing regular dialysis treatment were found to have an inappropriate degree of anemia. This was not related to duration on dialysis, square meter hours of dialysis or underlying renal disease. Radioactive methods were used to determine blood losses in the dialyzer, lines, at cannulation and from the gastrointestinal tract in the "anemic" patients. Ten of these patients were found to have excessive blood losses and appropriate measures to correct this produced a significant rise in hematocrit in all cases.


[Ventriculography with non-ionic water-soluble contrast medium, Amipaque (metrizamide)-experimental and clinical study (author's transl)].

The excellently low toxicity of a non-ionic watersoluble contrast medium Amipaque (Metrizamide), which is used for ventriculography, was confirmed by animal experiment and clinical application. In the animal experiment, 20 adult mongrel dogs were used and in each of them 1.5-5.0 ml of Amipaque was injected intraventriculary or intracisternally. As a result, we obtained a finding that the Amipaque is cleary safe compared with other watersoluble contrast media, espcially on epileptogenicity, while having an effect on the definition of picture and the nature of cerebrospinal fluid similar to other watersoluble contrast media. Thereafter, 14 ventriculographies were performed for 11 neurosurgical patients by using 4-10 ml of amipaque. Though one patient complained of a light headache after the examination, in no cases could convulsive complication be observed. The experience of this new medium gave us an impression that ventriculography with watersoluble contrast media will take the place of pneumoventriculography.


Thrombocytopenic purpura secondary to quinidine hypersensitivity.

A case of quinidine-induced thrombocytopenic purpura is reported. The patient had been previously sensitized and developed oral bleeding. On repeated ingestion of the drug, he developed classic oral manifestations of the hemorrhagic disease and sought dental treatment. Identification and withdrawal of the drug reversed the clinical and hematologic symptoms.


Bioassay determinations of thymopoietin and thymic hormone levels in human plasma.

Thymopoietin is a thymic hormone that induces differentiation of thymocytes from precursor cells which arise in hemopoietic tissues. This paper describes a sensitive in vitro assay for the induction of Thy 1.2 antigen on null lymphocytes from germ-free athymic (nu/nu) mice. The sensitivity and specificity of the bioassay were increased by adding high concentrations of ubiquitin (a nonspecific inducer) to the induction incubations. The bioassay was sufficiently sensitive to detect thymopoietin at less than 0.25 ng/ml. A dose-response relationship was shown between thymopoietin concentration and the percentage of cells induced to express Thy 1.2 antigen. When normal human plasma was assayed, induction was registered with activity corresponding to thymopoietin at greater than 1 ng/ml in plasma from infants or young adults. Activities in the thymopoietin range of 0.25 ng/ml were registered with plasma from healthy subjects over 50 years of age. Thymectomy was followed by loss of this inductive activity from the plasma. This bioassay permits clinical studies on T (thymus-derived) cell inducers released by the human thymus into the circulation.


[The vascular cerebellopontile angle syndrome].

A cerebellopontine angle tumor cannot be reliably diagnosed from a classical clinicotopographic cerebellopontine angle syndrome. There is also a vascular cerebellopontine angle syndrome which is not too rare an occurrence. In some cases of tumorigenesis, where there is no papilledema and no characteristic increase in total liqour protein, it is not possible to make a clear decision between tumorous growth and vascular syndrome. The extension of the internal auditory meatus cannot be considered to be a symptom clearly indicating the presence of a tumor.


Mixed connective tissue disease: the spectrum of radiographic manifestations.

Mixed connective tissue disease (MCTD) is a serologically distinct entity defined by a ribonuclease-sensitive extractable nuclear antigen. This unusual overlap syndrome has clinical features of scleroderma, systemic lupus erythematosus, polymyositis, and rheumatoid arthritis. In order to define the radiographic changes in MCTD, radiographs of the hands of 17 patients were studied, utilizing a fine-detail technique. Diffuse and periarticular osteopenia were found in 8 and 10 patients, respectively; soft-tissue swelling in 11; erosive changes in 9; joint-space narrowing in 7; tuft resorption and soft-tissue atrophy in 6; and subluxations in 2. In individual cases radiographs may appear normal or exhibit features of scleroderma, systemic lupus erythematosus or rheumatoid arthritis, thereby mirroring the clinical diversity of this entity.


Scintigraphic detection of acute gastrointestinal bleeding.

In induced bleeding experiments on dogs, 99mTc-sulfur colloid was a suitable agent for detecting the bleeding site in the small intestine, providing that the site was distant from the liver and spleen. Bleeding sites were detectable at rates as low as 0.1 ml/min. When induced in the sigmoid or descending colon, the site was demonstrated by scintigraphy with 99mTc-sulfur colloid. Unsatisfactory images were obtained in the esophagus and stomach, however, when 131I-ortho-iodohippurate or 99mTc-DTPA was used.


[Hydroxyapatite rheumatism (multiple tendon calcification disease). I.- Clinical study].

A study was made of 45 patients suffering from hydroxyapatite rheumatism (multiple tendon calcifications disease). There were 36 women and 9 men aged between 15 and 61 years with an average age of 14. The following joints were involved (the first figure refers to clinical affection, that between brackets to radiologically demonstrable calcifications): shoulder 34 (36); neck 14 (15); wrist 18 (11); fingers 19 (17); hip 11 (29); knee 14 (18); ankle 10 (14); foot 5 (6); spinal column 16 (24). In 30 patients the disease manifested itself in the form of acute recurrent migratory arthritis resembling gout. In 8 cases, it developed in the form of acute recurrent migratory arthritis resembling gout. In 8 cases, it developed in the form of acute polyarthritis and in 7 as rheumatoid arthritis without radiological lesions. Thirty-two patients could be followed up. Four of them were cured, 9 showed improvement but still suffered attacks of pain. Eighteen patients were not improved, their pains growing more chronic. Four patients had a family history of multiple tendon calcifications disease.


Humoral function of acute leukaemic blasts.

Leukamic blasts from 8 patients with different forms of acute leukaemia were investigated for their capability to produce colony stimulating factor. A second point of investigation was to detect inhibitory activity from the same blasts. The agar technique in its double layer modification was used with bone marrow from C57 Bl mice as target cell population. No single pattern of colony growth was observed. CSF production was absent or very low, when compared with CSF from normal mononuclear cells. However, blasts from 4 patients disclosed inhibition of colony growth. No certain relationship existed between the cytochemic type of leukaemia and the production of either activator or inhibitor of in vitro colony formation.


B-lumphocyte alloantigens.

Seventy B-cell alloantisera were tested by microcytotoxicity against a panel of B-cell-enriched and T-cell-enriched lymphocytes. Six groups were discerned and have tentatively been designated DIg 1-7 (for Duke immunoglobulin-positive cell groups). These alloantisera were used to type an HLA-A/B recombinant family. Two groups were observed to segregate in this family, DIg 7 with the HLA-B locus and DIg 2 with the HLA-A locus.


Acute bronchodilating effect of transcutaneous nerve stimulation in asthma. A peripheral reflex or psychogenic response.

The acute effect of electric transcutaneous nerve stimulation (TNS) on bronchomotor tone was studied in 20 asthmatics. The stimulation was applied to four classical acupuncture points on the chest and back, and bronchomotor response was determined by measuring peak expiratory flow (PEF). The experiments consisted of an adaptation period, placebo "stimulation", TNS, and an isoprenaline inhalation test, in that order. In 11 patients PEF increased significantly (greater than 15%) after placebo "stimulation"; the mean change in all 20 patients after that period was + 12% (P less than 0.01). TNS, however, did not change PEF significantly in any patient in spite of the fact that marked residual bronchoconstriction was shown in all patients demonstrated by an increase in PEF after inhalation of two isoprenaline puffs at the end of the experiment. The results suggest that the acute bronchodilatation obtainable with TNS is probably psychogenic; no cutaneous-bronchial reflex could be demonstrated. The same kind of psychogenic reaction may also be involved in the bronchodilator response to needle acupuncture in asthma.


T-lymphocyte determination in tuberculosis.

T-lymphocyte determinations in patients with acute untreated tuberculosis showed a significantly higher mean value than determinations in a control group. This finding is in contrast to earlier investigations in non-selected series. The increased mean value was found to be due mainly to increased T-lymphocyte numbers in patients with severe tuberculosis. The amount of T-lymphocytes in chronic alcoholics did not differ significantly from those in other patients. There was no correlation between the number of T cells and the size of reaction in tuberculin skin tests.


Control of a cell surface major glycoprotein by epidermal growth factor.

When the serum concentration of the culture medium is below 0.7 per-cent, 3T3 mouse cells lose most of their large external transformation sensitive (LETS) protein at the cell surface, Subsequent addition of epidermal growth factor results in the reappearance of massive fibrillar LETS protein networks on the surface of conluent 3T3 cells. Thirteen other hormones tested do not have this effect. It appears that epidermal growth factor can control the expression of LETS protein.


Differentiating limb tissue affects neurite growth in spinal cord cultures.

Limb bud mesenchyme enhances and directs the growth of tadpole spinal cord nerve fibers in tissue culture. This effect on elongating neurites may involve alterations in nerve-substratum interactions by the presence of undifferentiated target tissues. The relationship between nerve fibers and their potential innervation sites can explain directed nerve growth to the developing limb.


Induction of suppressor T cells in systemic lupus erythematosus by thymosin and cultured thymic epithelium.

Patients with systemic lupus erythematosus lacked suppressor T cell function. Suppressor cell activity was induced in cells from many of these patients by incubation with thymosin or cultured thymic epithelium. These results suggest that thymic manipulation may be a useful therapeutic modality in this disease.


Ulnar drift and metacarpophalangeal joint subluxation in the rheumatoid hand: review of the pathogenesis.

Ulnar drift and metacarpophalangeal joint subluxation are complicated abnormalities with a wide variety of causes. This paper reviews certain anatomic and mechanical features of the normal hand which predispose toward these abnormalities. In the rheumatoid hand, the major deforming forces include extensor forces, flexor forces, intrinsic forces, and forces from the wrist and carpometacarpal joints. Ulnar drift and metacarpophalangeal joint subluxation result not from any singular cause, but from a combination of all or many of these forces acting upon a joint rendered unstable by rheumatoid synovitis.


A study of the prevalence of severe mental retardation among coloured children in an urban community.

The administrative prevalence of severe mental retardation among Coloured children of school-going age in the Cape Town suburb of Athlone was found to be between 2,64 and 3,36 per 1 000 children. The pattern of additional handicap and the extent to which these children received adequate management was examined. While the level of residential care available was comparable to that provided in Europe, the provision of day training facilities was grossly deficient.


Prognostic significance of portal pressure in patients with bleeding esophageal varices.

Portal pressure was determined in 76 patients during acute bleeding varices, and the degree of portal hypertension was related to the cessation or noncessation of hemorrhage with nonoperative management. A direct relationship between the severity of hemorrhage and the degree of portal hypertension was established. It is suggested that portal pressure be determined as soon as feasible when bleeding varices are suspected and that other causes of hemorrhage be carefully excluded. The obtained data are of great prognostic significance and might be helpful in planning the course of therapy in these individuals.


500 Percutaneous thermocoagulations of the Gasserian ganglion for trigeminal pain.

Five hundred patients with trigeminal pain underwent percutaneous thermocoagulation of the Gasserian ganglion. Of these 416 had classical trigeminal neuralgia, 49 had atypical facial pain and 35 had symptomatic trigeminal neuralgia. The patients ranged in age from 20 to 92 years. These patients have been followed for from eight to 57 months. The beneficial results of this operation and the complications are presented.


Ultrastructural examination of broncho-alveolar lavage for diagnosis of pulmonary histiocytosis X: Preliminary report on 4 cases.

Fibreoptic broncho-alveolar lavage was used in four patients; the diagnosis of histiocytosis X had been established by lung biopsy in three and was suggested on clinical grounds in the remaining patient. Characteristic cells with an ultrastructural cytoplasmic marker (X body) were found in the washes of all four patients. In the patient without biopsy confirmation, the findings in the broncho-aleolar washes supplied the corroborating evidence for the diagnosis. From this preliminary study the technique seems able to provide a diagnosis in pulmonary histiocytosis X without the need for an open lung biopsy.


Inherited bleeding syndromes in Iraq.

This paper presents data on the occurence and pattern of inherited bleeding syndromes (IBS) in Iraq, a hitherto unexplored problem. During the first fourteen months of a prospective on-going study at a major university center, 116 patients from 62 families were diagnosed as having IBS. All patients were referred because of moderate to severe bleeding diatheses. They included 62 haemophiliacs 32 patients with von Willebrand's disease (VWD), 9 with Christmas disease (CD), 6 with afibrinogenemia, 1 with prothrombin deficiency, and 6 were thought to have platelet dysfunction. 32 other bleeders (16 hemophiliacs, 14 VWD, and 2 CD) were also recognized among the pedigrees studied but were not available for full investigations. The clinical and laboratory features of the patients observed in Iraq do not seem to be significantly different from those of patients in Western Europe or North America. Although the absolute incidence and relative distribution of these disorders in the entire population cannot yet be determined, the rate of occurence per segment population is likely to be high, most likely due to the high rate of consanguinity and large number of births per family, phenomena still prevalent in this country.


Cell-mediated immunity to measles virus in subacute sclerosing panencephalitis.

Four patients with subacute sclerosing panencephalitis were investigated for their specific cellular and humoral immunities against measles virus. Lymphocytotoxicity mediated by peripheral blood lymphocytes was evaluated with the colony inhibition test of target cells having measles antigen. The lymphocytes from two patients of subacute sclerosing panencephalitis (SSPE) specifically destroyed the carrier cells; however, no significant lymphocytotoxicity was observed in the other two patients. The result suggests the heterogeneity in cellular immune states in SSPE patients.


[Regeneration of olfactory flagella and restoration of the electroolfactogram following application of triton X-100 to the olfactory mucosa of frogs].

A short-tern (1-1.5 min.) irrigation of the olfactory mucose of the frog Rana temporaria with 0.1-0.15% Triton X-100 in Ringer's solution led to the destroying of olfactory flagella but did not damage the olfactory knob and its flagellar basal bodies. Simultaneously, the generator potential of the olfactory cells-elecroolfactogram (EOG)-disappears. The olfactory cells deprived of fragella were able to produce these organelles. This process begins 2 or 3 hours following theflagellum removal, proceeds in some stages and completes within 2 or 3 days. During the flagellum regeneration the ability of olfactory cells to generate EOG is seen to resotre. The data obtained confirm the presence of receptive sites on flagellar surface.


[Bodily heat resistance and polymorphism of liver esterases of grass frogs].

The determination of organismal heat resistance and qualitative composition of polymorphous liver esterases during heat acclimation (25 degrees) has been made on frogs Rana temporaria. During hybernation the most heat resistant frogs possess the homozygous allele of A2 esterase. Heat acclimation and the summer rise in temperature in nature lead to an increase in heat resistance of frogs and to the disappearance of selective advantage of animals possessing the isoenzyme of the A2A2 esterase. The functional homeostasis of populations can maintain biochemical polymorphism regardless of the selective advantage of individuals possessing one of the homozygous alleles of the isoenzyme.


[Kinetic analysis of mechanisms of Na+-dependent transport of organic acids in the proximal tubules of surviving frog kidney. I. Transport of fluorescein and uranin in a sodium-free environment].

By direct microfluorimetry, the kinetic characteristics of active transport system for organic acid were studied. A removal of sodium from the incubation medium is shown to affect the affinity between a carrier and acids (KS), and the rate of translocation of the transporting complex (which includes a carrier and a substrate) across the plasma membrane. The data obtained are in good accordance with the concept of Na+-dependent transport.


[Studies in heterogeneity of thymus lymphocytotropic low-molecular preparation by gel chromatography on Sephadex G-10].

The low-molecular thymus preparation obtained by dialysis and acetone precipitation is studied by gel chromatography on Sephadex G-10. Gel chromatography was performed on the column equilibrated with 6 M urea at pH 3. The column is calibrated with NADP, ATP, sucrose, glucose and KH2-PO4. The preparation was divided into two fractions with approximate molecular weights of 120-200 and 500-700 daltons.


Absorption tests on cold lymphocytotoxins: preliminary report.

Tests were carried out to absorb cold lymphocytotoxic antibodies on different types of cells. These included lymphocytes and neuraminidase-treated lymphocytes from healthy donors, thymocytes from children undergoing open heart surgery, fetal thymocytes, human brain and cultured lymphocytes. The results showed these antibodies to be absorbed on some types of cells and eluted from others. The best absorption was obtained with fetal thymocytes and brain tissue.


Clinical and immunological studies on healthy blood donors hepatitis B antibody carriers.

Ten healthy blood donors persistently seropositive for anti-HBs and without a history of clinically overt viral hepatitis were studied. While physical examination and biochemical liver function tests exhibited normal values in all cases, immunologic studies revealed coexistence of a long-term anti-HBs carrier state with the presence of cell-mediated immunity to HBV antigens and autoantibodies in some. These results suggest a complex immunologic phenomenon underlying the development of the anti-HBs carrier state.


[Effect of thyroid and adrenal hormones on the course of hypervitaminosis A and D].

Tests staged on normal and hypophysectomized rats demonstrated thyroxin to potentiate the general toxic effect of ergocalciferol, with final death of the animals. At the same time, the blood calcium content in animals receiving thyroxin decreases under the effect of the latter. Hydrocortisone, while producing no effect on the high calcium content in the blood of the animals receiving ergocalciferol, attenuates the general toxic action of the latter. These data point to the possibility of dissociating the general toxic action of ergocalciferol and its influence on the blood calcium level, which disproves the existing notion on the correlation between general toxic action of ergocalciferol and hypercalcemia produced by it. Thyroxin and hydrocortisone do not have any effect on the nature of the action exerted by high doses of vitamin A.


[Pararheumatic diseases in leukoses].

Pararheumatic complaints may be the leading clinical symptom in the individual case also in leucoses and may lead to diagnostic errors. They are caused by leucotic infiltrates in juxta-articular bone segments, sporadically also by blast infiltrates of the synovial membrane, by secondary osteoporoses or osteoscleroses and by articular haemorrhages. In altogether 254 patients with leucosis there were rheumatoid symptoms in 21% of the cases with undifferentiated cell leucoses, in 37% of the cases with chronic myelosis, and in 12% of the cases with chronic lymphadenosis. Diagnostic errors are deplorable above all in the undifferentiated cell leucosis, as every temporary retardation of the beginning of the therapy furthermore deteriorated the prognosis of the disease.


[Comparative analysis of conservative and surgical treatment of the imminent myocardial infarct].

It is reported on 108 patients with the symptoms of the impending myocardial infarction, of whom 80 patients were treated conservatively. 51 patients developed a fresh definitive myocardial infarction. 28 patients were surgically treated, 5 of them died. Therefore, in patients with instable angina pectoris the possibility of an early coronary-surgical intervention should be taken into consideration to prevent the development of a definitive myocardial infarction.


Electrophysiologic evaluation of intravenous bunaphtine in man.

The acute electrophysiologic effects of intravenous Bunaphtine 1,5 mg/kg body weight, a new antiarrhythmic drug, were studied in 19 subjects with estimated normal impulse formation and conduction. Significant effects were sinus bradycardia, prolongation of atrial refractory periods, depression of intranodal and infranodal conduction and prolongation of His-Purkinje system refractory periods. These properties are compared with those of amiodarone and quinidine and form the basis for a correct use of Bunaphtine in the management of arrhythmias.


Haemodynamic effects of physical training in essential hypertension.

The haemodynamic effects of four weeks of daily intensive training on bicycle ergometer were studied in 10 men with essential hypertension of grade II (WHO). Three weeks before training all medication was replaced by placebo. Five days before onset of training all patients underwent a haemodynamic examination using floating catheter and direct brachial arterial pressure at rest and during effort. The same examination was repeated within five days after the completion of the training. Resting measurements did not demonstrate any effect of the training on systemic pressure or central haemodynamics. At the given load, however, a significant decrease for the pressor response occurred, i.e. lowering of systolic, mean and diastolic arterial pressure. Peripheral vascular resistance was not affected. Cardiac output (Fick) decreased insignificantly both at rest and during effort after training. Heart rate decreased significantly only during exercise. The training lowered significantly both tension time index and left ventricular stroke work index. No adverse clinical or haemodynamic effects of short intensive training were detected in hypertensive patients. There was no evidence of changes in pulmonary artery diastolic pressure considered as an indicator of the left ventricular filling pressure. The heart volume remained unchanged after training.


Rocking motion of the right cardiac cavities in Ebstein's anomaly. A specific cineangiographic sign.

In 7 cases of Ebstein's anomaly the right cineangiogram disclosed a big right atrium, the tricuspid valve positioned to the left of the spine and tricuspid regurgitation. The right atrial appendage was nearing the outflow tract of the right ventricle and the pulmonary artery so as the normal U appearance of the right aniograms was abolished. In addition to these signs a very characteristics and almost pathognomonic rocking motion of the radiopaque material, moving from the right atrium towards the right ventricle during ventricular diastole and backwards to the atrium during the next ventricular systole was observed. This sequence of motion gives the impression of a rocking hammock or pendulum.


First-degree trifascicular block unmasked by sinus arrhythmias. Report of a case studied with intracardiac electrocardiography.

A case is presented in which first-degree block in all three fascicles of the intraventricular conduction system results in a QRS complex with no specific features of fascicular block. During spontaneous sinus arrhythmia the typical features of RBBB and LAH appear at the longest sinus cycles. This is associated with shortened P-R and H-Q intervals. During shorter sinus cycles, near equalization of delay in each fascicle is associated with delay in His-Purkinje conduction but loss of the typical features of bifascicular block as the ventricular myocardium becomes activated more synchronously. Documentation of the changing patterns of ventricular activation is provided by His bundle electrocardiography.


Ventricular rhythm obscuring the diagnosis of ostium primum atrial septum defect.

A 13 year old boy with an ostium primum atrial septal defect associated with alternating periods of sinus rhythm and ventricular rhythm is presented. Absence of auscultatory and phonocardiographic signs of an atrial septal defect made it impossible to diagnose the defect correctly during periods of ventricular rhythm.


The influence of prolonged lidoflazine (R 7904) treatment on resting ECG, heart rate and blood pressure. A retrospective study.

Resting ECGs of 172 patients (33-77 years) with anginal complaints, who had been treated for several months with lidoflazine 120-360 mg/day, together with all available data on blood pressure and heart rate were collected and analysed over a period of at least one year after the start of lidoflazine treatment. Both systolic and diastolic blood pressure decreased significantly from the sixth month onwards; heart rate and P-duration decreased gradually, whereas (TI-TIII) and (TV6-TV1) increased significantly. Data also showed that prolonged treatment with lidoflazine favourably influences typical ischaemia-related ECG aberrations in angina pectoris patients.


[Functional relationships between the horizontal and vertical anterior semicircular canals in the labyrinth of the frog (Rana esculenta L.)].

We have studied the vestibular postrotatory reactions (reactions elicited by the stimulation of the horizontal semicircular canals) in the frog blinded by section of optic nerves, before and after section of the ampullary nerves of the vertical anterior semicircular canals (VAC). 90 frogs have been studied. In 30 frogs the ampullary nerves of the two VAC have been cut; in 60 animals either the ampullary nerve of the right VAC or of the left VAC has been cut. Both after section of the ampullary nerves of the two VAC and after section of the ampullary nerve of one VAC, the postrotatory reactions were decreased in about the half of the animals. The decrease of the postrotatory reactions is not due to a lesion of the ampullary nerves of the horizontal semicircular canals and it may be explained by the existence of functional connections between the VAC and the horizontal canal.


Permanent effects of low frequency vibration on the vestibular system.

Among 49 male workers, mean age 30 years, who had been working in conditions of extreme noise and vibration for between 6 months and 10 years vestibular disturbances could be shown (in the form of spontaneous nystagmus, lowered caloric excitability, or pathology in rotatory tests) in as high as 44.9%. The lesions were believed to have arisen in the peripheral vestibular organ as a consequence of the low frequency vibration.


Occlusion of the internal carotid artery complicating Haemophilus influenzae meningitis.

We report a patient with occlusion of the internal carotid artery complicating Haemophilus influenzae meningitis. The etiology of this complication is discussed, along with its role in the acute seizures of meningitis, and in the chronic neurological residua of this infection.


Saphenous vein bypass graft to left main coronary artery.

The first reported aorto-left main coronary artery saphenous vein bypass for an aberrant left main coronary artery arising from the anterior sinus of Valsalva is presented. Late follow-up revealed a normal stress test, and cardiac catheterization revealed the left system to be entirely supplied by the graft.


Electron-microscopic analysis of iris vessels in two cases of uveitis.

Electron-microscopic analysis of iris biopsy material was carried out paying particular attention to vessels and infiltrating cells. Characteristic changes of vessels and cells were found in two cases. One showed abundant lymphodiapedesis, perivascular infiltration, and vessels appearing morphologically normal. The other showed diffuse infiltration of cells and numerous fenestrated newly formed vessels. In the latter, three different types of opening in the endothelium were observed: (1) separation of intercellular junctions; (2) small pores or defects in the endothelium, and (3) large holes or defects in the endothelium. Cell leakage from normal and newly formed vessels was considered. We concluded that lymphocytes may migrate through the cytoplasm within membrane-bounded vesicles in normal vessels, whereas in newly formed fenestrated vessels cells, including small lymphocytes, may pass through three different types of opening in the endothelium.


[Phenylalanine-influenced retinal changes in the newborn rat (author's transl)].

Subject of the present study was the retina of rats following intravenous application of L-phenylalanin. The 19 newborn rats received 0.9 mg/g of the substance twice daily from the first to the seventh postnatal day. Depending on the survival time, alterations of ganglion cells, neuropil, and capillaries were found. Pyknotic and necrotic cells in the bipolar and in the ganglion layer occurred. Animals that were treated for a period of five days developed a marked increase of free ribosomes and round particles with a granular matrix of the cytoplasma but without membranes. Also suggesting damage is the increase of the glycogen in the bipolar and the inner granular layer as well as in the nerve cell extensions adjacent to the capillaries. An additional finding is the swelling of processes of the glia and of neuronal cells in the vicinity of the retina vessels. Since newborn rats do not have the blood-brain carrier of adult animals, toxic damage of the cell membranes with intracellular liquid accumulation can be concluded. Our findings suggest that L-phenylalanin can damage the nerve cell substantially and that alterations of the white matter so far described are not the sole basis of phenylketonuria.


[Ear to retina time and ophthalmodynamometry after ligation of the common carotid artery in rabbits (author's transl)].

Unilateral ligation of the common carotid artery was performed in rabbits. Before ligation, immediately thereafter, and 6 weeks later the ophthalmic artery pressure was determined and at the same time a synchronous measurement of the ear to retina time was done on both sides. The results were statistically analyzed (Tables 1-4). Ligation of the right common carotid artery resulted in a highly significant difference in systolic ophthalmic artery pressure between the two eyes of 16.4 mm Hg, and in diastolic pressure one of 13.0 mm Hg. After ligation of the left similar pressure differences of (systolic) 17.8 mm Hg and (diastolic) 15.2 mm Hg were shown. During the following 6 weeks these differences decreased considerably, to 41.5% and 29.2% after ligation on the right and to 33.5% and 36.6% after ligation on the left. The ear to retina time was markedly prolonged on the side of the ligation. This resulted in a highly significant side difference of 0.42 s immediately after ligation on the right common carotid artery and 0.4 s immediately after ligation on the left side. After 6 weeks these differences were only slightly reduced, to 80% and 72.7% respectively. These animal experiments demonstrate clearly that an acute occlusion of one common carotid artery in rabbits can easily be diagnosed by ophthalmodynamometry as well as by synchronous measurement of the ear to retina time. In chronic occlusions determination of the ear to retina time is superior to pressure measurement. This is of particular interest since in these experiments an ophthalmodynamometric method was used that is much superior to the clinical method of ophthalmodynamometry.


Lens-induced uveitis: further immunological studies in an experimental model.

Inbred rats have been studied to determine under what circumstances sensitization will or will not induce uveitis. After 50 days of biomicroscopic follow-up and histologic evaluation of 119 eyes the following was found in black hooded CAP-rats (RtH-1c) presensitized to eye, liver or kidney (guinea pig): 1. Alterations only following additional damage to their own tissue by lens discission plus iridotomy 2. As the case of lens-induced uveitis in humans, alterations after the disappearance of traumatization reaction in the form of protein-rich exudate clinically and an accumulation of round cells in the anterior uvea, surrounding the lens and retinal vessels histologically 3. Dependence of these alterations on sensitization by xenogenic tissue 4. Dependence of the alterations on the animal strain, i.e. absence in albino LEW (RtH-1(1)).


Vitrophage in management of congenital cataracts.

We have used the vitrophage for combined lensectomy and vitrectomy in six eyes with congenital cataracts. No intraoperative complications were encountered. One week after operation four of the six eyes had clear corneas, and all eyes showed a bright red reflex. With follow-up ranging from 18 to 21 months all eyes had clear corneas and a view of the posterior pole consistent with 20/20 vision.


The relation of serum immunoglobulin A and delayed hypersensitivity skin tests to serum immunoglobulin E levels.

Serum IgA and IgE levels were obtained in 706 patients, 294 of whom were also tested for cutaneous delayed hypersensitivity. The results do not support the concept that a deficiency of serum IgA or of T lymphocyte function underlies the elevated serum IgE levels observed in a majority of allergic patients.


Management of severe respiratory insufficiency due to Pneumocystis carinii pneumonitis in immunosuppressed hosts: the role of continuous negative-pressure ventilation.

Continuous negative-pressure therapy was used to assist ventilation in 19 spontaneously breathing patients, 6 months to 17 years of age, who developed progressive respiratory insufficiency (arterial PO2 less than 70 mm Hg despite a fraction of inspired O2 larger than or equal to 50 per cent) due to Pneumocystis carinii pneumonitis. Within 1 hour of therapy, arterial PO2 increased from a mean +/- SE of 61.9 +/- 3.7 to 75.4 +/- 7.0 mm Hg (P less than 0.05) and, by 6 hours, to 79.9 +/- 4.7 mm Hg (P less than 0.005). In the 14 survivors, these improvements were sustained and, within 24 hours, permitted a decrease in inspired O2 concentration from a mean +/- SE of 50.4 +/- 1.2 per cent to 40.1 +/- 1.6 per cent (P less than 0.005). By contrast, in nonsurvivors, O2 requirements could not be decreased significantly despite increases in negative pressure. Improvements in arterial oxygenation were associated with decreases in alveolar-arterial PO2 differences in all patients; however, significant decreases occurred only with pressures of -8 to -12 cm H2O. Higher negative pressures were ineffective and usually produced pulmonary air leak. Since the introduction of continuous negative-pressure therapy as a means of assisting ventilation in management of progressive respiratory insufficiency, the over-all survival rate among patients with Pneumocystis carinii pneumonitis at this institution has increased from 69 to 89 per cent.


alpha1-Antitrypsin deficiency in clinic patients.

Five hundred patients undergoing complete medical examination, and 225 consecutive patients with abnormal pulmonary function tests were studied for alpha1-antitrypsin deficiency. Within the first group, respiratory disease was diagnosed significantly more often in patients with a variant Pi phenotype (MS, MZ, FF) than in the patients with the most common phenotype, MM. Furthermore, the frequency of heterozygosity (MS or MZ) was greater in the patients who had respiratory disease. When the first and second groups were compared, the prevalence of the variant phenotypes was not statistically different.


Mycobacterium marinum infections treated with tetracycline.

Five cases of Mycobacterium marinum skin infections were successfully treated with 2 gm of tetracycline hydrochloride daily for periods from four to 12 weeks. In each case, the isolated M marinum was sensitive in vitro to tetracycline at levels from 25 to 50 microgram/ml. Tetracycline is recommended as treatment for extensive or sporotrichoid M marinum infections.


Mallory-Weiss syndrome. A changing clinical picture.

A retrospective study of 18 episodes of upper gastrointestinal (UGI) bleeding secondary to Mallory-Weiss syndrome occuring in 16 patients is presented. Reported cases published since 1969 have been summarized and compared with earlier collected series. It is evident that the clinical spectrum, prognosis, and opinion regarding etiology and treatment of the syndrome have changed in the last decade. Increased awareness of gastroesophageal lacerations secondary to emesis as well as other causes of significantly increased intraesophagogastric pressures, and widespread utilization of fiberoptic endoscopy have resulted in identification of Mallory-Weiss syndrome with increasing frequency. Less severe lacerations which are healing with medical therapy are being recognized. It is recommended that endoscopy by performed in all cases of UGI hemorrhage and that patients with Mallory-Weiss syndrome be managed medically unless hemorrhage is massive or persistent since nearly three of four patients can be successfully treated without operation.


Surgery for post-myocardial infarct ventricular septal defect.

Forty-three patients (mean age 62 +/- 1 years) were treated for ventricular septal defect (VSD) secondary to myocardial infarction. Whenever possible, operation was postponed until six weeks post-onset chest pain. However, hemodynamic instability, evidenced by cardiogenic shock, refractory pulmonary edema, or a rising blood urea nitrogen (BUN) forced operation in 21 patients within 21 days post-infarct (Group I). In seven patients operation was performed three to six weeks post-infarct (Group II). In only eight patients could operation be delayed beyond six weeks post-infarct (Group III). Clinical deterioration, once begun, progressed rapidly, and could be reversed only temporarily by intra-aortic balloon pumping, used in 26 patients for safe conduct of cardiac catheterization and for peri-operative hemodynamic support. Hospital survival was achieved in 24 of the 36 operated patients (66%). In Group I patients, ten of 21 survived. In Group II, six of seven survived. In Group III, eight of eight patients survived. There have been five late deaths with a mean follow-up of 41 months in survivors. Improved survival has been achieved recently by the greater use of prosthetic material to replace necrotic muscle and by a transinfarct incision regardless of infarct location. Operative mortality before 1973 was 47%; mortality after 1973 was only 18%, with a concomitant reduction of mortality (30%) even in Group I patients.


Control of bleeding varices by vasopressin: a prospective randomized study.

From July 1975 to November 1976 25 patients with bleeding esophagogastric varices documented by endoscopy who failed to respond to conservative medical treatment were transferred to the Surgical Service. These patients, who were mainly Child's Class "C" alcoholic cirrhotic patients, were treated with vasopressin infused continuously using a standardized dose into either a peripheral vein or the superior mesenteric artery (SMA) according to a predetermined randomization. No significant difference in efficacy for control of bleeding (average rate = 56%) related to route of administration was found. Because catheter-related complications in the SMA group were significantly greater, we concluded that the method of choice in vasopressin treatment of esophagogastric variceal bleeding is a continuous infusion by way of a peripheral vein.


Obtaining, evaluation and clinical application of antileukemic antilymphocyte globulin (ALLG) in the treatment of chronic lymphatic leukemia.

Antileukemic antilymphocyte globulin (ALLG) was obtained by immunizing horses with peripheral blood lymphocytes from patients suffering from chronic lymphatic leukemia. After absorbing the serum with erythrocytes, globulins were precipitated from the serum with ammonium sulfate. ALLG preparations were sterile, nontoxic and nonpyrogenic and contained no antibodies against basement membranes or antierythrocytic or antiplatelet antibodies. Nine patients with chronic lymphatic leukemia were treated with the globulin. Methods for selecting patients for treatment with ALLG and for controlled therapy were elaborated. Clinical and hematologic observation in the patients were reported. The high therapeutic efficacy of ALLG with high cytotoxic titer was emphasized. Beneficial hematologic and therapeutic effects were obtained in six patients. Attention was drawn to the efficiency of the combined therapy with ALLG, cytostatics and adrenal steroids.


The effect of cordycepin on the multiplication of Semliki Forest virus and on polyadenylation of viral RNA.

Cordycepin (3'-deoxyadenosine), at a concentration of 20 microgram/ml, has a marked effect on Semliki Forest virus multiplication. The appearance of plaque forming units is delayed by about 2 hours and the yield greatly reduced. The incorporation of [3H] uridine into intracellular viral RNAs reaches less than 50 per cent of controls. However, no specific effect on poly (A) synthesis could be detected. The binding efficiency of viral RNAs on nitrocellulose membranes and poly (U) sepharose is not affected by cordycepin. The average poly (A) length of total intracellular viral RNA was calculated on the basis of the ratio of the radioactivity of adenosine-monophosphate: adenosine and found to be about 35 nucleotides in treated and untreated cells.


Coordination of the head and eyes in pursuit of predictable and random target motion.

Subjects were required to use their head and eyes in pursuit of visual targets which moved randomly or sinusoidally in the horizontal plane. All subjects disliked moving their heads to pursue the random motion, apparently because the motion broke fixation which resulted in a predominance of the vestibulo-ocular compensatory reflex over the smooth pursuit reflex. As a consequence gaze (head plus eye movement) was at times in the opposite direction to the motion of the target. In steady state pursuit of sinusoidal targets, eye movement consisted of a combination of pursuit and vestibulo-ocular reflex eye movements. At frequencies below 0.8 HZ, the vestibular reflex was used at times of minimum target velocity to stabilize fixation whereas during maximum target velocity the head movement was slowed and the smooth pursuit reflex predominated. At 1 HZ and over, there was a failure to suppress the compensatory vestibulo-ocular reflex; however, the saccades of vestibular nystagmus were used to "catch up" the target. There was a preference not to use the head in predictable pursuit.


[Emergency colectomy in ulcerative colitis (author's transl)].

During the last 12 years 7 patients with ulcerative colitis were treated because of an acute complication consisting in 2 cases of colonic perforation, 3 cases of toxic megacolon (two of them perforated) and 2 cases of massive enterorragia. In all patients an emergency total colectomy was performed resulting a mortality of 3 cases, two of which had required the removal in a second time of the rectal stump. In 3 or 4 recovered patients we performed in a period of 7-15 months an ileo-proctostomy once confirmed the healing of the ulcerative lesions in the residual rectum. The problems concerning the indications and surgical procedures involved in such cases are discussed on the base of the personal experience, with particular consideration on advantages and limits of preserving a rectal stump. The authors agree on an eclectic behavior considering each case on the base of pathological findings, the age and the general and psychic conditions of the single patient.


Treatment of advanced bronchogenic carcinoma with adriamycin, 5-fluorouracil and methotrexate.

The combination of adriamycin, 5-fluorouracil and methotrexate with folinic acid reversal was used to treat patients with advanced bronchogenic carcinoma. Twenty-one of 30 patients showed an objective response. This combination appears to produce useful remissions in patients with non-squamous lung cancer.


The effect of androstanes on granulopoiesis in vitro and in vivo.

Bone marrow culture in a patient with aplastic anaemia responding to anabolic steroid (methandienone) therapy, showed an unusually high degree of growth in unstimulated cultures. Growth in unstimulated cultures is due to factors with colony stimulating activity (CSA) released by monocyte macrophages in the bone marrow sample. These cells, which can be identified by staining for non-specific esterase activity, were not increased in this patient's marrow, implying either increased production of colony stimulating factors or increased sensitivity to these factors. Addition of methandienone or testosterone to feeder-layers containing normal peripheral blood leucocytes increased their stimulatory activity. Addition of these drugs to feeder-layers of CSF-containing conditioned medium did not have this effect, implying that androstanes cause increased production of colony stimulating factors rather than increased sensitivity to them. Lack of response to androstane therapy may be related to lack of response by bone marrow monocyte macrophages or to the inability of granulopoietic cells to respond to the increased CSF production induced by androstane therapy. A means of predicting lack of response is proposed.


Control of light-activated phosphorylation in frog photoreceptor membranes.

In this paper, we examine some factors which regulate the efficiency of light in activating rhodopsin phosphorylation. We have measured phosphate incorporation after illumination in suspensions of bullfrog rod outer segments incubated with [gamma-32P]ATP. We observed that delaying ATP addition after illumination causes maximum phosphate incorporation to decrease 80% within 2 h. This decay occurs in urea-treated, extracted rod outer segment membranes. The decay of the light effect is not influenced by regeneration of opsin to rhodopsin or the presence of long-lived photoproducts. However, regeneration of opsin increases the amount of phosphorylation initiated by a second exposure to light. Further phosphorylation can also occur after phosphate groups have been removed from the membranes by dephosphorylation. Finally, we have confirmed our earlier observation that small amounts of light (bleaching less than 5% of the rhodopsin present) are more effective, by tenfold, in initiating phosphorylation than are larger amounts.


Oxygen consumption by frog skin and its isolated epithelial layers as a function of their sodium-transporting activity.

The metabolic cost (in terms of oxygen consumption) of transcellular sodium transport was assessed on ventral frog skin and its isolated epithelial layers, by measuring the decrease in oxygen consumption by the tissue upon transient withdrawal of sodium from the outside solution. The same number of sodium ions was transported per molecule oxygen consumed whole skin (17.4 +/- 2.3) and its isolated epithelium (17.3 +/- 2.4). The metabolic cost of sodium transport could not be estimated properly when this process was blocked by amiloride or ouabain, as these drugs were found to bring about an increase in oxygen consumpton by the tissue when no sodium was available for transport.


Magnetic field effects on radical pair intermediates in bacterial photosynthesis.

We have investigated the effects of magnetic fields on the formation and decay of excited states in the photochemical reaction centers of Rhodopseudomonae sphaeroides. In chemically reduced reaction centers, a magnetic field decreases the fraction of the transient state PF that decays by way of the bacteriochlorophyll triplet state PR. At room temperature, a 2-kG field decreases the quantum yield of Pr by about 40%. In carotenoid-containing reaction centers, the yield of the carotenoid triplet state which forms via PR is reduced similarly. The effect of the field depends monotonically on field-strength, saturating at about 1 kG. The effect decreases at lower temperatures, when the yield of PR is higher. Magnetic fields do not significantly affect the formation of the triplet state of bacteriochlorophyll in vitro, the photooxidation of P870 in reaction centers at moderate redox potential, or the decay kinetics of states PF and PR. The effect of magnetic fields support in view that state PF is a radical pair which is born in a singlet state but undergoes a rapid transformation into a mixture of singlet and triplet states. A simple kinetic model can account for the effects of the field and relate them to the temperature dependence of the yield of PR.


[Mechanism of the formation of single-stranded DNA breaks under the effect of prednisolone on rat liver thymocytes].

Rat liver thymocytes were incubated in vitro with prednisolon, and molecular weight of single-stranded DNA was estimated in alkaline lysates of nuclei by viscosity methods. The number of single-stranded breaks was estimated, which originate in DNA after 3 hours of incubation with prednisolon at a concentration of 3-10(-9) M--3-10(-4) M. Maximal hormone effect was produced within 30 min., and it remained constant for the rest 3 hours of the incubation. Cycloheximide prevented hormone-induced DNA depolymerization, and actinomycin D only slightly inhibited the formation of single-stranded DNA breaks, originated after 30 min. incubation of thymocytes with prednisolon, were repaired after their washing and reincubation in the fresh medium for 1 hour at 37 degrees C. The washing of thymocytes and their reincubation for 3 hours resulted in the decrease of the molecular weight of single-stranded DNA. Possible mechanism of the formation of single-stranded DNA breaks in prednisolon-induced thymocytes is discussed.


In vitro synthesis of alpha-1-antitrypsin in long term monolayer human liver cell cultures.

Explants for long term monolayer liver cell cultures were taken from individuals having PiM or PiZ phenotypes. Radioactive labelling, using I125 and an original method, permitted the quantitative measurement of AAT in vitro and more important, allowed Pi phenotype determination.


Interaction of colony stimulating factor (CSF) from different sources with sepharose-concanavalin A.

Preparations from various sources (human urines, mouse placenta and pregnant uterus extract, and fibroblast conditioned medium) were examined comparatively with affinity chromatography on Sepharose-Concanavalin A for the presence of Colony Stimulating Factor (CSF). The preparations from all sources constantly revealed two protein peaks: the proteins of the first peak, without Concanavalin A affinity, contained CSF in the material from pregnant uterus and fibroblast conditioned medium, while human urine preparation was devoid of CSF: the inhibitor of CFUc growth, detected and titrated in this peak, probably does not explain the lack of CFUc growth. The proteins from the second peak, specifically eluted with alpha-methyl D-glucopyranoside revealed CSF in all the examined preparations.


[Analgesia following electrostimulation of midbrain nuclei of rats with a pain syndrome of spinal origin].

The effect of electrostimulation of the mesencephalic grey matter and of the dorsal nucleus raphe on physiological pain produced by nociceptive stimulation (compression of the tail or the skin on the limb by a clamp) and on pathological pain (the pain syndrome of spinal origin) were studied in experiments on albino rats. Pathological pain was induced by creating a generator of pathologically enhanced excitation in the dorsal horn of the spinal cord by local disturbance of the inhibitory mechanisms with the aid of tetanus toxin. It was shown that electrostimulation of the indicated areas abolished both physiological and pathological pain. A conclusion was drawn that analgesia produced by electrostimulation of certain structure of the brain was connected not only with augmentation of the descending inhibition in the spinal cord as in the case of physiological pain caused by peripheral nociceptive stimulation (as shown by several authors), but also with the block of excitation at the supraspinal level. This mechanism should play a decisive role in analgesia realization in the pain syndrome of central origin, both under experimental and natural conditions.


[Changes in the concentration of catecholamines in the organs of animals with experimental myocardial infarcts under the influence of malaben].

The content of adrenaline and noradrenaline in the tissues of the heart, adrenal glands, spleen and brain of rats was studied in experimental myocardial infarction. A significant decrease in the catecholamine levels was revealed in the tissues. Malaben promoted normalization of the catecholamine tissue content in myocardial infarction. It is suggested that the said effect of malaben is due to its antihistaminic properties.


[Effect of cortisone-resistant thymocytes on endogenous colony formation in inbred mice].

Endogenous colonies in the spleen of sublethally irradiated (CBA X C57BL/6) E1 hybrid mice were recorded after the injection of thymocytes and the lymph node cells from the hydrocortisone-treated and intact CBA mice. Cortisone-resistant thymocytes failed to suppress the endogenous colony formation, whereas the lymph node cells produced a distinct suppressive effect on the endogenous colonies. After the injection of cortisone-resistant thymocytes the number of colonies in the spleen of individual recipients was double that in control irradiated hybrids.