Properties of antisera against lymphocytes of nude mice. The activity of rabbit antisera against nu/nu BALB/c lymphocytes was estimated in vivo and in vitro. It was found that anti-lymphocyte serum (ALS) against nu/nu lymph node cells suppressed the alloantigen reaction and the spontaneous rosette-forming cell (sRFC) or plaque-forming cell (PFC) formation for T-dependent (sheep red blood cells) and T-independent (lipopolysaccharide) antigens. ALS against nu/nu spleen cells affected only the sRFC and PFC for T-independent antigen. The former serum exhibited a high cytotoxicity for the suspensions enriched or depleted in B cells, while the latter was more cytotoxic for the suspension enriched in B cells. This may indicate that ALS anti-nu/nu spleen cells is specific for B lymphocytes, and ALS anti nu/nu lymph node cells is directed not only to B cells but also to a subpopulation of T lymphocytes. It may suggest the existence of a subpopulation of T lymphocytes in nu/nu lymph node cells.


Requirement for antigen in lipopolysaccharide-dependent induction of B cells. The magnitude of the IgM response to a variety of antigens, induced on the in vivo administration of lipopolysaccharide (LPS) to mice, is approximately proportional to the magnitude of the background response observed in untreated animals. This striking correlation suggests that the administration of LPS alone cannot in general induce a specific response in the absence of a background response. Such is the case for the antigen rat erythrocytes against which no LPS-dependent or background response is found. The response to a marginally immunogenic dose of rat erythrocytes, however, can be considerably enhanced by the administration of LPS. These observations are expected on the hypothesis that both background and LPS-induced responses are due to ongoing antigen-dependent stimulation in normal mice. This hypothesis is further supported by evidence suggesting that the LPS-dependent anti-sheep erythrocyte response is due, at least in part, to a particular antigen present on degraded mouse erythrocytes.


Inhibition of "wet shakes" during morphine abstinence by an antagonist of opiate analgesia. An antagonist of morphine analgesia, N-cyclopropylmethylnorazidomorphine (CAM) inhibited the"wet shakes" appearing during spontaneous or nalorphine-precipitated morphine abstinence. CAM inhibited the pinna reflex more strongly than did morphine and selectively antagonized quipazine-induced head twitches; its inhibition of head twitches induced by 5-hydroxytryptophan or LSD seemed unspecific. The results suggest that the opiate receptors involved in the inhibition of some symptoms of morphine abstinence and of the pinna reflex differ from those involved in opiate analgesia.


The effect of sera from chronic lymphocytic leukemia patients on normal mitogen-stimulated lymphocytes. A possible correlation with the patients' T and B lymphocytes. Serum from chronic lymphocytic leukemia (CLL) patients was examined for its effect on normal lymphocytes stimulated by phytohemagglutinin and pokeweed. Responses of the patients' lymphocytes were similarly examined. E and EAC rosettes were also tested. A significantly increased transformation response was found when normal lymphocytes were exposed to sera from those patients who had a reduced number of E-rosette-forming lymphocytes (mean 8%) as compared to the response to sera from patients with a higher number of E-rosette-forming cells. The results suggest that a factor is present in sera from some CLL patients which stimulates the transformation of mitogen-stimulated lymphocytes and which seems to be related to the number of the patient's T and B lymphocytes and perhaps with a T suppressor effect on B lymphocytes.


Hematopoiesis on cellulose ester membranes (CEM). II. Enrichment of the hematopoietic microenvironment by the addition of selected cellular elements. Cellulose ester membranes (CEM) were folded into a trilaminar open-ended tube which was implanted into the peritoneal cavity of mice. CEM rapidly acquired a stromal core with many features of marrow such as fat, fibroblasts, an abundant sinusoidal microcirculation and monocyte-macrophage-like cells. CEM took up 59iron, 99technetium sulfur colloid and produced CSF in in vitro culture but their microenvironment supported only granulopoiesis. CEM were coated on their interior surfaces with bone marrow or regenerating medullary cavity mesenchyme or bone but the stromal cores supported only granulopoiesis after 3 weeks to 3 months of implantation. CEM coated with spleen and implanted into mice developed trilineal hematopoiesis within 6 weeks with abundant erythropoiesis and megakaryocytopoiesis in addition to granulopoiesis. These CEM differed from splenic tissue in that only scattered lymphoid tissue was present. CEM coated with bone marrow and bone developed trilineal hematopoiesis but only after3--6 months of peritoneal implantation. CEM coated with regenerating medullary cavity mesenchyme failed to develop trilineal hematopoiesis. Cyclophosphamide injection did not enhance hematopoiesis. These experiments indicate that splenic, marrow and bone tissue contain stromal elements capable of being transferred onto CEM which then develop a microenvironment capable of supporting trilineal hematopoiesis.


Endotoxin-induced alterations in canine granulopoiesis: colony-stimulating factor, colony-forming cells in culture, and growth of cells in diffusion chambers. Salmonella typhosa endotoxin injected into dogs produced elevated plasma CSF levels, transient leukopenia followed by leukocytosis, and stimulation of marrow granulopoiesis and mobilization of granulocyte-macrophage progenitors cells into the the peripheral circulation. The number of marrow CFU-c decreased to 65% of the control number within 6 h, returned to control levels by 24 h, and increased to 370% of the control number by 48h after endotoxin. The granulopoietic response was supported by a concomitant increase in the M:E ratio, an increased fraction of marrow-derived CFU-c susceptible to 3H-TdR suicide, and increased granulo-monocytopoietic activity of marrow- and peripheral blood-derived cells grown in diffusion chamber cultures. These results are consistent with the concept that endotoxin-induced CSF is a physiologic regulator of canine granulopoiesis, and that canine marrow responds to endotoxin with a significant increase in the concentration of marrow-derived granulocytic progenitors and with mobilization of granulocyte-macrophage progenitors into the peripheral circulation.


Response characteristics of semicircular canal and otolith systems in cat. II. Responses of trochlear motoneurons. 1. The electrical activity of single trochlear motoneurons (TMns) and axons of second order vestibular neurons presumably terminating on these motoneurons were studied during natural stimulation of semicircular canals and otolith organs in cats anesthetized with Ketamine. 2. Null point analysis showed that TMns received an excitatory canal input from the contralateral posterior canal, and labyrinthine lesion experiments suggested that the functionally synergistic, ipsilateral anterior canal provides an inhibitory input. A small number of motoneurons showed orthogonal canal convergence. 3. In addition to the canal projections most TMns received an otolithic input. Firing rate was proportional to lateral head tilt and was of the beta type. Most units also responded to pitch with an increase and decrease in firing rate on nose-up and nose-down positioning, respectively. Lesion experiments indicated that the otolith responses are the results of reciprocal innervation of TMns by contralateral (excitatory) and ipsilateral (inhibitory) otolith projections. 4. During sinusoidal rotation in yaw (canal only stimulation) the mean phase lag re acceleration of the response of TMns increased from 60 degrees at 0.025 Hz to 126 degrees at 1.0 Hz. In roll (canal plus otolith stimulation) the phase lag of TMn responses measured 180 degrees and 130 degrees at 0.025 and 1.0 Hz, respectively. Phase-lags measured in Vi and Vc axons were less by ca. 15 degrees. 5. The otolith contribution to TMn responses in roll was calculated by vectorial subtraction of the yaw from the roll responses: A phase lag of 10 (0.025 Hz) to 90 degrees (0.5 Hz) re. displacement was noted and gain was constant over the same range. Similar lag dynamics were revealed in TMns when studied during ramp displacement of the head. 6. The possible functional role of central canal-otolith convergence and the differences between the response of primary vestibular afferents and secondary vestibular neurons and TMns will be discussed.


Experimental immune pancreatitis in the mouse by rabbit immune sera directed against purified enzymes of the exocrine pancreas. An experimental xenogeneic immune pancreatitis was induced in AB-mice by repeated intraperitoneal injections of rabbit immune sera directed against purified pancreatic enzymes (alpha-amylase, lipase, trypsin) for 3 hours up to 8 days. Histologically, the immune pancreatitis is characterized by three different findings: 1. Multiple acinar cell necroses on the 2nd, 3rd and 5th day of immune serum application. 2. A dedifferentiating acinar cell atrophy with development of pseudocanalicular acini on the 5th and 9th day. 3. An increasing interstitial histiolymphoplasmocytic pancreatitis on the 5th and 9th experimental day. Ultrastructurally, the acinar cell necroses proved as the final stage of a step-by-step developing acute lethal cell damage. The dedifferentiating acinar cell atrophy corresponds to a chronic sublethal cell injury with alteration of different cytoplasmic components. The interstitial pancreatitis in immune serum treatment is characterized by differently activated histiocytes and lymphocytes as well as by mature plasma cells. Because of immune histological findings (peri- and intraacinar deposition of rabbit globulin, specific fixation of guinea-pig complement, and appearance of mouse globulin in the mouse exocrine pancreas) and control experiments with rabbit and mouse normal serum as well as with physiological saline, the pathogenesis of the induced xenogeneic immune pancreatitis is regarded as a twophase process: 1. The acinar cell necroses are mainly due to a cytotoxic immune reaction (possibly in combination with an immune complex reaction) caused by specific anti-pancreatic enzyme antibodies of the applied immune sera. The dedifferentiating acinar cell atrophy may be the result of a specific action of the anti-enzyme antibodies against the corresponding pancreatic enzymes in the apical secretion granules of the pancreatic acinar cells. 2. The interstitial histiolymphoplasmocytic pancreatitis is mainly the morphologic substrate of an extravascularly (intraperitoneally) induced serum sickness reaction (immune complex reaction) due to the foreign proteins applied with the xenogeneic immune sera.


[Changes in the contractile properties of tonic muscle fibers following denervation]. After denervation, most of the tonic muscle fibers, contrary to intact fibers, cannot keep for a considerable time either the potassium (K) or the acetylcholine (A) contracture. The maximal mechanical tension in response to K and A in the denervated tonic fibers is lesser than in normal. The amplitude, speed of development, and latency (L) of the caffeine contracture remain practically the same. The speed of development of the K contracture sharply falls down and its L rather increases while the respective parameters of the A contracture practically do not change. The main changes developing after the denervation seem to occur in the processes controlling relaxation of the tonic fiber, as well as in the mechanisms for activation of K contracture while preserving the mechanisms for activation of A contracture.


Natural hemolytic activity of snake serum. II. Heterogeneity of putative natural antibody and levels of hemolytic activity. The erythrocytes of various vertebrates, such as mice, rabbits, sheep, chickens, bullfrogs, and toads are lysed by normal snake sera. However, snake erythrocytes were not lysed by serum from different snake species. Putative natural antibody seems with different specificities to comprise heterogeneous antibodies. Thus, absorption of snake serum with mouse erythrocytes, for example, abrogated hemolytic activity for mice but not for rabbit or sheep erythrocytes. We observed no significant intraspecies individual differences in serum hemolytic titer, but interspecies differences were obvious. Immunization of snakes with sheep erythrocytes caused no further elevation of hemolytic activity, though high titer antibody was produced in response to certain bacterial antigens. Even the sera of newly-hatched snakes showed hemolytic activity at modestly high levels. No seasonal change in hemolytic activity was observed.


Characterization of a differentiation-stimulating factor for mouse myeloid leukemia cells. Conditioned medium containing a differentiation-stimulating factor (D-factor) for M1 cells (myeloid leukemia cell line) was recovered over a period of several weeks by culturing mouse secondary embryo cells in serum-free medium but supplemented with bovine serum albumin. Incubation of M1 cells with the conditioned medium for 48 hr or less resulted in differentiation of 60 to 80% of the cells. From the conditioned medium, D-factor was partially purified by preparative electrophoresis on a Pevikon block and the specific activity was increased 50 approximately 60-fold. The partially purified D-factor was capable of differentiating 30% of the M1 cells at a protein concentration of 2 approximately 3 microgram/ml. Half-logarithmic plots of phagocytosis-inducing activity vs. protein concentration yielded a sigmoid dose-response curve. D-factor is considered to be a glycoprotein with a molecular weight of 40,000 approximately 50,000 and an electrophoretic mobility of alpha-globulin. It is resistant to different protein-denaturing treatments. Since the nature of D-factor differs from that of the colony-stimulating factor for mouse bone marrow cells, it appears that these two activities are due to different substances.


Studies on the subpopulation and function of peripheral lymphocytes, and lymphocyte reactivity to colonic mucosal antigen and bacterial antigen in patients with ulcerative colitis and Crohn's disease. Immunological studies were carried out in fifteen cases of ulcerative colitis, three cases of tuberculous colitis, four cases of Crohn's disease and one case of Behcet's disease diagnosed by X-ray, endoscopy or biopsy mainly from the standpoint of cellular immunity. In patients with ulcerative colitis the T-cell population and PHA responsiveness of peripheral lymphocytes were both depressed more than in the control group. At different stages of the disease, the deviation of the values of PHA responsiveness of lymphocytes showed a rather wide range in the active stage and there was also immunological instability. However, when the disease entered remission, the immunological conditions settled down and the pathological condition appeared stable. In contrast to the nonspecific immunological conditions mentioned above, characteristically, there were many examples of a positive lymphocyte response to colonic mucosal and bacterial antigens. In all cases of Crohn's disease the lesions are in the small intestine and there was a reduced response to PHA lymphocytic stimulation which was more pronounced than that in patients with ulcerative colitis. PHA response was also high in tuberculous colitis cases.


Binding studies of H-Y antigen in rat tissues: indications for a gonad-specific receptor. The binding capacity for H-Y antigen was studied in various rat tissues of both sexes. In nongonadal tissues (liver, kidney, brain, epidermis) binding could not be demonstrated. In contrast, the gonads are able to bind exogenously supplied H-Y antigen. In the ovary, the binding capacity remains unchanged in newborn and adult animals, while in the testis, this capacity decreases with age. A receptor like that of a proteohormone is assumed to exist in the gonads but not in other tissues. In nongonadal tissues, H-Y antigen apparently is present only if the cell itself synthesizes the antigen. The H-Y antigen receptor of the gonads is not sex-specific. Thus, the primary sex differentiation depends on whether H-Y antigen is synthesized in the organism.


PKU locus: genetic linkage with human amylase (Amy) loci and assignment to linkage group I. The linked alpha-amylase loci Amy 1 and Amy 2 were evaluated for their linkage relationship to the PKU locus using data collected from two (one Czech and one Polish) groups of families. The five sibships informative for Amy 1:PKU give a z score of 1.505 at theta = 0.00 and the eight sibships informative for Amy 2:PKU give a z score of 2.709 at theta = 0.00. Due to the tandem position of Amy 1 and Amy 2 loci, these data could be combined, and linkage between Amy and PKU loci established with a z score 4,214 at theta = 0.00. The practical significance of the linkage, especially for identifying PKU allele carriers, is emphasized.


Cell-mediated immunity in diabetes mellitus. Cell-mediated immunity was evaluated in patients with diabetes mellitus by delayed hypersensitivity skin tests and in vitro lymphocyte transformations. Only 44% of diabetic patients had skin test reactivity to Candida antigen, compared with 88% of normal controls (P < 0.001). Insulin-dependent diabetic (IDD) patients had abnormally low lymphocyte transformation responses to phytohemagglutinin, concanavalin A, and streptokinase-streptodornase (P < 0.05). This defect was not corrected by culturing the cells in nondiabetic plasma. IDD patients with persistent hyperglycemia (fasting serum glucose level, >200 mg/dl) had lower levels of transformation than did IDD patients with fasting serum glucose levels less than 150 mg/dl. Lymphocytes from two IDD patients with poor lymphocyte transformation responses had marked improvement in response to phytohemagglutinin when the lymphocytes were cultured after a preincubation period designed to deplete cultures of suppressor activity. Seven IDD patients were studied serially over 12 months. Lymphocyte transformation responses in four of these patients improved coincidentally with a change in the level of fasting hyperglycemia from >200 to <150 mg/dl. The other three IDD patients with consistent fasting serum glucose levels of >200 mg/dl had poor lymphocyte transformation responses. Diabetic patients have demonstrable defects in lymphocyte function which improved in a small number of patients with reduction in the level of fasting hyperglycemia.


Chromosome aberrations induced in human lymphocytes by radiation from 252Cf. In vitro dose--response curves of unstable chromosome aberrations in human lymphocytes have been obtained for 252Cf neutron radiation. The aberration yields fitted best to the linear function Y=aD, which is consistent with the single-track model of aberration formation for high LET radiation. The curves have been compared with others previously produced in this laboratory for several energies of neutrons and for 60Co gamma radiation. The r.b.e. for 252Cf with respect to 60Co is 27 at very low doses, decreasing to 6 at an aberration yield equivalent to 400 rad of 18 rad/hour gamma radiation. A profile of chromosome-aberration induction with depth in a perspex phantom was obtained by placing blood samples at several distances over the range 0.65-2.0 cm from the californium source. This profile was compared with depth-damage calculations for a radium needle. The r.b.e. of 252Cf radiation relative to 226Ra gamma radiation increased with the distance from the source, implying that californium is more effective at greater distances in destroying the ability of cells to divide, which may be an advantage in the treatment of large tumours.


Vertebral compression syndrome in multiple exostoses (case report). The authors present a case, the second in the world literature, of Spinal Compression Syndrome in Multiple Exostoses. The diagnosis, not revealed on standard radiographs of the vertebral column, was suspected on radiculography and confirmed only by oblique stratigraphic projection. These demonstrated bone formation on the right vertebral lamina of L4 encroaching considerably on the spinal canal. Surgical laminectomy was followed by complete remission of neurological symptoms.


[So-called nevoid forms of congenital poikiloderma]. The nevoid forms of poikilodermia as described in the literature are reviewed. The cases presented can be classified in better defined entities. The significance of a nevoid form of poikilodermia is doubted.


Synchronous division and rates of macromolecular synthesis in Haemophilus influenzae competent for genetic transformation. When competent Haemophilus influenzae were returned to complete growth medium, they resumed growth at once and underwent a synchronous division after 20 to 25 min. The rate of DNA synthesis increased to the definitive rate very quickly after resumption of growth. In contrast, the rate of RNA synthesis remained low until the time of division, at which time it accelerated dramatically. Changes in the rate of protein synthesis were similar in form to those of RNA synthesis. The kinetics of loss of competence upon resumption of growth had a pattern similar to the rate of RNA synthesis, and both processes accelerated markedly at the time of cell division, suggesting an inverse relationship between RNA synthesis and the ability to take up DNA.


Cell-mediated immunity during natural measles infection. Natural measles causes prolonged depression of cell-mediated immunity yet little is known as to how the infection influences lymphocyte function. Therefore, we studied the properties and function of lymphocytes during and after measles. The number and proportion of circulating thymus-derived lymphocytes was low during the acute stage of measles, and at this time 37% of these cells showed positive immunofluorescent staining for measles virus after stimulation with phytohemagglutinin. 7% of B cells were shown to contain virus but their numbers did not alter during the infection. Acute-phase lymphocytes, when stimulated, yielded infective virus and half were killed on incubation with autologous serum and complement. In acute measles the increase in [(3)H]-thymidine uptake of lymphocytes when stimulated with an optimal dose of PHA was normal in media with 10% fetal calf serum and low in media containing 10% autologous serum: the mean values were 56.8+/-34.1 and 23.7+/-25.9 cpm x 10(3) per 10(6) lymphocytes, respectively. Stimulation of acute-phase lymphocytes by Candida antigen was also low in media containing autologous serum averaging 1.2 x 10(3) cpm per 10(6) lymphocytes. On recovery 4-6 wk later this rose significantly to 18.9+/-19.8. The mean migration index of leukocytes to heat-killed candida cells in acute measles was 0.84+/-SD 0.08, and this fell significantly to 0.75+/-SD 0.08 4 wk later. Thus, depletion of T cells, an inhibitor of lymphocyte proliferation in the serum and a possible defect in antigen processing, interacts to depress cell-mediated immunity in measles.


Disulfide bonds and the quaternary structure of factor VIII/von Willebrand factor. Human Factor VIII/von Willebrand factor, purified by calcium citrate-cellulose chromatography and 4% agarose gel filtration was subjected to sodium dodecyl sulfate gel electrophoresis on gels containing 2% acrylamide and 0.5% agarose. We find a series of multimers of which the apparent molecular weight of the higher members was congruent with5 million. The higher multimers were isolated by 2% agarose gel filtration. Treatment of the high molecular weight multimers with 2-mercaptoethanol at concentrations of 0.005-0.5% in the presence of 1% dodecyl sulfate resulted in a shift to lower molecular weight multimers. Between mercaptoethanol concentrations of 0.01 and 0.5%, the predominant species was the dimer of the basic subunit. Mercaptoethanol concentrations >0.5% were required to reduce the interchain disulfide bonds of the dimer. An artificial multimeric series was prepared by cross-linking von Willebrand factor subunits with dimethylsuberimidate. Comparison of the multimers produced by reduction with the multimers produced by cross-linking, demonstrated the absence of odd-numbered multimers from the reduced series. Thus, the protomeric unit appears to be the dimer. High molecular weight multimers had both ristocetin cofactor activity and Factor VIII procoagulant activity. Reduction of the protein in the absence of denaturing agents, caused a gradual shift to lower molecular weight species and a concomitant loss of von Willebrand factor activity. In contrast, Factor VIII activity was unchanged by reduction. These studies suggest that the moieties having von Willebrand factor activity and those having Factor VIII activities are covalently linked by disulfide bonds.


Correlation of adenosine deaminase activity with cell surface markers in acute lymphoblastic leukemia. Adenosine deaminase (ADA) activity has been measured in the lymphoblasts of 23 untreated patients with acute lymphoblastic leukemia and related to the presence or absence of immunologic cell surface markers. The mean ADA activity in the acute lymphoblastic leukemia population as a whole was increased fourfold over that in normal lymphocytes. 9 of the 23 patients were classified as thymus-derived (T-) cell acute lymphoblastic leukemia on the basis of erythrocyte rosette positivity; the remaining 14 patients had null-cell leukemia. The mean ADA activity (ADA U/mg protein) of T-cell lymphoblasts (102 U) was 3 times higher than the mean of null lymphoblasts (30 U). This difference is statistically significant (P less than 0.02). Measurement of ADA activity offers a biochemical method of distinguishing between immunological subtypes of lymphoblasts which may be of prognostic and therapeutic value.


A serum inhibitor of immune regulation in patients with systemic lupus erythematosus. Normal mononuclear leukocytes were incubated with serum from patients with active systemic lupus erythematosus (SLE) and healthy subjects and then studied on lymphoproliferative tests. Serum from SLE patients that contained an autoantibody to a subpopulation of thymus-derived (T) lymphocytes inhibited suppressor T-cell activity induced with concanavalin A. These sera did not inhibit lymphoproliferative responses or suppression by monocytoid cells. Mitogen-activated suppressor cells were not inhibited with serum from SLE patients or healthy subjects lacking T-cell autoantibody. This abnormality may contribute to the altered immune response that occurs with SLE.


Senescent changes of the cornea.

Senescent changes of the cornea. In clinical optometry the practitioner often encounters that "gray area" concerning corneal changes of a senescent nature versus those that are not within normal limits and warrant referral. This paper provides a base line of information on corneal architecture and the physiology of the aging processes which take place within the tissue. This is followed by descriptions of the more commonly encountered senescent corneal changes and their clinical presentation.


Treatment of the chronic pain patient.

Treatment of the chronic pain patient. A small percentage of patients with persistent pain are sufficiently angry, demanding, and manipulative to require the negotiation of an explicit treatment and/or management contract. The very few studies in this field suggest that pain is both a function of and a stimulus to abnormal illness behavior, thus requiring special attention to therapeutic "ground rules." Treatment requires an unequivocal assertion by the patient that he wishes to get better and is willing to work at doing so; the specification of clearcut goals and the means of working towards them ("pacing behavior"); and the possible use of electrical neurostimulation and/or weak analgesics for pain control. Explicit understanding of mutual expectations and the patient's and doctor's "rights" is also helpful in fostering goodwill and desirable results.


In situ cytotoxic T cells in a methylcholanthrene-induced tumor. The in situ localization of cytotoxic T-cells was examined in a methylcholanthrene-induced fibrosarcoma. The MCA 2 tumor was initiated in this laboratory and utilized before extensive in vivo passage. Tumor cell suspensions were separated by unit velocity sedimentation. The T cell-enriched tumor-derived fractions and spleen cells from MCA 2-bearing mice were cytotoxic for in vivo isolated MCA 2 and in vitro cultured MCA 2 tumor cells, but not for SAD2 tumor cells. The cytotoxic activity of effector cells isolated from MCA 2 tumors was abrogated by treatment with anti-theta serum plus complement. The significance of cytotoxic T cells with in a progressing tumor is discussed.


Autoreactive antibody-forming cells directed against thymocytes and thymus-derived lymphocytes. Antibody-forming cells with specificities against syngeneic and allogeneic thymocytes are detected in the spleens of normal mice after activation in vitro or in vivo with lipopolysaccharide (LPS). The activity of such cells was measured in a complement-dependent plaque assay employing trypan blue dye to assess zones of lysis. Plaques were rarely seen in the absence of LPS treatment. Anti-immunoglobulin added to the plaque assay abrogated the appearance of plaques, but the addition of LPS had no effect. Furthermore, plaque formation was 2-mercaptoethanol sensitive indicating that the antibody responsible was of the IgM class. Plaque forming cells (PFC) were also detected against syngeneic and allogeneic lymph node cells and to a much lesser extent against splenocytes. The numbers of PFC found against syngeneic, allogeneic, or a mixture of thymocytes was similar and ranged from 1000 to 3000 PFC/10(8) viable spleen cells tested. All murine strains tested, including congenitally athymic nude mice, exhibited anti-thymocyte PFC after LPS activation. C3H/HeJ mice, genetically unresponsive to LPS, did not respond mitogenically to LPS and no anti-thymocyte plaques were observed. These findings suggest that clones of autoreactive B cells are present in normal mice and can be activated by LPS.


Further studies on the tumor-specific suppressor cells induced by ultraviolet radiation. Recent studies have suggested that the immunologic unresponsiveness of UV-irradiated mice against UV-induced fibrosarcomas might be due to the presence of suppressor lymphoid cells. In these experiments, we present additional evidence that suppressor lymphoid cells are present in lymph nodes and spleens of UV-irradiated mice and demonstrate that these cells are enriched after incubation on nylon wool columns, that they are inactive after treatment with anti-theta serum and complement, and that they are effective for at least 7 weeks after transfer to lethally x-irradiated mice. Splenectomy of UV-treated mice before tumor challenge did not restore their anti-tumor reactivity. The UV-induced suppressor cells appear to be specific for syngeneic UV-induced tumors, since they did not suppress the rejection of an allogeneic UV-induced tumor or two chemically induced syngeneic tumors.


Opposing reactivities of subpopulations of T lymphocytes toward syngeneic tumor cells: separation of early thymocytes. The present communication is a continuation of earlier studies which indicated that interaction between syngeneic tumors and those lymphocytes in the early stages of thymic processing can result in enhanced tumor growth in vivo. The thymocytes involved in this tumor enhancement were found previously in the rapidly dividing subpopulation of subcapsular cortical thymocytes, both in the untreated thymus and in the thymus undergoing repopulation after cortisone depletion. In the present experiments we have isolated this small subpopulation of early thymocytes. After cortisone injection such cells could be separated from the medullary cortisone-resistant thymocytes since the latter cells exhibit a high level of surface H-2 antigens and were thus lysed preferentially by anti-H-2 serum and complement. The repopulating subcapsular early thymocytes, which were resistant to this treatment, were incapable of responding to PHA while their basal proliferation rate was undiminished, and the majority of the cells were found to be dividing. When such low H-2 early thymocytes were injected together with three different tumors into syngeneic mice their tumor-enhancing activity was evident. It is clear that such early thymocytes are not devoid of biologic reactivity and their release from the thymus could have decisive results.


Chronic permeability of the central nervous system to mononuclear cells in experimental allergic encephalomyelitis in the Lewis rat. In order to assess whether experimental allergic encephalomyelitis (EAE), a putative animal model for multiple sclerosis (MS), is an ongoing chronic disorder, we have studied the permeability of spinal cords of Lewis rats with EAE to 3H-uridine- or 3H-thymidine-labeled lymphoid cells obtained from thymuses of naive donors or from draining lymph nodes of donors injected with guinea pig spinal cord + complete Fruend's adjuvant (CFA), guinea pig myelin basic protein + CFA, or with CFA alone. During the acute clinical phase of EAE there is a high-level infiltration of 3H-thymidine- or 3H-uridine-labeled cells into the spinal cords. After clinical recovery from EAE up to 58 days post-inoculation, there is a low-level infiltration of 3H-thymidine-labeled cells into the spinal cords. A similar infiltration into the spinal cords by 3H-uridine-labeled cells was not detected. Donor cells from animals immunized with CFA alone showed similar levels of infiltration into the spinal cords of animals with EAE as donor cells from animals immunized with the encephalitogenic emulsion. Spinal cords from recipients immunized with CFA alone showed no increased permeability to labeled cells. Heat-killed labeled cells did not migrate into the spinal cords of animals with EAE. We conclude that a) EAE is a chronic disease and in this regard is a valid model for MS; and B) in the chronic phase of EAE, recently divided cells (3H-thymidine-labeled cells) show higher levels of migration into the target tissue than 3H-uridine-labeled cells.


Characterization of a B cell defect in the NZB mouse manifested by an increased ratio of surface IgM to IgD. In an effort to define the cellular basis of abnormalities in polyclonal B cell activation previously noted in NZB mice, the surface immunoglobulin (sIg) isotypes of spleen cells from NZB mice were examined. After lactoperoxidase-catalyzed radioiodination, the cell surface immunoglobulins were analyzed by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). Spleen cells from 8- to 10-week-old NZB mice were found to have an increased ratio of cell surface IgM/IgD compared to cells from 11 control strains. The altered ratio of sIg isotypes was not a consequence of increased proteolytic activity present in NZB cell suspensions or of the presence of cytophilic antibody or autoantibody. Ontogenetic studies of the sIgM/sIgD (mu/delta) ration on splenocytes from NZB and BALB/c mice revealed that the former cells had higher mu/delta ratios as early as 2 weeks after birth. By 4 weeks of age the mu/delta ratios were equivalent. Between 4 weeks and 1 year of age, the mu/delta ratios on NZB splenocytes remained constant whereas those on BALB/c splenocytes decreased and reached adult levels at 6 weeks.


Functional significance of electrocardiographic changes after left ventricular aneurysmectomy. Electrocardiographic (ECG) changes after left ventricular aneurysmectomy were analyzed in 20 patients, thirteen of whom had additional aorto coronary saphenous vein bypass surgery. ECG changes were correlated with postoperative clinical and hemodynamic results. Out of 14 patients (Group I) who showed hemodynamic and/or clinical improvement, eight had decrease of chronic ST segment elevation that was associated in five with loss of pathologic Q waves. In the remaining six patients (Group II) who showed no hemodynamic or clinical improvement as well as in six patients in Group I, chronic ST segment elevation persisted or increased and in some, new pathologic Q waves developed after surgery. The study suggests that loss of pathologic Q waves and/or decrease of chronic ST segment elevation in patients who undergo a left ventricular aneurysmectomy with aorto coronary saphenous vein bypass surgery may reflect postoperative clinical, hemodynamic and angiographic improvement. On the other hand, failure of these ECG changes to occur or, conversely, increased ST segment elevation and/or appearance of new Q waves may have no predictive value. The mechanisms for these ECG changes are discussed.


Evidence for changes in segmental motoneurone pools by chronic cerebellar stimulation and its clinical significance. Electrophysiological studies in eight patients with severe motor system abnormalities are described both before and after the start of chronic electrical stimulation of the anterior cerebellum. With stimulation, at least one of following changes was found in seven of these eight patients: reversal of abdominal F amplitude ratios (flexor/extensor muscles), decreased prominence of F responses, and loss of H reflexes in at least one muscle other than the soleus. These changes indicate that cerebellar stimulation can affect the excitability of segmental motoneurone pools. Although clinical changes, particularly decrease in tone, were observed in all the patients with stimulation, the complexity of trying to relate the physiological findings to functional improvement is emphasised.


Relapsing neuropathy due to tetanus toxoid. Report of a case. A unique case history is presented, of a 42-year-old patient who has suffered three episodes of a demyelinating neuropathy, each of which followed an injection of tetanus toxoid. The clinical features on each occasion were characteristic of acute idiopathic polyneuropathy; a rapid onset of a mainly motor neuropathy with eventual recovery. Nerve conduction studies performed during the second and third episodes demonstrated grossly slowed motor conduction velocities. The sural nerve was biopsied after the third episode, and the features seen on light and electron microscopy included prominent hypertrophic changes, mononuclear cells associated with most "onion bulbs" and macrophage mediated demyelination. Studies of blastogenesis and macrophage migration inhibition, showed T lymphocyte responsiveness to both peripheral nerve myelin and tetanus toxoid. Typing for antigens of the HLA system indicated that the patient was homozygous for HLAB8.


DNA and RNA antibodies in serum and CSF of multiple sclerosis and subacute sclerosing panencephalitis patients. DNA and RNA (nucleic) antibodies were found in the CSF of 18 patients with multiple sclerosis (MS) (out of 45), 11 with subacute sclerosing panencephalitis (SSPE) (out of 12) and 9 controls (out of 30). Viral (measles and rubella, by HAI) antibodies were present in all SSPE, 23 MS and 11 control patients. A clear correlation exists between (1) CSF immunological patterns, (2) oligoclonal aspect, (3) simultaneous presence of nucleic and viral antibodies, suggesting the local synthesis of both. This is confirmed by the comparison of the ratios IgG/antibodies in serum and CSF: the CSF ratio may be higher for nucleic and/or viral antibodies in SSPE and MS patients. Thus nucleic antibodies seem to be related to a persistent active infection within the central nervous system.


Effect of TMP-SMX on nasopharyngeal carriage of ampicillin-sensitive and ampicillin-resistant hemophilus influenzae type B. The carriage rate of ampicillin-resistant Hemophilus influenzae type B in a chronic care facility was investigated. Up to 48% of the children carried this strain. Of interest was the finding of simulaneous carriage of ampicillin-resistant and ampicillin-sensitive HITB, a phenomenon which was detected by using both chocolate agar and chocolate agar containing 2 microgram/ml of ampicillin. A trial of sulfamethoxazole-trimethoprin successfully eradicated the ampicillin-sensitive HITB, but had no effect on the ampicillin-resistant HITB.


Maintenance of low sodium and high potassium levels in resting muscle cells. 1. Previous work has shown that a frog sartorius muscle consists of parallel cells running all the way from one end of the muscle to the other and that amputation of one end of the muscle is not followed by regeneration of a new cell membrane. If now only the cut end of the amputated muscle is exposed to a Ringer solution in which the solutes 42K and 22Na act as radioactive labels and the rest of the cell is suspended in air, we have what is described as an effectively membraneless open-ended cell or EMOC preparation. In this case the only remaining anatomically intact plasma membrane and pumps are made nonfunctional by the removal of 'sources' for inward pumps and 'sinks' for outward pumps. 2. The healthy region of a frog sartorius muscle EMOC preparation continues to accumulate labelled K+ to a level higher than that in the Ringer solution and to exclude labelled Na+ to a level below that in the Ringer solution, much as a normal uncut muscle does in its normal environment. The differences were reduced by inclusion of ouabain in the medium. 3. The diffusion coefficient of Na+ in the normal muscle cytoplasm at 25 degrees C was measured using two methods. The average diffusion coefficient measured was 2.07 X 10(-6) cm2/sec, roughly 1/6 that of the diffusion coefficient of Na+ in a 0.1 N-NaCl solution. 4. The data obtained are discussed in terms of the association-induction hypothesis. In this theory asymmetrical solute distribution, basically an expression of a non-energy consuming metastable equilibrium state, is the result of specific combinations of two opposing mechanisms: adsorption which raises the level of the intracellular solute; and exclusion from cell water which tends to lower it.


A potential- and time-dependent blockade of inward rectification in frog skeletal muscle fibres by barium and strontium ions. 1. A three-electrode voltage clamp method was used to investigate the effects of Ba and Sr ions on the inwardly rectifying K conductance of resting frog sartorius muscle fibres. 2. When Ba2+ (0.01-5 mM) was added to the control (115 mM-K+) solution the inward currents recorded during hyperpolarizing voltage steps turned off exponentially with time as the blockade by Ba2+ developed. Outward currents showed no time-dependence. 3. Ba2+ ions reduced both the instantaneous and the steady-state values of currents recorded on hyperpolarization. The blockade was potential-dependent, steady-state currents being increasingly reduced with increasing hyperpolarization. 4. The concentration-effect relation for the blockade of instantaneous currents by Ba2+ could be fitted assuming 1:1 binding of Ba2+ to a receptor, with the block being proportional to the number of Ba2+-filled receptors. The apparent dissociation constant at the holding potential (-5 mV) was 0.65 mM. Concentration-effect relations were shifted along the concentration axis to lower concentrations by hyperpolarization. The apparent dissociation constant was reduced e-fold for a 16.8 mV change in potential. 5. Increasing the [Ba]o increased the rate of onset of the blockade at a given potential. 6. The rate of onset of the blockade had a high temperature dependence (Q10 = 3.15 +/- 0.08). 7. When [K]o was doubled to 230 mM, under conditions where [K]i was also doubled, [Ba]o had to be raised approximately fourfold to produce the same degree and rate of onset of blockade. Similarly, when [K]o was decreased, the degree and rate of onset of blockade were increased for a given [Ba]o. 8. The blockade could be readily removed by removal of Ba2+ from the bathing solution. In addition the blockade which develops on hyperpolarization is removed exponentially on return to the holding potential. 9. The blockade which exists at the holding potential may be removed by a depolarizing prepulse. 10. Sr causes a similar potential-dependent blockade to that by Ba2+, but is around 400 times less effective. 11. The results have been fitted with a model assuming that the permeability mechanism is an aqueous pore with a site which binds one Ba2+ ion or two K+ ions. The site must have affinity for Ba2+ and a low affinity for K+.


Reversible depletion of synaptic vesicles induced by application of high external potassium to the frog neuromuscular junction. 1. Reversible depletion of synaptic vesicles from frog cutaneous pectoris neuromuscular junctions was studied by application of a Ringer solution containing 115 mM-K propionate.2. During the release of transmitter, the synaptic vesicle membrane is added to the axolemmal membrane. Under the conditions of high K(+)-induced release, the synaptic vesicle membrane accumulates as folds formed in the region of the axolemmal membrane between the active zones. In depleted terminals, large vesicular structures appear and the evidence shows that some of them (possibly all) are formed as axolemmal infoldings. During formation of such infoldings the active zones remain fixed in position with respect to the post-junctional membrane.3. During recovery in normal Ringer solution, which followed 30 min depolarization in high K(+) Ringer solution, spontaneous m.e.p.p.s were detected as early as 9 min after the start of the recovery period and the average time for their reappearance was 17 min.4. At the end of a 20 min recovery period which followed K(+) depolarization, small accumulations of synaptic vesicles were again found within the terminal close to the active zones. At this time coated vesicles and coated pits were seen associated with the prejunctional axolemma and its infoldings. It appears that synaptic vesicles are re-formed directly from these coated vesicles.5. After 60 min recovery from K(+) depolarization, at which time stimulation of the motor nerve induced a muscle twitch, the structure of the terminals closely resembled that of control preparations.6. The entire synaptic vesicle recycling process can take place in the absence of the neurone soma.


Potassium efflux in heart muscle during activity: extracellular accumulation and its implications. 1. Extracellular K+ activity and transmembrane potential were simultaneously monitored with a K+-selective micro-electrode placed in the extracellular space and a standard KCl-filled micro-electrode in the intracellular space of the frog ventricular muscle. 2. K+ was found to accumulate during activity and had the approximate magnitude and time course to account for the measured membrane depolarization. 3. The magnitude of the K+ accumulation depended on the frequency of stimulation, diameter of the muscle and temperature of the bathing solution. 4. The time constants of accumulation and decay were dependent only on the diameter and the temperature of the strip. A Q10 of 2 was measured for the decay of accumulated K+. 5. Double barrelled K+-electrodes were used to monitor the change in K+ activity accompanying a single action potential, since the reference barrel allowed for rapid compensation of the electrical potential fluctuations encountered in the subendothelial space. 6. K+ accumulated continuously during the plateau to a level which increased external K concentration by about 1 mM. This increase in the subendothelial space corresponds to about 1-3 muA/cm2 or 10-30 pmole/cm2-sec-1 of net K+ efflux. These values are at least an order of magnitude larger than required to discharge the membrane capacitance. 7. There is no direct relation between action potential duration and rate of development or magnitude of K+ accumulation during that action potential. 8. Increase in the external K concentration, while shortening the action potential and depolarizing the membrane, does not lead to an increased rate of accumulation of K+. The presence of Ni2+, on the other hand, prolongs the action potential and decreases the rate of K+ accumulation. 9. The results suggest that there is a substantial and continuous efflux of K+ during the action potential, which sums during rapid beating, resulting in membrane depolarization and alteration of action potential duration. The change in action potential duration in response to rate may be caused by alteration of EK in the local micro-environments.


Detubulation effects on the action of zinc on frog skeletal muscle action potential. Detubulation of the untreated fiber decreases the time constant of the action potential's foot (tauf) and increases the maximal rate of rise of the spike (Vmax). Zinc at all concentrations, and regardless of whether the fiber is intact or detubulated, increases tauf and decreases Vmax, and thus seems to decrease Na activation of the fiber. Detubulation was used principally to elucidate the localization and mechanism of the Zn2+-induced retardation of the falling phase of the frog sartorius fiber action potential, which evidently results from a general depression of delayed rectification. At 50 to 1000 mum, Zn2+ not only prolongs repolarization of intact fibers (measured by increase in t0.5, the half-time of the spike's fall), but also produces a marked hump early in this phase. Detubulation of zinc-free fibers reduces t0.5 to about 80% of its intact value, and under Zn2+ treatment t0.5 is increased but only to about 80% of that produced in the inus, detubulation decreases t0.5 in Zn2+-treated fibers not only to about 80% of that produced in the intact fiber, and the falling-phase hump is completely obliterated. Thus, detubulation decreases t0.5 in Zn2+-treated fibers not only by generally eliminating T-tubular participation in action potential generation, but also by subtracting a Zn2+-induced retardation of tubular delayed rectification. Tubular delayed rectification must therefore be an intrinsic feature of normal excitation. These results are further analyzed by means of (i) Stanfield's findings about retardation of delayed rectification by Zn2+ and (ii) Adrian-Peachey's theory of T-tubule participation in action potential generation, which suggests that the Zn2+-evoked repolarization hump signals onset of Zn2+-altered active participation of T-tubules in determining the spike's shape.


Ultraviolet carcinogenesis in T-cell-depleted mice. The induction of skin tumors by chronic UV irradiation was compared in normal C3H/HeN(MTV-) mice, T-cell-depleted mice, and T-cell-depleted mice reconstituted with thymus grafts. The T-cell-depleted mice were thymectomized as young adults, lethally X-irradiated, and repopulated with neonatal liver cells. Skin tumors appeared earlier in the immunosuppressed T-cell-depleted mice than in the normal mice. However, tumors developed most rapidly in the group that was T-cell depleted and immunologically restored with thymus grafts. In the latter group, most of the tumors were squamous cell carcinomas, whereas in the normal mice, fibrosarcomas predominated. These experiments illustrated the limitations of this approach to studying the role of the immune response in carcinogenesis.


BN rat myeloid leukemia transferred to the (LEW x BN)F1 rat. The BN rat myelocytic leukemia was transferred to (LEW x BN)F1 rats. In the F1 host the growth, dissemination, and response of this leukemia to chemotherapy were predictable, stable through serial passage, and similar to this leukemia's behavior in the parent strain. Rats given 10(7) spleen cells iv from leukemic donors died in about 3 weeks if untreated or responded to cytosine arabinoside even after overt leukemia had developed. This animal leukemia is useful as a model for human acute myelocytic leukemia.


Vestibular-optokinetic interactions in normal subjects and in patients with peripheral vestibular dysfunction. The vestibulo-ocular reflex (VOR) during rotation, optokinetic nystagmus (OKN), and interactions between the vestibulo-ocular and optokinetic systems were studied quantitatively in 10 normal human subjects, 15 patients with unilateral horizontal semicircular canal paralysis (UP), and 11 patients with bilateral horizontal semicircular canal paralysis (BP). The OKN gain (eye velocity/drum velocity) was not significantly different between the normal subjects and the patient groups. During tests in which rotatory and visual stimuli were presented simultaneously, the contribution to the observed eye movements by the VOR was only one-fourth to one-third of its gain during rotation in the dark in the normal subjects and UP patients. These interactive tests did not differentiate UP patients from normal subjects but did separate BP patients from normal subjects.


Effects of gustatory stimulants upon the olfactory epithelium of the bullfrog and the carp. Effects of various gustatory stimulants upon the olfactory spithelia were examined in the olfactory bulb of the bullfrog and the carp. 1. The olfactory epithelia of the two animals responded to the salty, bitter- and acid-tasting substances, but not to the sweet ones. 2. The olfactory epithelium of the bullfrog responded immediately to sodium solutions of high concentrations (the "initial response"), but the response to those of low concentrations showed long latency (the "delayed response"). In the carp, the "initial response" was found, while the "delayed response" was not in most cases. A "negative" delayed response was found only infrequently. 3. Responses only to high alkali or acid solutions were found in the two animals. 4. When 0.05 M NaCl was added to HCl solutions, an enhancing effect was found in the bullfrog, while a reducing effect occurred in the carp. On the contrary, when 0.05 M NaCl was added to NaOH solutions, an enhancing effect occurred in the carp, while no consistent result was founding the bullfrog.  5. Many amino acids were effective stimuli in the bullfrog, but only betaine and 1-aspartic acid were found effective in the carp. 6. Changes in temperatures beyond 35 degrees C or under 10 degrees C elicited responses. Mechanical stimuli were effective in the carp, but not in the bullfrog. 7. The "water response" was found in the bullfrog, but not in the carp. 8. Sensitivities of the olfactory epithelia of the two animals were compared and discussed.


Ionic stimulation of the olfactory epithelium in the bullfrog and the carp. The stimulating effects of mono- and divalent cations and anions were studied in the olfactory epithelia of the bullfrog and the carp. The rhythmic waves induced by these ions were recorded in the olfactory bulb. 1. Many mono- and divalent cations and anions showed stimulating actions in the bullfrog and the carp. 2. Microelectrode studies disclosed that the olfactory receptor cells respond to different ions differently. 3. When many ions were applied with various concentrations, responses appeared with long latencies while the concentration was very low (the "delayed responses"). The responses nearly disappeared at the intermediate concentrations, but then responses with short latencies appeared at the higher concentrations (the "initial responses"). Thus, many ions showed dual responses in the bullfrog, although some exceptional cases were found (choline+, Tl+, La3+, Cd2+). 4. Cd2+ and other heavy metal ions showed depressive actions upon the responses induced by other ions in the olfactory epithelium. 5. Tetrodotoxin of even 10 (-5) g/ml was found ineffective in depressing the rhythmic waves induced by ions. 6. Chemoreceptive activities of the olfactory epithelia of the bullfrog and the carp were compared with the activities of the gustatory receptors. They were also compared with the other chemoreceptors of the fish, namely the palatal organ, external chemoreceptors over the snout region and the lateral-line organ. Chemical senses of the fish were discussed.


Stimulation of the olfactory epithelium with odorants in gaseous and aqueous phases. The olfactory epithelia of the bullfrog and the carp were stimulated with various odorants in the gaseous and/or aqueous phases. Some ionic solutions were also applied. 1. By recording the induced waves in the olfactory bulb, it was shown that the bullfrog responds to odorants in the two phases, but the carp can respond only to odorants in the aqueous phase. 2. Comparison of the stimulative effects of the same odorants in the two phases were made in the bullfrog. Although various response patterns to gaseous and aqueous stimuli of single cells in the olfactory bulb were found in most cases, a difference in the application methods of vapors and solutions made such comparison difficult. 3. The same single cells in the olfactory bulb usually responded to various odorous vapors and solutions as well as to ions in different patterns. When the responses to the vapors and solutions of the same odorants of different concentrations were compared, different patterns were also found.


Seasonal change of membrane potential across the proximal tubular epithelium in bullfrog kidneys. In order to examine the seasonal changes in the relationship between the membrane potential and potassium activity of proximal tubular epithelium, a micropuncture study was performed with potassium selective microelectrodes on the kidney of the bullfrog (Rana catesbeiana) in two different seasons: winter (7 degrees C) and summer (20 degrees C). The potasssium activity in winter animals (7 degrees C) was 2.92 +/- 0.33 (mean +/- S.D., n = 20), 63.2 +/- 12.7 (n = 26), and 2.68 +/- 0.19 (n = 26) mM for the tubular fluid, cell, and plasma, whereas that in summer animals (20 degrees C) was 2.84 +/- 0.05 (n = 22), 61.8 +/- 11.2 (n = 24), 2.63 +/- 0.24 (n = 24) mM, respectively, indicating no seasonal difference. On the other hand, the mean values of the membrane PD in winter animals were 59.4 +/- 1.8 (n = 26) and 71.7 "/- 7.2 (n = 26) mV for the luminal and peritubular borders, whereas those in summer animals were 55.1 +/- 1.7 (n = 24) and 63.9 +/- 6.9 (n = 24) mV, respectivley, indicating that there was a significant seasonal difference (p less than 0.05 and p less than 0.001). Hence, compared to winter animals, the changes in the electrochemical profile for potassium in summer animals were: 1) the peritubular membrane PD is lower and 2) the transtubular electrochemical gradient is less steep. The sodium permeability calculated  as the best fitting for a modified Goldman equation was 0.01 and 0.03 for winter and summer animals, respectively. In view of the fact the potassium in the cell and luminal fluid of the proximal tubule is kept at similar levels, potassium homeostasis is maintained in both groups of animals. The seasonal changes in electrical potentials are probably be due to an increase of cellular membrane permeability to ions other than potassium and to increased paracellular shunt conductance through the epithelium.


Effect of low temperature on the membrane currents and tension components of bullfrog atrial muscle. In order to clarify the nature of inotropic action of low temperature, the effects of cooling on the membrane currents and tension components were studied on the bullfrog atrial muscle under voltage clamped and unclamped conditions with double gap method. Cooling (in between 35 degrees-7 degrees C) produced an increase of overshoot and a prolongation of the action potential accompanied by a slight depolarization of the membrane, a decrease of basal tension and an increase of twitch contraction. Under voltage clamp, a marked augmentation of contraction also occurred despite a decrease of basal tension, suggesting that the inotropic effect of cooling is not merely dependent on the prolongation of action potential. When the components of membrane current and tension were isolated in modified Ringer solutions, it became clear that ICa and ICa -dependent tension markedly increased at low temperature, while all other currents (INaf, INas, IK1 Ix) and ICa-independent tension decreased. Leaky membrane current (I1) for hyperpolarizing pulses also diminished. Temperature coefficient (Q10) of the ICa-independent tension component was 1.2-1.5 between 7 degrees C and 17 degrees C, while that of ICa-dependent tension varied depending on depolarization voltages. These data were discussed in relation to possible alteration of Ca concentration at outer and inner layers of the membrane which may depend on temperature.


[Effect of abdominal aortic clamping on the kallikrein-kinin system and the activity of lactate dehydrogenase and its isoenzymes during reconstructive operations]. To study the effect of abdominal aorta clamping and revascularization and appraise the efficacy of the drug gordox during surgical intervention, the values of the kinin system, acid-base balance, acid metabolites, and the total activity of lactic dehydrogenase and its isoenzymatic spectrum were determined in 24 patients with aortic stenosis of atherosclerotic origin. In patients who did not receive gordox, the kinin system became markedly activated after the clamp was removed from the aorta, which led to a sharp fall in arterial pressure, the development of metabolic acidosis, and activation of enzymes of the glycolytic cycle. Preventive administration of gordox in the other group of patients during operation inhibited the processes of activation of the kinin system, stabilized hemodynamics, improved tissue circulation and prevented the development of hypoxia.


[Role of the sympathetic-adrenal and kallikrein-kinin systems in regulating central hemodynamics in acute experimental occlusion of the terminal portion of the aorta]. The role of the sympatheticoadrenal and kallikrein-kinin systems in the pathogenesis of hemodynamic disorders was studied in 29 dogs with acute experimental occlusion of the terminal part of the aorta. Data confirming the close dependence of the indices of central hemodynamics on the activity of the sympatheticoadrenal and kallikrein-kinin systems are presented. Close positive correlative connection between activation of the sympatheticoadrenal and kallikrein-kinin systems was revealed. The possible mechanisms of the correction of hemodynamic disorders in severe degree of ischemia by means of agents blocking the kallikrein system are discussed.


Treatment of hereditary angioedema.

Treatment of hereditary angioedema. The purpose of this study was to report the results of different treatments in 20 patients with hereditary angioedema. Effectiveness of tranexamic acid in preventing swellings was evaluated in 15 patients: in all but 3 subjects tranexamic acid was effective without serious side effects. 15 severe attacks of edema were managed with intravenous infusions of either kallikrein inhibitor (8 cases) or concentrate of C1 esterase inhibitor (7 cases). In only 1 case was the kallikrein inhibitor unsuccessful.  C 1 esterase inhibitor concentrate proved highly effective in the treatment of acute attacks (the result was lacking in one patient because of too low dosage of the drug). No side effects were observed with both treatments, but improvement was more rapidly achieved with infusion of C1 esterase inhibitor. The serum levels of C4 and C1 esterase inhibitor and the activity of C 1 esterase inhibitor before and after long-term prophylaxis and acute attacks treatment were investigated.


Effect of operation on B and T lymphocyte counts. Preoperative and postoperative studies of peripheral B and T lymphocyte counts were accomplished in 21 patients. Diagnoses included 10 carcinoma of the breast, 3 sarcoma, and 8 benign diseases. On postoperative day one and two, an increase in B-cell percentage was observed in the majority of patients tested. However, there was a decrease in total lymphocyte count and fast-reacting T lymphocyte numbers on postoperative day one, especially in patients who had intraabdominal operations. All the lymphocyte counts returned to preoperative range within one week. Pertinent reports in the literature were reviewed and discussed.


[Characteristics of vestibular nystagmus in rats]. As a result of experiments on Wistar, Wistar-SPF and mongrel rats, the duration, number of beats and frequency of nystagmus in response to progressively increasing acceleration of 10, 20, 30 and 40 deg/sec2 for 3 sec at each step were determined. These parameters were found to increase with a rise in acceleration, the rate of increase being gradually slowed down (the slope of the curves decreased). The number of beats and the duration of the nystagmus in the Wistar and mongrel rats were identical and significantly higher (P less than 0.01) than those in the Wistar-SPF rats. There was no difference in the nystagmic frequency. It was demonstrated that the system of animal restraint produced a noticeable effect on the quantitative characteristics of the nystagmus, e. g. duration and number of beats. The paper describes a system of gentle restraint of rats.


Age related differences in cellular immune response to vaccine induced rubella infection. Employing the techniques of in-vitro lymphocyte transformation (LTF) and using Putnam strain of rubella virus as the antigen, the development of rubella specific cellular immune response was studied in different age groups of rubella seronegative normal subjects at various intervals after subcutaneous administration of HPV=77/DE5 live attenuated rubella vaccine. The rubella specific lymphocyte response in children ranging in age from two to twelve years was characterized by significant LTF activity at two months, followed by a gradual decrease. The response in adult subjects 18 to 35 years of age showed a slight delay initially in the appearance and the maximum LTF activity appeared to be 3--4 fold lower (P less than 0.01) than observed in the children. No difference was observed in the maximum antibody titers to rubella virus between these two groups of subjects. These observations suggest that the age related differences in the lymphoproliferative responses might be associated with adverse effects which are known to occur more frequently in adolescent and older patients than in childhood population after vaccine induced rubella infection.


[Sport and prolongation of life (author's transl)]. In a retrospective study a group of 80-year-old men (114) were compared with regard to their living habits with a group of men from the same firm (131) who had died before the age of 65. The aim of the study was to present factors which could possibly affect the limitation of life expectancy. By means of electronic data processing the findings of the investigation and historical data (family history, personal history, risk factors, physical activity, occupational and social status) were evaluated and possible correlations looked for. The cause of death was particularly included in the interpretation. The risk factors of greatest importance were: cigarette smoking, adiposity, little physical activity.


[Recent aspects of the chemotherapy of malignant tumors (author's transl)]. The results of basic research of proliferation kinetics and pharmacokinetics as well as comparative clinical studies led to the development of therapeutic principles for malignant diseases. Thus polychemotherapy is to be preferred to monotherapy in most types of disease. To prevent primary resistance only those cytostatics should be combined which have been proved effective or could be expected to be effective individually. The relative cell cycle specificity of cytostatics should be taken into account by combination of drugs acting at different phases of the tumor cell cycle. The different growth behavior of tumor and normal tissues suggest the use of intermittent stoss therapy for the regeneration of normal tissue in the therapy-free interval.


Systemic membrane defect in the proximal muscular dystrophies. We studied lymphocyte capping in 61 patients with Duchenne, Becker, limb-girdle, facioscapulohumeral and congenital muscular dystrophies. All showed a markedly diminished percentage of capped cells when compared with 86 normal controls, providing support for previous evidence that an alteration in membrane fluidity may be a common pathogenic feature in several genetically distinct forms of proximal muscular dystrophy. Heterozygous carriers of Duchenne muscular dystrophy showed diminished capping that was indistinguishable from that of afflicted males and was often present even when serum enzyme levels were normal. Studies in 25 families with 16 suspected sporadic cases indicated that no more than four out of 30 afflicted males may represent new mutations. These findings imply that most cases of Duchenne dystrophy might be prevented by a population screening program for carrier females combined with prenatal detection of afflicted males.


Serum 1,25-dihydroxyvitamin D levels in normal subjects and in patients with hereditary rickets or bone disease. The serum concentration of 1,25-dihydroxylvitamin D (1,25-[OH]2D) in normal children and in children with inherited diseases of bone was compared by use of a competitive binding assay. Observed values were: in 12 normal children and adolescents, 37.1 +/- 1.9 pg per milliliter (mean +/- S.D.); in 14 patients with X-linked hypophosphatemic rickets treated with vitamin D2 and phosphate supplements, 15.6 +/- 7.8 (P less than 0.01 versus control); in six patients with autosomal recessive vitamin D dependency treated with vitamin D2, 9.5 +/- 2.9 (P less than 0.01 versus control); and in four untreated patients with autosomal dominant hypophosphatemic (non-rachitic) bone disease, 30.2 +/- 6.3 (not significantly different from the controls). The difference in bone disease between X-linked hypophosphatemia (severe) and hypophosphatemic bone disease (mild) at comparable low serum levels of phosphate implies that 1,25-(OH)2D and phosphate may have independent roles in the pathogenesis of defective bone mineralization.


Stages of the development of immunologic response in regional lymph nodes draining breast cancer. During the studies of regional lymph nodes originating from 50 patients with breast cancer, there were distinguished four stages in development of immune response. The first, stage of induction of the response concerned patients with non-infiltrating carcinoma. The second stage of the active immune response was observed in 1/3 of the patients with infiltrating cancer without metastases. In these cases, in the pattern of regional lymph nodes predominated medium sized lymphocytes within the thymus-dependent inner cortex, while in outer areas there was an increased number of small active follicles. Within the sinusoidal structures there predominated proliferating prohistiocytes growing in interaction with small lymphocytes. The third stage of immune response was characterized by weak activity and progressive cortical strophy of the lymph nodes and it was observed in 2/3 of the patients with invasive cancer. The fourth stage of immunologic response concerned the patients with minute-metastases within the regional lymph nodes. In these cases one group of the lymph nodes showed unstimulated pattern while the other a highly stimulated pattern with the presence of giant follicles.


Further observations on the use of 5-hydroxytryptophan in a child with Lesch-Nyhan syndrome. The effects of 5-hydroxytryptophan (5-HTP), a serotonin precursor, and carbidopa, a peripheral aromatic amino acid decarboxylase inhibitor, were studied in a boy with the Lesch-Nyhan syndrome. No effects on the self-mutilating behaviors of this disorder were noted. However, sleep patterns were normalized, with a reduction in the proportionate amounts of wakefulness and an augmentation of active sleep. A sharp reduction in waking behavioral dyskinesias was also correlated to increased drug dosage.


[Experience in the treatment of bleeding esophageal varices]. Personal experience with respect to the diagnosis and treatment of bleeding oesophageal varices in patients with cirrhosis is described. Diagnosis is directed both to the establishment of the site of bleeding and the disease responsible and to the evaluation of risk in view of the possibliity of portal decompression. Treatment is aimed at stopping bleeding and at lowering this risk so that as many patients as possible can be operated with an acceptable degree of surgical risk.


[Epidemiological study of emergency surgical pathology in the first aid department of a large hospital]. During a two-year period, major operations were performed on 874 males and 649 females at the first-aid section of a major hospital. Acute appendicitis was the most common intraoperative diagnosis (45.63%), followed by intestinal obstruction (21%), gastroduodenal perforation (6.83%), abdominal injury (5.98%), angiosurgical emergency situations (5.19%, including amputation for gangrene), gynaecological emergency situations (3.74%), acute cholecystitis (3.35%), haematemesis (1.44%), acute pancreatitis (1.31%), and various other diseases. Further surgery as a result of complications was required in 2.63%. Mortality (1 year only) was 7.42%. The results achieved and the tactical criteria employed are discussed.


[Possibilities of splenorenal anastomosis in portal hypertension]. The classical splenorenal shunt of Linton modified by Clatworthy is definitely superior to portocaval anastomosis. Between 1968 and 1976 in 225 patients with bleeding oesophageal varices a splenorenal anastomosis was performed in 47 cases, a portocaval in 30 cases and a mesentericocaval in 2 cases. There were 55 palliative operations as compared with 91 conservative therapeutic approaches. Over the last five years central termino-lateral splenorenal anastomses have been performed almost exclusively.


[Effect of neuropharmacologic preparations and colchicine on morphogenetic processes in embryonal amphibian cells]. The effect of antagonists of biogenous amines (antitransmitters--AT) and colchicine on rapid morphogenetic processes in the explants of embryonic ectoderm with underlying mesoderm cut from the lateral region of Rana temporaria embryos at the late neurula-early taibud stages was studied. The normal morphogenesis of the explants consists of two successive phases: phase of contact polarization and phase of cell movement into the fragment. The high concentrations of AT inhibited completely the morphogenesis of explants but somewhat lower concentrations inhibited the second phase of morphogenesis and not only did not prevent the cell polarization but even assisted its propagation over all the fragment. The inhibiting effect of AT was relieved by 5-hydroxytryptamine which per se stimulated the morphogenesis of explants. Thus, AT exert a specific inhibition of the motility of embryonic cells but do not prevent the contact interactions responsible for cell polarization within every layer.


Changes in somatic sensitivity during transcutaneous electrical analgesia. Patients with chronic pain in one limb, who experienced pain reduction with transcutaneous neurostimulation, were examined for sensory perception in that limb before and during electrical analgesia. Contralateral limbs and normal subjects served as controls. Sensory stimuli were quantified, a range of stimuli were presented and data were analyzed according to sensory decision theory. Results showed that, compared to controls, painful limbs show considerable impairment in sensory sensitivity. With transcutaneous neurostimulation, however, sensitivity is improved towards normal, whereas electrical stimulation slightly impairs perception in normal limbs. These results suggest that electrical analgesia involves both peripheral small-fiber blockade and large-fiber stimulation; the latter is more noticeable in the normal limb, but the former effect is predominant when pain reduction occurs in a painful limb.


[Post-haemorrhagic encephalopathy in cirrhosis. Prevention by digestive irrigation with 100 mg/l mannitol (author's transl)]. Rapid digestive irrigation makes it possible to remove all the blood contained in the intestine of the cirrhotic suffering from a gastrointestinal haemorrhage. With this procedure, used 62 times during 110 haemorrhages occurring in 57 patients with portal hypertension due to cirrhosis, there was statistically significant prevention (p is less than 0.001) against complications of post-haemorrhagic encephalopathy, but there was no action where neurological and psychiatric problems had already developed. The excellent tolerance of mannitol in a concentration of 100 mg/l, and in particular the absence of any untoward effects on water and electrolyte balance, made it possible to reduce fluid intake to 2000 ml in 2 hours without diminishing its effectiveness, the technique thus being simple and easy to apply.


In vivo induction of normal differentiation in myeloid leukemia cells. MGI(+)D(+), MGI(+)D(-), and MGI(-)D(-) mouse myeloid leukemic cells, which genetically differ in their competence to be induced to undergo normal cell differentiation in vitro by the normal macrophage- and granulocyte-inducing protein MGI, were analyzed for their ability to undergo cell differentiation in diffusion chambers in vivo. As after induction by MGI in vitro, MGI(+)D(+) clones were induced for Fc and C3 rosettes, lysozyme, and mature macrophages and granulocytes in normal syngeneic or allogeneic mice. MGI(+)D(-) clones were also induced in these mice for all these properties, although in vitro they were not induced by MGI for mature cells. The MGI(-)D(-) clones were induced in vivo for C3 and Fc rosettes, lysozyme, and intermediate stages but not for mature cells, whereas none of these properties were induced in these clones by MGI in vitro. Thus, certain types of myeloid leukemic cells differentiate better in vivo, possibly due to the presence of higher effective concentrations of MGI and/or other inducing factors, and MGI(+)D(+) and MGI(+)D(-) cells can completely differentiate in vivo to mature cells. In vivo differentiation was inhibited in mice treated with cyclophosphamide. It was also inhibited in various strains of nude mice, except for one MGI(+)D(+) clone, where it was inhibited in C57BL/6 but not in ICR nude mice. This MGI(+)D(+) clone was also the only clone that was induced to differentiate normally in vitro by a 23,000 molecular weight form of purified MGI. The results suggest that different clones respond to different molecular forms of MGI, which may be present in different proportions in some animals, that in vivo differentiation by MGI possibly with other factors may be regulated by cells involved in the immune response, and that this differentiation can be genetically controlled. Differentiation in vivo was enhanced by injection of conditioned medium containing MGI and by inoculation of MGI-producing cells, including normal granulocytes. This indicates that the induction of normal differentiation of myeloid leukemic cells in vivo can be enhanced by these treatments.


Isolation of myeloma variants with predefined variant surface immunoglobulin by cell sorting. We describe a procedure for the isolation of somatic cell variants in which gene products are expressed on the cell surface that are not expressed in the wild type. Cloned cells of the myeloma line MPC 11, which expresses an IgG2b protein, were incubated with an antiserum specific for IgGI and IgG2a. Cells reacting with this antiserum were stained with a fluorescent anti-antiserum and enriched in three cycles of sorting in the fluorescence-activated cell sorter and subsequent growth in vitro. From the enriched population two variants were isolated by cloning in soft agar. One of them expressed a variant immunoglobulin that types serologically as an IgG2a but whose variable portion was idiotypically related to that of the MPC 11 wild-type protein.


Mechanisms of trypanosome-mediated suppression of humoral immunity in mice. Spleen cells from Trypanosoma musculi-infected mice were unable to respond to sheep erythrocyte antigen in vitro; moreover, they suppressed the responses of normal spleen cell cultures in dose-dependent fashion. Suppression was maximal with spleen cells obtained during maximal parasitemia and waned as the donors recovered from infection. A macrophage-enriched population of spleen cells from infected mice, prepared either by adherence to plastic or by density gradient centrifugation, was not contaminated by the parasites and was not suppressive, whereas the plastic-nonadherent population was both contaminated and suppressive. Adherent and nonadherent cells of infected mice, separated by use of nylon wool columns, were almost equally suppressive and equally contaminated by trypanosomes. Addition of specific rabbit antiserum against T. musculi to cultures containing cells from infected mice eliminated contaminating parasites and alleviated suppression exerted by cells obtained from mice early during the course of infection but not after 12-15 days of infection. The suppression exerted by enriched T-cells obtained from mice on day 12 of infection was largely alleviated by use of the antiserum. A large portion of cells obtained on day 14 of infection could be killed by the antiserum and complement. It appeared that soluble substances derived from the parasites acted directly on B lymphocytes or essential assistant cells rather than by activating suppressor T cells or macrophages.


Role of T lymphocytes in cellular immune responses during herpes simplex virus infection in humans. Lymphocyte blast transformation and interferon production in mononuclear cell culture prepared on Ficoll-Hypaque gradients from individuals with herpes simplex virus-I infection were enhanced by a disease recurrence. Responses to both herpes simplex virus-2 and phytohemagglutinin were unaltered. Transformation to herpes simplex virus-I antigen was adversely affected by depleting either thymus-derived (T) lymphocytes or bone marrow-derived (B) lymphocytes together with monocytes from cultures. The transformation response was reconstructed when the selectively depleted lymphocyte populations were recombined. X-irradiation of either T or B lymphocytes and monocytes showed that T lymphocytes incorporated [3H]thymidine with the aid of a radioresistant non-rosetting cell, probably a monocyte. Depletion of B lymphocytes and monocytes, but not of T lymphocytes, resulted in reduction in interferon production. Irradiated B lymphocytes and monocytes failed to produce significant quantities of interferon, suggesting that a radiosensitive B cell was a major interferon source.


Catecholamine levels in the whole brain and the probability of memory formation are not related. Amnesia was induced with reserpine or was blocked with 1-dopa and 5-hydroxytrptophan before or after passive avoidance training in mice. The levels of dopamine and norepinephrine in the whole brain were measured in corresponding groups with gas chromatography-mass spectrometry. No correlation was found between retention and the levels of these catecholamines in the brain.


Chlordiazepoxide-fluoxetine interactions on food intake in free-feeding rats. Chlordiazepoxide, which blocks serotonin turnover, increased food intake; and fluoxetine, a serotonin agonist, decreased food intake. Administration of combinations of the two drugs showed an antagonistic dose-dependent relationship, implicating a satiety of hunger mechanims which is mediated by serotonin.


Transcatheter vascular occlusion therapy with isobutyl 2-cyanoacrylate (bucrylate) for control of massive upper-gastrointestinal bleeding. Transcatheter embolization with bucrylate, a tissue adhesive, was performed in 16 patients with massive upper-gastrointestinal bleeding. Control of arterial bleeding from the stomach was achieved in 6 of 8 patients, and from the duodenum in 3 of 4. Embolization of gastric veins resulted in temporary control of esophageal variceal bleeding in 3 of 4 patients. Histological study showed no evidence of bucrylate causing histotoxicity in 2 patients. Because bucrylate polymerizes rapidly, a localized vascular occlusion mimicking a surgical ligation is produced. Because collateral vessels are not occluded. localized tissue ischemia is unlikely. Tissue adhesives are, however, difficult to use.


[Postoperative digestive complications of thoracic surgery]. The authors investigated the pathologic digestive manifestations that have developed after 2000 surgical interventions in the thoracic-pulmonary field. Four categories of digestive disturbances have been considered: paresis (dynamic ileus), including acute gastric dilation; haemorrhage; mechanical ileus, and digestive perforation. The digestive pathology developed either autonomously or in association with other symptoms of shock. A total of 788 digestive complications have been recorded (39%), of which: 654 cases of dynamic ileus, 118 cases of haemorrhage, 2 cases of mechanical ileus, 4 cases of perforation and 10 cases of mixed complications. In fact haemorrhage is more frequent, haemorrhagic gastritis being found in most of the deceased patients, following prolonged postoperative evolution. The simultaneous or succesive development was noted of digestive complication and respiratory failure in a total of 126 patients (6,3% of the total number of cases investigated). Pulmonary failure became more severe after the onset of dynamic ileus, especially after acute gastric dilatation. The development of any digestive complication represented in all cases an aggravation factor, especially when accompanying respiratory failure. The decrease with time of the incidence of digestive complications, from 57% to 21,8%, is due to changes that have occured in anesthesy techniques, of which NLA appears to play the most important role.


Presence of alpha-naphthyl acetate esterase activity in human haematopoietic cell lines and in fresh biopsy specimens of lymphoma and myeloma. We have previously shown that non-proliferating human T- but not B-lymphocytes contain demonstrable amounts of acid alpha-naphthyl acetate esterase (ANAE). The usefulness of this histochemical marker for the diagnosis and classification of malignant lymphoid tumors was investigated by use of a panel of established normal and malignant human haematopoietic cell lines and fresh biopsy cells from malignant lymphomas and myelomas. The results showed that not only the T-cell derived acute leukaemia lines, but also histiocytic lymphoma and myeloma lines and some of the lymphoma (Burkitt and lymphocytic) and non-neoplastic lymphoblastoid cell lines with B-cell surface markers expressed strong ANAE reactivity. Some but not all of the immunoglobulin producing myeloma and lymphocytic lymphoma biopsies were ANAE-positive. Inhibition experiments with sodium fluoride and E-600 demonstrated that although the T-lymphocyte specific esterase is predominantly of 'A'-type, the malignant lines contain also non-specific 'B' esterase and pseudocholinesterase. As the presence of the various esterases did not demonstrate any specific distribution pattern among he haematopoietic cell lines of different origin, we concluded that the ANAE marker is no longer T-specific when malignant lymphoid cells are considered, and that the usefulness of this marker in routine diagnostic work therefore is limited.


Intravaginal electrical stimulation. Clinical experiments of urethral closure. The effect on the urethra of intravaginal electrical stimulation (IVS) was registered by means of urethral pressure profiles (UPP). With the object of finding the most appropriate electrical parameters and optimal electrode positions within the vagina, 24 patients with stress incontinence, 22 with urgency and 4 continent women were studied. Electrical stimulation was given via an obturator with seven electrodes, which could be connected in different combinations of pairs. In all the women, stimulation with the electrodes in specific positions effected a more marked rise in the UPPs than with the electrodes in other positions. A change in position of more than 5 to 10 mm caused a decrease in the response. It was determined that a frequency of between 20 to 50 Hz with a pulse duration of 1 to 5 ms was most effective for urethral closure.


Intravaginal electrical stimulation. Clinical experiments on bladder inhibition. The effect of intravaginal electrical stimulation (IVS) on the bladder in 17 patients with motor detrusor instability was explored. Isotonic volume registrations and cystometries were used for evaluation of volume increase and inhibition of abortive detrusor contractions. With either one or the other method, bladder inhibition was found in all patients, but with both methods only in 6. During isotonic volume registration, the volume increase showed considerable variations ranging between 4 to 465%, and during cystometry between 11 to 3500%. Bladder inhibition proved to be most effective when using a frequency of 10 Hz.


Mechanisms for closure of the human urethra during intravaginal electrical stimulation. The effect of intravaginal electrical stimulation (IVS) on the urethral pressure profile (UPP) before and during succinylcholine blockade or spinal anaesthesia was studied in patients with stress incontinence and in patients with clinically normal urethral function. During succinylcholine blockade, the UPP was lowered to 74% and during spinal anaesthesia to 39% of the original maximal UPP. IVS could not influence the UPP during succinylcholine blockade, while the UPP could be restored during spinal anaesthesia when the stimulation strength was increased 3 to 4 times. The following conclusions were arrived at: 1) The urethral effect of IVS is due to activation of somatic nerves and not to activation of nerves supplying smooth muscles or direct activation of striated and smooth muscles. 2) The more pronounced depression of the UPP during spinal anaesthesia compared to succinylcholine blockade should be caused by the loss of nervous activity of the smooth muscles. 3) The fact that the UPP could be restored during spinal anaesthesia indicates that activation of somatic efferents can compensate for the loss of striated and smooth muscle activity. Therefore, IVS can control incontinence in partial lower motor neuron lesions, provided a sufficient number of efferent neurons are preserved.


Long-term intravaginal electrical stimulation in urge and stress incontinence. Using a new device for intravaginal electrical stimulation (IVS), 24 women with pure stress incontinence, mixed urge and stress incontinence or urge incontinence due to detrusor instability, were treated. To minimize mechanical discomfort, the electrode carrier was made of flexible material and inflatable. Furthermore, this design facilitated fixed, constant positioning of the electrodes at individually tested sites to produce maximum response at voltage well tolerated by the patient. The stimulation frequency was adjusted to suit the cause of incontinence: 20 to 50 Hz in stress incontinence, 10 Hz detrusor instability. The electrode carrier was well accepted. Seven of the 9 patients with pure stress incontinence became continent during IVS. Three of them have so far remained continent for 2 to 8 months without IVS. The 15 patients with detrusor instability or mixed incontinence were all free from symptoms after IVS for more than 3 months. Two of them have remained cured for more than 3 months after they had stopped IVS.


A new fatal complication of transtracheal aspiration. A new, fatal complication of transtracheal aspiration is described in a cirrhotic patient. Death was related to gastrointestinal bleeding (rupture of oesophageal varices and Mallory-Weiss syndrome) due to unrestrainable coughing originating from transtracheal aspiration.


[Acute "high risk" and "low risk" juvenile lymphatic leukemia (proceedings)]. After an initial blood and thorax examination, 97 children with ALL were divided into "high risk" and "low risk" groups. From the 20 new "high risk" patients seen between 1972 and 1975 about one quarter were still alive 3 years later, the corresponding proportion from 37 "low risk" patients being about two thirds. Despite increased therapy, the number of early relapses does not appear to have decreased in the new "high risk" cases seen between 1976/77. An investigation of cell surface markers established that T-ALL always occurred in the "high risk" group, whereas B-negative/T-negative ALL was found not only in the "low risk" group but also occasionally in the "high risk" group.


alpha1-Antitrypsin: the presence of excess mannose in the Z variant isolated from liver. The Z variant of alpha1-antitrypsin was isolated by a new technique from the liver of a patient homozygous for the Z allele of the protease inhibitor locus. The material was homogenous and antigenically competent but had no protease inhibiting capacity. An interesting correlation was found between the subcellular localization and the carbohydrate composition of the Z variant from liver. Carbohydate analysis of this glycoprotein showed an absence of galactose and sialic acid, an appreciable decrease in N-acetylglucosamine, and an almost twofold increase in mannose residues. These data indicate a considerable slowdown in the processing of the oligosaccharides of liver Z variant. In spite of the absence of sialyl residues, the liver Z varant was microheterogeneous by analytical isoelectric focusing. The isoproteins of liver Z variant coincided with those of asialo M variant in the focusing field.


Impulse blockade in frog cardiac ganglion does not resemble partial denervation in changing synaptic organization. Partial denervation of parasympathetic neurons in the frog heart by surgical section of one vagus nerve results in a marked reorganization of functional synaptic connections made by the remaining vagus nerve. These changes are not simply due to a lack of impulse activity per se in the sectioned nerve because blockage of impulses in one vagus with tetrodotoxin-impregnated cuffs did not cause similar changes in the innervation pattern of the ganglion. Furthermore, tetrodotoxin-blocked vagal fibers retain their ability to sprout and can form new synapses on denervated neurons.


Tumor-promoting phorbol esters inhibit binding of epidermal growth factor to cellular receptors. Tumor-promoting phorbol esters and related plant macrocyclic diterpenes inhibit the binding of epidermal growth factor to its receptors on HeLa cells. This effect shows marked structural specificity and correlates with other biological effects of these compounds on mouse skin and in cell culture systems. The active compounds inhibited binding of 125I-labeled epidermal growth factor with a 50 per-cent effective dose in the range of 10(-8) to 10(-9) M. Inhibition appears to be due to a decrease in the number of available epidermal growth factor receptors rather than a change in receptor affinity. These results suggest that certain biologic effects of tumor promoters may result from alterations in the function of cell surface receptors involved in growth regulation.


Osteosarcoma--the winds of change.

Osteosarcoma--the winds of change. The occurrence of pulmonary metastases in patients suffering from primary classic osteogenic sarcoma is compared among two groups of patients treated according to different protocols at Groote Schuur Hospital. A group of 28 patients treated by radiation and delayed amputation (before the end of 1974) is compared with 12 patients managed by immediate ablation and adjuvant chemotherapy with vincristine, high-dose methotrexate and leucovorin rescue, and adriamycin (after 1974). The incidence of pulmonary metastases at 12 months was significantly lower in the latter group.


Cystic fibrosis in Southern Africa. Including the preparation of a register of carriers and potential carriers. Little has been published on cystic fibrosis (CF) in Whites in southern Africa, and no figures as to incidence exist. A register of CF patients, their parents (obligatory carriers), siblings, uncles, aunts and first cousins (potential carriers) has been compiled for southern Africa. The degree of co-operation shown by colleagues and by families whose addresses have been provided by them, and possible reasons for non-co-operation are discussed. From the numbers and birth dates of patients a rough estimate of the incidence in the Republic of South Africa, South West Africa and Rhodesia has been made. In all three regions, but especially in South Africa, incidence is likely to have been underestimated. Details available from the register include the number of CF patients alive and dead, those who presented with meconium ileus, the number of affected patients per family, consanguinity among the parents or grandparents, the frequency with which identical surnames were encountered, and the sibship sizes of all those on the register. Towns and districts with a population rich in the CF gene are mentioned. The number of potential carriers has been determined, so that they can be screened when a practicable detection test is devised. The register has answered a number of questions about CF in southern Africa. It has focused attention on the disease in the region and played a major catalytic role in the formation of the Southern African Cystic Fibrosis Association.


Upper gastrointestinal hemorrhage: aggressive management decreases mortality. In a retrospective study of 630 patients with upper gastrointestinal hemorrhage admitted to the Royal Victoria Hospital between 1963 and 1971, the overall mortality was 12.54%. Mortality increased in patients receiving more than 10 units of blood and in patients over 60 years of age. Mortality decreased in patients in whom the site of hemorrhage was known prior to operation. Early surgery for gastric ulcers and conservative therapy for acute gastric erosions reduced mortality. Therefore in 334 patients admitted to the Royal Victoria Hospital between 1973 and 1976 with upper gastrointestinal hemorrhage, an aggressive approach to diagnosis and management was emphasized. There was a significant decrease in patients with duodenal ulcers, acute gastric erosions, and gastric ulcers who received more than 10 units of blood. There was a significant increase in the use of endoscopy to establish the source of hemorrhage and a significant increase in the use of endoscopy to establish the source of hemorrhage and a significant decrease in the number of patients who did not have a diagnosis prior to operation. There was also a significant increase in early surgery for gastric ulcers. This regimen led to a significant decrease in mortality (6.69% vs. 12.54%). This report demonstrates that early diagnosis and management based on the lesion found reduces mortality from upper gastrointestinal hemorrhage.