Regulation of antibody response in vitro. IX. Induction of secondary anti-hapten IgG antibody response by anti-immunoglobulin and enhancing soluble factor. Attempts were made to induce antibody response of hapten-primed cells by stimulation with anti-immunoglobulin (Ig) antibody and cellfree supernatant (CFS) which contained nonspecific enhancing factor. Mesenteric lymph node cells were obtained from rabbits which were primed with dinitrophenylated ragweed antigen (DNP-Rag), and the primed cells were incubated in vitro with either anti-rabbit gamma-chain or anti-Fab antibody for 24 hr. After washing, the cells were cultured in CFS which was obtained from the culture of DNP-Ascaris (DNP-Asc)-primed lymph node cells with free carrier (Asc). The results showed that hapten-primed cells were triggered for IgG anti-DNP antibody response by the two reagents, i.e., anti-Ig antibody and CFS, both which did not share any antigenic specificity with the priming antigen (DNP-Rag). Neither anti-Ig alone nor CFS alone induced anti-hapten antibody response. Anti-Ig and CFS triggered not only hapten-primed B cells but also the other IgG-bearing (B) cells for IgG synthesis. Lymph node cells of umprimed animals were activated for IgG synthesis by the stimulation with anti-Ig followed by culture in CFS. Evidence was obtained that anti-Ig antibody has to be divalent for the activation of B cells. Stimulation of DNP-primed cells with the F(ab')2 fragment of the antibody and CFS-induced anti-hapten antibody response, whereas the Fag' fragment of the anti-Ig plus CFS failed to do so. The results suggested that bridging of cell-surface Ig receptors by multivalent ligand is the initial step of B cell activation. Another evidence for the activation of hapten-primed B cells by anti-Ig was obtained by supplemental immunization of DNP-Asc-primed animals with the Fc fragment of goat IgG. Stimulation of mesenteric lymph node cells from these animals with goat anti-rabbit-Ig alone (no CFS) resulted in the formation of anti-DNP IgG antibody. The results indicated that lymphocytes primed for goat IgG collaborated with DNP-primed IgG-B cells when the lymph node cells were stimulated with goat anti-Ig.


Thymus-independent antigens: the preparation of covalent, hapten-ficoll conjugates. A general approach is presented for covalently attaching carboxyl and primary amino groups to Ficoll and other high molecular weight polysaccharides in a readily controlled manner. The polysaccharides are omicron-carboxymethylated with chloroacetate in NaOH solutions. Amino groups are next introduced by monoamide formation with ethylenediamine using a water-soluble carbodiimide. Reactions are carried out in aqueous solutions; excess reactants and by-products are removed by dialysis. Three different ways for coupling the 2,4-dinitrophenyl hapten to the amino derivative of Ficoll are described. Preliminary evidence indicates that 2,4-dinitrophenyl-Ficolls, prepared by procedures developed in this study, are potent thymus-independent antigens which can specifically stimulate B cells both in vivo and in vitro. Hapten-Ficoll conjugates should be exceptionally useful for studies of B lymphocyte activation because of the ready availability of the starting material and the ease with which a wide variety of hapten derivatives may be prepared.


Characterization of the lymphocyte surface receptors for Con A and PHA. Human peripheral blood lymphocytes were iodinated by the lactoperoxidase technique, and the surface receptors for the mitogens concanavalin A (Con A) and phytohemagglutinin (PHA) were analyzed by solubilizing the membrane protein and incubating with mitogen and antimitigen antibody. The resulting precipitates were washed and analyzed by gel electrophoresis. Con A was to bind to about twice as much labeled protein as PHA. Sodium dodecyl sulfate gels showed that multiple surface membrane proteins bind to these mitogens and that the pattern of peaks of Con A receptors in generally similar to the pattern of PHA receptors. Long-term lymphoid tissue culture cells lines also show multiple receptor peaks for mitogens, indicating that the heterogeneity of receptors is not caused entirely by lymphocyte heterogeneity.


The stimulation of immunoglobulin production in murine spleen cells by the pokeweed mitogens. We have shown that of the five mitogens purified from the salt extracts of pokeweed, only Pa-1, the B cell mitogen, has the ability to stimulate immunoglobulin production in murine B cells in the absence of classical T cells. Furthermore, the T cell mitogens (Pa-2-Pa-5) not only are unable to stimulate DNA or immunoglobulin synthesis by B cells in the absence of T cells, but cannot stimulate immunoglobulin production by B cells even in the presence of T cells. This suggests that Pa-2-Pa-5 do not stimulate adequate helper function in T cells or that if such a helper function is stimulated, an additional stimulatory factor is required for immunoglobulin production, which is not provided for by Pa-2-Pa-5.


Interaction of plant lectins with purified human lymphocyte populations: binding characteristics and kinetics of proliferation. With six purified plant lectins as probes of cell surface structure, human T, B, and Null lymphocytes have been examined for cell surface differences. The results of binding experiments with radioiodinated lectins indicate that these three lymphocyte populations, although functionally different, bind equivalent amounts of E- and L-PHA, lentil PHA, Con A, RCA-I, and WGA. Since these lectins are capable of binding to at least four different cell surface oligosaccharides, these data indicate that human T, B, and Null lymphocytes do not differ with respect to surface content of these carbohydrate structures. In addition, all six lectins were investigated for their ability to stimulate DNA synthesis in these human lymphocyte populations. Four of these lectins (E- and L-PHA, lentil PHA, and Con A) were mitogenic for human lymphocytes, whereas RCA-I and WGA failed to stimulate significant DNA synthesis in any lymphocyte population. When incubated with the mitogenic lectins, both B and Null cells displayed a delayed peak of DNA synthesis in comparison to T cells. Thus, despite virtually identical binding characteristics, the lectin-induced mitogenic response exhibited by B and Null cells was markedly different kinetically from that of T cells.


Quantitative and immunologic aspects of the handling of 2,4 dinitrophenyl guinea pig albumin by macrophages. Studies correlating quantitative aspects of the handling of dinitrophenyl guinea pig albumin (DNP-GPA) by guinea pig macrophages with the potential of cell-associated antigen to initiate proliferation of immune T lymphocytes have examined the nature of immunologically relevant antigen. After the loss of 75% of cell-bound DNP-GPA during the first 24 hr of in vitro culture, the remaining antigen persists qualitatively unchanged throughout further culture. However, coincident immunogenicity of the macrophage-associated NDP-GPA progressively deccreases, suggesting loss of accessibility of the antigen to responding immune lymphocytes. There is a small, stable, surface antigen pool but these studies suggest that the immunologically critical fraction of DNP-GPA, as regards guinea pig T cell activation, is resistant to trypsinization and inaccessible to antibody.


Alkaline phosphatase in differentiating guinea pid thymocytes: an ultracytochemical study. Alkaline phosphatase (AP) was demonstrated ultracytochemically on the cell membrane of guinea pig thymocytes. AP usually covers the whole cell surface. In a small subpopulation of thymocytes the cell membrane is totally AP-negative. These cells are located by light microscopy in the thymic medulla and have been shown previously to possess the migratory properties of mature thymocytes. This AP-negative subpopulation most probably represents the T cell population in the thymic medulla. No distinct morphologic differences could be observed between these AP-positive and AP-negative thymocytes. Additionally, a small AP-negative cell population with characteristics of immature lymphoid cells was noted. These lymphoid cells, which are seen more numerously in the fetal thymus, might represent the differentiating stem cells in the guinea pig thymus.


Release of mitogenic factor by mouse lymph node cells stimulated with PHA in vitro. Inhibition of this phenomenon by the addition of thymocytes. Thymidine uptakes of mouse lymph node cells and thymocytes in response to phytomitogen lectins were investigated in vitro. It was observed that mixtures of lymph node cells and thymocytes yielded higher 3H-TdR incorporations than expected when exposed to concanavalin A (Con A) or pokeweed mitogen (PWM), but lower incorporations than anticipated with phytohemagglutinin (PHA) as a stimulant. The observed enhancement of the response could be explained by factors which are stimulatory for thymocytes released by the lymph node cells. However, such mitogenic factors (MF) were released not only by Con A and PWM exposed cells but also by PHA expose lymph node cells. Further experiments showed that the admixture of thymocytes inhibited the release of MF by lymph node cells exposed to PHA but not to Con A or PWM. Since medullary thymocytes did not exhibit any inhibitory activity, it is likely that cortical thymocytes are responsible for this effect. The mechanism by which thymocytes inhibit MF production of lymph node cells exposed to PHA is not clear. MF was efficiently produced by lymph node cells cultured with PHA in "thymocyte-conditioned" medium and the MF activity was only marginally decreased by absorption with thymocytes. The results are discussed in the light of recent findings showing that thymocytes may both enhance and depress the immune response of other lymphocytes.


Characterization of mouse cells releasing or responding to mitogenic factor induced by phytomitogens in vitro. Mouse lymphocyte populations exposed to mitogen were tested for their capacity to release factors that stimulate other lymphocytes to synthesize DNA or enhance their response to mitogens in vitro. The target lymphocyte for this mitogenic factor(s) (MF) was also characterized. The results showed that lymph node and spleen cells release more MF than thymocytes upon exposure to Con A, PHA or PWM in vitro. The T cells were found to be largely responsible for MF production, since cell suspensions depleted of phagocytic cells did not exhibit any decreased ability to produce MF and spleen cells from congenitally athymic (nude) mice produced no detectable MF activity. The MF stimulated thymocytes, lymph node cells, and spleen cells to synthesize DNA. Spleen cells from nude mice were also stimulated. The MF released by lymphocytes in response to Con A was found to induce DNA synthesis of lymphocytes in itself and did not require the presence of mitogen. It is concluded that phytomitogen lectins stimulate T cells to synthesize DNA and to release soluble factor(s) which are mitogenic for both T and B cells. The latter cells may thus be unresponsive to the phytomitogen, but still undergo blast transformation.


Complications of free grafts of masticatory mucosa. A discussion has been presented and examples provided to illustrate some of the complications that may be encountered in conjunction with free grafts of masticatory mucosa. The clinical problems presented are seen infrequently, but the clinician must be aware of the possibility of their occurrence when counseling patients on the possible sequelae of such surgical procedures. A knowledge of complications that may occur in free soft tissue grafting procedures, and of the underlying mechanisms causing these problems, may aid the clinician in anticipating and avoiding similar experiences.


Effects of prenylamine on cardiac membrane currents and contractility. The influence of prenylamine on the electrical and mechanical activity of frog atrial muscle fibers has been studied under voltage clamp conditions. At a concentration of 10-4 M, prenylamine blocks the action potential without much affecting the resting potential. The drug depresses the peak transient sodium conductance with a dissociation constant of 1.7 times 10-5 M and on a one-to-one stoichiometric basis. The curve relating peak sodium conductance to membrane potential is slightly shifted in the direction of hyperpolarization. The time to peak sodium current and the rate of sodium inactivation are not significantly altered. With 2 times 10-5 M prenylamine, the steady-state sodium inactivation curve is shifted by 5 mV to more negative membrane potentials but the decreased availability of the sodium system at the resting level is not sufficient to account for the reduction of sodium current. Recovery from sodium inactivation upon repolarization is distinctly slowed. The slow (secondary) inward current carried by calcium and/or sodium and the steady-state outward current are also depressed by prenylamine. The phasic (twitch-like) contraction related to the slow inward current is slightly decreased. The tonic (sustained) contraction associated with long-lasting depolarizations is increased and the time course of relaxation is retarded by prenylamine.


Light scattering associated with tension changes in the short-range elastic component of resting frog's muscle. 1. A study has been made of some optical and associated mechanical properties of resting frog's sartorius muscles in isotonic and hypertonic solutions. Tension and transparency changes accompanying small alterations of muscle length (smaller than 1-5%) were recorded simultaneously. 2. The form of the transparency change is complex. It has three phases, two of which occur during the length change and the third (delayed phase) after it is complete. Directional recording of the response reveals both scattering and diffraction components. 3. The change of light scattering is associated with tension changes in the short-range elastic component (SREC) of the muscle. Its magnitude is related to the stiffness of the SREC; both increase when the osmotic strength of the external solution is raised and when muscle length is increased. 4. The change of light scattering is not much affected by the velocity of the applied length change. This is true also of the mechanical stiffness of the SREC. 5. The origin of the diffraction change is not known. 6. It is concluded that the scattering effect is caused by conformational changes in the SREC.


Homologs of dopa, alpha-methyldopa, and dopamine as potential cardiovascular drugs. Starting from 3,4-dimethoxyphenacyl bromide, 2-amino-4-(3,4-dihydroxyphenyl)butyric acid (homodopa) was synthesized in six steps. 5-Hydroxyhomodopa was similarly prepared. alpha-Methylhomodopa was synthesized in four steps from zingerone [4-(4-hydroxy-3-methoxyphenyl)-2-butanone]. alpha-Methylhomodopa showed no antihypertensive activity in the genetic hypertensive rat. Homodopa did not potentiate the behavioral effect of Dopa or inhibit Dopa decarboxylase. Homodopamine, unlike dopamine, did not increase renal blood flow in the dog.


In vitro studies of axillary lymph node cells in patients with breast cancer. A total of 170 axillary lymph nodes were obtained from fresh mastectomy specimens from 81 women with breast cancer. Lymph node cells were tested in vitro for T and B cells by the rosette technique and immunofluorescence microscopy and for functional capacity by response to the mitogens phytohemagglutinin (PHA) and concanavalin A. T cells showed a wide range of relative values: 32-80 percent, with a mean of 63.5 percent. B cells defined by the presence of surface immunoglobulins ranged from 14 to 61 percent (mean, 35.8 percent); those defined by the presence of C3 receptors, from 8 to 54 percent (mean, 24.9 percent); and those defined by the presence of IgG-specific (Fc) receptors, from 10 to 45 percent (mean, 27.5 percent). Cells with the C3 and Fc receptors constituted approximately two-thirds of the cells not binding spontaneously to sheep red blood cells (non-SRBC-R), whereas virtually all non-SRBC-R stained for surface immunoglobulins. The proportion of T and B cells and the response to mitogens varied widely among nodes and among patients. Differences were significant between values observed in young and old patients, nodes with and those without metastatic disease, and lymph nodes with different morphology. Lymph nodes from patients over 60 years old showed a higher proportion of B cells and a lower proportion of T cells than did those from patients 45 years of age or younger. Lymph nodes with disease metastic to them also showed a higher percent of B cells and a lower percent of T cells than the nodes that did not have metastatic disease. Lymph nodes with lymphocyte predominance showed a relatively high proportion of T lymphocytes, a high PHA response, and a low content of B lymphocytes. By contrast, lymph nodes with germinal-center predominance showed a relatively low content of T cells, a low PHA response, and a relatively high proportion of B lymphocytes.


Immunogenetics of a thymus antigen in lymphoma-prone and lymphoma-resistant colonies of wild mice. The Thy-1 (theta) antigen was identified in wild mice (Mus musculus), the frequency of its alleles was determined in two natural populations of wild mice, and the possible T-cell origin of spontaneous lymphomas was investigated in one of these populations. Reaction patterns for Thy-1 antigen with the use of direct cytoxicity and indirect absorption assays were identical in wild mice and inbred strains. Between 15 and 55 percent of viable spleen cells from healthy young or old wild mice were Thy-1 positive. Spleen, but not brain, cells from older wild mice were less strongly positive. Wild mice from the lymphoma-prone population were polymorphic for Thy-1alpha and Thy-1beta alleles, whereas wild mice from the lymphoma-resistant populations were homozygous for the Thy-1beta allele. Contrary to expectation, a higher frequency of the Thy-1beta allele was noted in the mice with lymphomas. Alleles at two other loci on chromosome number 9 (Mod-1alpha and Trfbeta) were fixed in both populations. The absence of detectable Thy-1 antigen on spleen cells (despite its detectability in undiminished titer in brain tissue) in 80 percent of mice with lymphomas, along with the absence of thymus involvement in the lymphomatous proliferations, suggested that these tumors are derived from an expansion of non-thymus-derived cells.


Acute duodenitis and duodenal ulceration after burns. Clinical and pathological characteristics. The clinical and pathological characteristics of Curling ulcer were defined by early and serial endoscopic examination of the duodenum in 37 burned patients. Duodenal disease was present in 27 patients and occurred only in patients with burns involving more than 38 percent of the total body surface. Erosive "duodenitis" could occur within 12 hours after injury and was usually associated with acute gastric disease. Isolated duodenitis occurred only in patients with pancreatitis. Contrast roentgenograms did not reliably show the superficial mucosal disease. Duodenal ulcerations were present in 12 patients and developed on a background of diffuse superficial mucosal injury. Other complications in the patient's postburn course influenced disease progression. Hemorrhage occurred in six patients with duodenal disease, usually originating from a posterior duodenal ulcer. Uncomplicated ulcers invariably healed within five weeks after diagnosis.


Angina during hemodialysis. Treatment by coronary bypass graft. In a 52-year-old man with chronic renal failure, severe angina occured when he was receiving hemodialysis. A double coronary bypass graft was performed, providing complete relief.


Use of blood component therapy for gastrointestinal bleeding in patients with cirrhosis of the liver. A prospective study was designed to compare the administration of available fresh blood and component therapy in the treatment of gastrointestinal bleeding in patients with cirrhosis of the liver. Fifty bleeding cirrhotic patients were randomly assigned to treatment: 17 patients recieved 51 percent fresh blood (Group 1), 16 patients received 22 percent fresh blood (Group 2), and 17 patients received 25 percent component therapy consisting of packed cells, fresh frozen plasma, and platelet concentrate (Group 3).  The mortality rate was unaffected by the type of blood replacement.  Neither the blood replacement requirement (Group 1:51 plus or minus 0.9 units Group 2:5.5 plus or minus 0.8 units, Group 3:7.1 plus or minus 1.1 units) nor the duration of bleeding (Group 1:39 plus or minus 0.8 days, Group 2:6.3 plus or minus 2.4 days, Groups 3:5.8 plus or minus 1.0 days) were significantly different.  There was no correlation between the mean age of blood or plasma received and the units of blood replaced or the duration of bleeding.  Patients with severe coagulation abnormalties had a significantly increased mortality.  Component therapy was as effective as the fresh blood regimen in cirrhotic patients with acute gastrintestinal hemorrhage.


[Effect of an increased content of oxygen and carbon dioxide on vestibular resistance]. Forty-two experiments on 21 test subjects, aged 20 to 40, were carried out to study possibilities of increasing vestibular resistance. This was achieved by improving the cerebral blood supply of the subjects who used the breathing air of 40-43% oxygen, 2% carbon dioxide and nitrogen. The results were treated statistically. This breathing air proved to increase the resistance of the vestibular analyzer to adequate stimuli. It is recommended to use this breathing air consisting of 40-43% oxygen, 2% carbon dioxide and nitrogen to prevent motion sickness and to discontinue vestibulo-vegetative disturbances that may appear in people using different flying and ground vehicles.


Early cellular responses to mitogens and adjuvants in the mouse spleen. The purpose of this study was to evaluate the cellular events in the spleens of mice following the intravenous injection of mitogens and adjuvants. The compounds used were concanavalin A, polyadenylic polyuridylic acid, beryllium sulfate, bacterial endotoxin, tuberculin-purified protein derivative, and dextran sulfate. Nine different strains of mice (some deficient in the C5 component of complement) received a single dose of these compounds, and their spleens were studied at sequential time intervals, ranging from 1 hour to 14 days. Concanavalin A triggered marked blast activity in the T cell zones of the splenic white pulp which was maximal at 24 hours following the injection. -3H-thymidine incorporation increased significantly, but the number of immunoglobulin-negative cells did not increase, probably because of a concomitant loss of hematopoietic cells. Polyadenylic polyuridylic acid and beryllium sulfate produced an increase in the number of lymphocytes in the T cell zones by 12 to 24 hours, but mitotic activity was unremarkable. None of the above T cell zone changes was observed in neonatally thymectomized mice. Endotoxin, purified protein derivative, and dextran sulfate produced marked B cell zone hyperplasia. Similar histologic changes were seen in the thymectomized animals. -3H-thymidine incorporation and number of immunoglobulin-positive cells were significantly increased by 24 hours. Endotoxin and dextran sulfate in some strains of mice caused marked depletion of the T cell zones. The effects of concanavalin A, endotoxin, and dextran sulfate were unrelated to the presence or absence of C5 protein. These experiments show that (1) concanavalin A, bacterial endotoxin, tuberulin-purified protein derivative, and dextran sulfate trigger in vivo the same cellular components of the immune system as they do in vitro; (2) polyadenylic polyuridylic acid and beryllium sulfate may influence the immune system by increased localization of lymphocytes in the T cell zones.


Deoxyribonucleic acid synthetic response of mouse lymphoid cells in microculture with T-lymphocyte-dependent mitogens. Various numbers of mouse thymus, lymph node, or spleen cells were cultured in serum-containing medium with concentrations of 0.06 to 64 mug. per ml. of concanavalin A (Con A), using our version of the microculture technique. Maximal DNA synthetic responses were obtained with 1.0 million thymocytes (highest number used) at 4 mug. per ml. of Con A and with 0.75 million lymph node cells or 0.5 million spleen cells at 1 mug. per ml. of Con A. At optimal Con A concentration the magnitudes of response of 0.25 million thymus, compared with the same number of lymph node cells, were very similar. However, the response of lymph node cells was superior to that of thymocytes when 0.5 million initial cells were used, whereas 1.0 million thymocytes gave a better response than did the same number of lymph node cells. Regardless of the cell concentration, a comparison of responses by the three different cell types with the same cell number showed that the Con A concentration-DNA synthetic response curve was broadest for spleen cells, narrow for thymus cells, and intermediate for lymph node cells. Results in replicate experiments were highly reproducible, and the data indicated that peak DNA synthetic responses were not directly proportional to cell number when certain numbers of cells were used; the actual proportionality of response to cell number varied with the cell type and the mitogen concentration. When examined throughout the culture period, concentrations of Con A which were above the optimal for stimulation of DNA synthesis resulted in significant decreases in the number of viable cells. Time course experiments with Con A (or phytohemagglutinin)-stimulated BALB/c spleen cells showed that the initiation of DNA synthesis occurred between 12 and 24 hours of culture, with peak levels of 3H-thymidine incorporation occurring during the 2nd and 3rd days of culture. The presence or absence of fetal calf serum had essentially no effect on the Con A- or phytohemagglutinin-stimulated DNA synthetic responses during the 3rd day of culture. These results demonstrate that detailed evaluation of culture variables and mitogen concentrations is required for the most meaningful use of mitogen-stimulated DNA synthesis as a parameter for comparing different lymphoid cell populations.


[Functional state of the vestibular analyzer during lower body negative pressure tests]. With the aid of the caloric test the functional state of the vestibular analyzer of nine male athletes was investigated during their exposure to lower body negative pressure tests. The prolongation of the latent period of the caloric nystagmus and vertigo, shortening of the time of the nystagmus and vertigo were observed. It is concluded that the cerebral blood supply plays a major role in the development of vestibular reflexes.


[Ocular complications in ophthalmic zoster (author's transl)]. Ocular complications occur in about 50% of cases of ophthalmic zoster. They include inflammatory reactions of the eyelid, conjunctivitis, scleritis, keratitis, iridocyclitis, secondary glaucoma, optic neuritis, internal ophthalmoplegia, ocular motor palsies and exophthalmos. Very dangerous complications are a concomitant facial paralysis and a neuroparalytic keratitis. Then a tarsorrhaphy should be done in time. An ophthalmologist should be consulted, when the side of the tip of the nose presents vesicles (Hutchinson's rule).


The effect of various putative neurotransmitters on the release of corticotrophin releasing hormone from the hypothalamus of the rat in vitro. I. The effect of acetylcholine and noradrenaline. The effect of various putative neurotransmitters upon the release of corticotrophin releasing hormone (CRH) was investigated using the hypothalamus of the rat in vitro. Acetylcholine (1-5 pg) caused a dose-dependent release of CRH which was antagonized by hexamethonium (1-10ng) and partially antagonized by atropine (300 pg). Neither noradrenaline, dopamine nor histamine had any effect on the basal secretion of CRH. Noradrenaline (10 ng), however, was able to inhibit the release of CRH in response to acetylcholine (3 pg) and this action of noradrenaline was reduced by phentolamine (100 ng), an alpha adrenergic blocking agent.


Postpartum hemorrhage and reevaluation of uterine packing. Postpartum hemorrhage, occurring in 153 patients, is categorized according to etiology, predisposing conditions, and severity. Ruptured uterus is considered as a cause of postpartum hemorrhage, with an incidence of 7.1% overall and 11.9% in patients with severe hemorrhage. The effectiveness and complications of the uterine pack, used in 33 patients, are evaluated.


[Traumatic thrombosis of cerebral arteries]. The authors report 4 cases of angiographically diagnosed traumatic thromboses of cerebral arteries. In two of them thrombosis of the middle cerebral artery was present and in one of them it was confirmed on autopsy. In one case thrombosis involved the basilar artery and in another the subcallosal artery. The time between the injury and development of neurological manifestations was from several hours to several weeks. Major disturbances of consciousness at the time of onset of focal central nervous system lesion were never observed. Attention is called to the necessity of differential diagnosis of these conditions against traumatic haematoma. In the light of pertinent literature the problems of diagnosis, treatment and pathogenesis of traumatic cerebral arterial thrombosis are discussed.


Roentgenographic evaluation of infant and childhood trauma. The roentgenographic evaluation of the traumatized child must be appropriate for the injuries present. In the acute phase emergency screening roentgenograms tailored to the type of trauma being investigated are performed. Detailed evaluation and special studies are performed when indicated. In some instances these examinations are needed on an emergency basis; in other cases a more leisurely study can be performed when the patient's condition improves.


Spike frequency of the nodal membrane generated by high-frequency alternating current. Changes in membrane potential of single frog motor nerve fibres due to alternating current (ac) between 4 kHz and 20 kHz were recorded in the air gap equipment under constant current conditions at 20 degrees C. The experimental findings were compared with the results of computations on the basis of potential clamp data. Ac shifted mean membrane potential (averaged for every ac period) in the direction of depolarization. The mean depolarization Vm depended on current strength I; it disappeared when the sodium permeability was blocked, in the experiments by tetrodotoxin. In a current range between about 1 and 3 fold threshold strength the ac initiated repetitive activity with response frequencies v between averaged 120 Hz and 820 Hz or in the computations even higher; v depended logarithimically on current strength, but was independent of ac frequency. Elimination of current amplitude I from the nonlinear realtions v(I)  and Vm(I) led to a linear function between v and Vm. Both v and Vm depended markedly on prepolarization of the node. The results were attributed to the preferred activation of the sodium permeability under maintained high frequency ac stimulation. Differences between computations and constant current experiments occurred for very long stimulus duration when rhythmical discharges died out in the experiment.


Eye, head and body movements of the guinea pig in response to optokinetic stimulation and sinusoidal oscillation in yaw. Reflex head and eye movements were observed in the guinea pig subjected to optokinetic stimulation and whole body oscillation in the yaw axis. Optokinetic stimuli induced low velocity head movements in the direction of the stimulus with stepwise movements in the opposite direction. With motion stimuli, the head was well stabilized in space and moved to new positions in stepwise manner; in the absence of vision the head was not able to maintain a stable position. The onset of a stepwise head movement was always synchronized with a saccadic eye movement in the same direction, the coordination being similar to voluntary movement. During good head stabilization, vestibular-ocular nystagmus did not occur. The guinea pig appears to avoid nystagmus by stabilizing its head preferentially. It is likely that the vestibular ocular reflex compensates for head displacement with unity gain in the frequency range of voluntary and stepwise reflex head movement and that a close relationship exists between the control of saccadic eye movements and that of voluntary or reflex head movement.


Studies on the thymic dependence of the immunoglobulin classes of the mouse (38570). The influence of the thymus on serum immunoglobin (Ig) concentration was studied by a comparison of serum Ig levels in congenitally athymic (nu/nu) mice versus control littermate heterozygotes and adult thymectomized, irradiated, bone marrow reconsituted mice (ATx plus B) versus adult thymectomized, irradiated mice reconstituted with bone marrow and thymus (ATx plus BT). IN THE FORMER GROUP IgGl.  IgA, and IgG2a were 8%, 17% and 31% of controls.  IgM levels were increased (340%) compared to controls.  When ATx plus B mice were compared to controls.  When ATx plus B mice were compared with nonirradiated controls sigificant depressions were noted in serum IbGl and IgM.  The only significant decrease in serum Ig levels between ATx plus B and ATx plus BT was in IgGl.  These results are discussed in terms of the effects of thymic influence, residual T lymphocyte population differences between the two groups, and the effect of irradiation.


Potentiation of the L-5-hydroxytryptophan-induced elevation of plasma corticosterone levels in rats by a specific inhibitor of serotonin uptake. The ability of L-5-hydroxytryptophan (L-5HTP), a serotonin precursor, to elevate plasma levels of corticosterone in rats was confirmed. Pretreatment of the rats with 3-(p-trifluoromethylphenoxy)-N-methyl-3-phenyl-propylamine hydrochloride (Lilly 110140) markedly enhanced the elevation of corticosterone levels  by L-5HTP. Since Lilly 110140 is a specific inhibitor of serotonin uptake, these results support the hypothesis that L-5HTP elevates corticosterone by enhancing neurotransmission through a serotoninergic pathway influencing ACTH release.


Liver volume estimated by ultrasonic scanning before and after portal decompression surgery. In 12 patients with cirrhosis of the liver, determination of the liver volume by ultrasonic scanning and of the galactose elimination capacity (GE) were made before and after portal decompression surgery. The liver volume decreased significantly, with a median decrease of 402 ml (psmaller than 0.01). Also the GE decreased, but relatively less than the liver volume, so that the calculated GE per unit liver volume increased, with a median increase of 5 mg per minute times 100 ml liver volume (psmaller than 0.005). The decrease in liver volume following portal decompression is assumed to be due in part to reduction of liver blood volume, in part to loss of tissue water and fat, and probably to some loss of parenchyma, accounting for a reduction of the GE.


Preoperative liver function tests correlated with encephalopathy after porta-caval anastomosis. In 31 patients with cirrhosis of the liver undergoing porta-caval shunt surgery, the prognostic value of some liver function tests was studied. The surgical mortality was not correlated with the test results. Serum concentrations of bilirubin, albumin, and prothrombin were not correlated with postoperative encephalopathy, but the mutually correlated preoperative galactose elimination capacity and age of patients were correlated with encephalopathy development. Incapacitating encephalopathy mainly occurred in patients above 60 years of age, and when the galactose elimination capacity was at or less  than an arbitrary limit of 225 mg/min. The liver function decreased significantly following operation.


The use of a short-lived radionuclide in the investigation of acute bleeding in the upper gastrointestinal tract. A method is described for the detection and monitoring of bleeding in the upper gastrointestinal tract. A short-lived radionuclide (113In-m) is used. Acute bleeding in the upper gastrointestinal tract in patients without signs of shock and preshock usually stopped within a short time after onset.


[Problems of aortocoronary bypass. Indications for coronary angiography and ventriculography; results of direct bypassing coronary surgery]. The introduction of selective coronary arteriography and aorto-to-coronary saphenous vein bypass surgery (a.-c bypass) has fundamentally altered our understanding of ischemic heart disease (IHD). The indications for the effective diagnostic procedure and the results of the new and increasingly important surgical technique are summarized. Selective coronary arteriography should be performed (a) in patients with known IHD in order to furnish the anatomical and functional information necessary to assess the indication for surgery, i.e. in patients below 60 years with intractable stable or unstable (impending infarction) angina. It is rarely indicated in patients with an old myocardial infarction who are free from symptoms. It is debatable in patients during the acute stage of infarction; (b) in patients with questionable IHD, with the aim of ruling out or confirming the condition, i.e. mainly in patients with atypical chest pain or with equivocal ecg findings. The risks of the procedure, if carried out by experienced personnel, are small. Selective arteriography will always be supplemented by a selective left ventricular angiography yielding important information concerning the functional behaviour of the myocardium. In judging the therapeutic value of a.-c. bypass surgery it should be noted that postoperatively 60 to 70 percent of the patients present without symptoms and 80 to 95 percent feel markedly better, and that physical performance is enhanced in about the same proportions. An improvement in left ventricular function under exercise conditions seems to be rare. Hospital mortality of a.-c. bypass operation is small and below 5 percent if patients with stable angina and without myocardial failure, previous infarctions or mitral regurgitation are considered. In the presence of an ischemic cardiomyopathy, on the other hand, the mere surgical risk soon reaches prohibitive limits. The incidence of early complicating myocardial infarctions ranges around 10 percent. Bypass occlusion occurs in some 5 to 15 percent during the early postoperative phase, while in the following months and years the patency rate diminishes but little. If the survival rates of operated and non-operated patients with IHD are compared it becomes evident that a prolongation of life is possible whenever surgery aims at a correction of two- and three-vessel disease (including the prognostically unfavourable isolated stenosis of the left anterior descending branch and stenosis of left main artery) whereas the natural course of isolated lesions of the right coronary artery and the left circumflex branch seems to balance the effect of corresponding surgical interventions. It should be borne in mind, however, that the follow-up periods on which these statements are based do not exceed 3-4 years.


[Dyserythropoietic anemai].

[Dyserythropoietic anemai]. A systematic study of dyserythropoietic conditions has been conducted in the light of present knowledge and the author's experience. Cytomorphologic and cytochemical investigations have been made of the following hemopathies: 1. primary idiopathic dyserythropoietic anemia morphologically similar to types I, II and III but noncongenital and without a positive acidified-serum test; 2. a special form of dyserythropoietic anemia associated with dyshemopoietic genotypical mucopolysaccharidosis, a new ly recognized from of inherited mucopolysaccharide storage; 3. dyserythropoietic anemia in a patient with homozygosity due to increased isolated HbA2, a Cooleg-like anemia characterized by very long survival without transfusion treatment; 4. dyserythropoietic changes prior to any treatment in the bone marrow of cases of promyelocytic, myelomonocytoid and basophilic leukemia. The cytomorphologic and serologic features of this clinical material are discussed. Particular reference is made to a new finding, i.e. phagocytosis of degenerated erythroblasts by Alder's granuloblasts, as a new form of congenital dyserythropoietic anemia. Finally, a further dyserythropoietic condition is pointed out which is related to human fetal erythropoiesis and characterized by a large number of reticuloerythroblast islets and a dyserythropoietic pattern. However, although it appears to point to ineffective erythropoiesis this last condition cannot be considered as pathologic but as a teleologic hemopoietic phenomenon.


[Vestibular dizziness. Differential diagnosis and therapy]. Dizziness includes a wide variety of subjective sensations which are not conclusive as to their localization or pathogenesis. Even in the absence of other symptoms an analysis of dizziness, including consideration not only of its occurrence but also of its quality and course, can suggest several possibilities for differential diagnosis. We differentiate between positional vertigo, permanent vertigo and attacks of dizziness, which may be of long or only short (seconds to few minutes) duration. Based on this classification the differential diagnosis of vestibularly-induced dizziness, which ranges from distinct entities of peripheral disease (acute vestibulopathy, Ménière's disease) to symptomatic forms of peripheral or central pathogenesis, is discussed. The symptomatic medical treatment of vestibular dizziness is based on sedation of the central vestibular system. Translabyrinthine vestibular neurectomy is the treatment of choice for drug resistant Ménière's disease with a high frequency of attacks.


Human lymphocytes:  similarity of B and T cell surface morphology. When viewed by scanning electron microscopy human lymphocytes fixed in suspension and processed with minimal cell loss appear uniformly covered with short microvilli. Contrary to previous reports, lymphocytes from subpopulations selectively enriched for T cells are villous and indistinguishable from B lymphocytes. Whereas lymphocyte surface architecture can change rapidly and substantially in response to environmental modifications, such as contact with an underlying surface, these alterations are similar for both B and T cells and do not serve to distinguish these subpopulations.


Intrahepatic cholangioenteric anastomosis in carcinoma of the hilus of the liver. It is important to expand the indications for resection of tumors of the hilas, generally requiring associated hepatectomy, after careful search for metastases and biopsy of any suspicious areas makes this reasonable. One can justify such a procedure, representing a major stress and a considerable mortality rate, only if one is sure that all the tumor will be removed. If resection cannot be carried out, a unilateral intrahepatic cholangioenteric anastomosis with preference for the round ligament technique is an excellent procedure when properly applied. If a contraindication to a left sided anastomosis exists, particularly invasion of the left sided confluences, the anastomosis is made on the right to the duct of segment V. Study of the cholangiogram with attenion to the primary and secondary confluences directs a decision to perform a double anastomosis the ducts are not dilated or a poor quality anastomosis is all that can be achieved on one side and when secondary confluents are involved on both sides. The results of a variety of techniques emphasize the importance of the cholangiogram in choosing the location of an anastomosis and the role of invasion of primary and secondary conversions in choosing the technique. Many of thse patients are young and, even if no resection is possible, amy survive several years. A renewed sense of well being and prolongation of life are achievable goals even if the tumor cannot be removed. There is every reason to offer the maximum to these patients so that, if they muse eventually die, it will be from the tumor itself and not from its biliary complications.


Incidence and prevention of pulmonary embolism after coronary artery surgery. Pulmonary embolism is one of the common complications of aortocoronary artery graft surgery. During one year period, 22 patients had documented evidence of pulmonary embolism out of 231 patients who were operated. There were four deaths and all confirmed by autopsy. Clinical signs of phlebitis were absent in many cases of pulmonary embolism. Elastic stockings were not effective to prevent phlebitis. Heparin did not prevent deaths in all four patients. Heparin therapy and aggressive caval interruption by Modin-Uddin umbrella has eliminated deaths in the last 450 cases.


[Obtaining specific non-adsorbed sera to Haemophilus influenza for the agglutination test on glass]. Type-specific agglutinating sera to capsular antigenas of H. influenzae were recovered (from 1:3200 to 1:25600). With the given immunization scheme there formed mostly IgG immunoglobulins, and only insignificant amount of IgM (separation of G-200 Sephadex gel). IgG were found to be responsible for the type-specificity of the sera to bacteria, whereas the cross reactions within the H. influenzae genus were connected connected with the IgM. Use of the sera heated at various temperature regimens offered a possibility of obtaining highly specific agglutinating sera with the aid of which express serodiagnosis of the isolated H. influenzae strains was possible.


Lupus-like syndrome associated with pulmonary reaction to nitrofurantoin. Report of three cases. A systemic lupus erythematosus-like syndrome developed simultaneously with pulmonary reactions of the chronic type in three female patients after treatment with nitrofurantoin for 12, 27 and 38 months, respectively. The syndrome was characterized by elevated ESR, polyclonal hypergammaglobulinaemia, the presence of IgG antinuclear antibodies and a positive latex-fixation test. Two patients had severe arthralgia and one of them peripheral lymphadenopathy. Pleural effusion and a chronic active hepatitis were present in the third patient, in whom interstitial cystitis also developed. All signs and symptoms of the lupus-like syndrome disappeared, without corticosteroid or other medication, when nitrofurantoin was omitted. The diminution of pulmonary infiltrates and the reversal of interstitial cystitis also appeared to be directly related to cessation of nitrofurantoin therapy. Our findings indicate that long-term medication with nitrofurantoin may cause, in addition to pulmonary changes, a simultaneous lupus-like syndrome our data also raise the possibility that interstitial cystitis may occur as an adverse reaction to nitrofurantoin therapy.


Hypernatremia following gastrointestinal bleeding in cirrhosis with ascites. 3 patients with hepatic cirrhosis and ascites underwent increased diuresis on six occasions, closely related to episodes of gastrointestinal bleeding. In each instance the increased urine volume was preceded by a sharp increase in blood urea nitrogen, presumably due to absorption of nitrogenous compounds from the gastrointestinal tract, suggesting a mechanism of osmotic diuresis. In each case there was a signigicant increase in serum sodium and osmolality, related to the greater-water-than-sodium diuresis induced by urea, which was promptly reversed by the administration of water or isotonic solution. Clinically this syndrome may be defined as the association of hypernatremia and hyperosmolality due to osmotic diuresis from urea appearing in a cirrhotic patient with ascites and gastrointestinal bleeding.


Alcohol injury to gastric mucosa in mice and its potentiation by stress. This investigation was initiated to separately evaluate the roles of dose and concentration of ethanol ingestion in the development of acute gastric mucosal injury and to determine the significance of stress as a potentiating factor in ethanol damage. A total of 423 mice were used in this study. Alcohol at the low concentration of 10% and at any of the doses used (1-5 g/kh wt) did not cause gastric mucosal lesions. Similarly, alcohol at the low dose of 1 g/kg wt at any of the concentrations used (10-50%) did not produce any gross injury to the stomach. A single oral administration of ethanol, given at doses of 2-5 g/kg wt and at concentrations of 25-50%, resulted in hyperemia and multiple fundic erosions and, less frequently, antral erosion. The incidence, number, and severity of these lesions rapidly increased with increase in ethanol concentration, ethanol dose, or both. Healing was rapid; at best, lesions were only barely visible 72 hours after alcohol ingestion. Repeated daily doses of ethanol given for 3-5 days did not increase the incidence and number of lesions, probably due to their capacity for rapid healing. Mild stress, in the form of 1-hour restraint in the cold room at 8 degrees C, by itself caused very little mucosal injury in mice, but significantly potentiated the injurious effect of 35% ethanol administered in a 3 g/kh dose. Stress following alcohol intake potentiated gastric mucosal injury much more than if the stress preceded the alcohol ingestion. The incidence, number, and severity of erosions was here 3,4 and 11 times, respectively, greater than the additive effect of alcohol and stress together (P smaller than 0.001). Thus, the extent of ethanol damage to the stomach related both to the concentration and dose of ethanol infested. Stress, especially when following excessive ethanol intake, was a highly significant factor in the potentiation of acute alcoholic gastric mucosal injury.


The effect of neuraminidase on genetic variants of alpha anitrypsin. Sera of Pi types M, F, S, Z, IM, FM, MS, and MZ were incubated with neuraminidase and the reaction products followed by electrophoresis. The alpha1 antitrypsin components showed a series of changes in mobility as sialic residues were removed. Removal of sialic acid was confirmed by chemical assay. Results of studies with two different electrophoretic systems suggested that the Z type alpha1 antitrypsin has less sialic acid than the M, F, and S types. There was no evidence that other genetic variants have a reduced sialic acid content. The two major bands of alpha1 antitrypsin seen in certain electrophoretic systems may reflect a difference of one sialic acid residue. It is proposed that the Z protein lacks a carbohydrate chain with two terminal sialic acid residues. This carbohydrate deficiency results in lack of secretion of type Z alpha1 antitrypsin from the endoplasmic reticulum, perhaps because of binding to sites specific for the incomplete glycoprotein or because of aggregation of the Z asialo protein. A carbohydrate chain could be prevented from attaching to the Z type either because of a conformational change or because of the replacement of a carbohydrate-binding asparagine residue in the Z protein.


Mass screening of newborn Swedish infants for alpha antitrypsin deficiency. During the first year of mass screening for alpha1 antitrypsin deficiency, 108,000 newborn Swedish infants were examined. The screening method and criteria used for selecting infants with alpha1 antitrypsin deficiency were reliable. The Pi Z phenotype occurred at a rate of one per 1,433 infants, and the PiZ allele frequency was .026. The Pi- allele was found in one Pi Z and one Pi S infant. The Pi- allele frequency probably was below .001.


Improved long-term survival after aortocoronary bypass for advanced coronary artery disease. Three hundred thirty patients undergoing coronary bypass grafts for disabling angina, "preinfarction" angina, or coronary occlusion without cardiogenic shock have undergone coronary revascularization from July 1970 to March 1974. The operative mortality was 1.2 per cent and the long-term mortality, 4 per cent. Patients were subjected to life table analysis, and the figures suggest that in patients with two- and three-vessel coronary artery disease who received complete revascularization, there was a significant prolongation of life when compared with data from a large series of medically treated patients with angiographically documented coronary artery disease. Longer follow-up data will be important in definitively ascertaining the favorable effect of coronary revascularization on longevity.


Ultrastructural variation in granular dystrophy of the cornea. Corneal deposits of granular dystrophy were studies in six corneas from five patients. Two additional corneas from two patients with lattice dystrophy were used for comparison. The diagnoses were confirmed by light and electron microscopy. Three types of ultrastructural features were distinguished in the electron-dense rod-shaped deposits of granular dystrophy, i.e., Type 1 with homogenous structure, Type 2 with fibrillar constituents, and Type 3 with a moth-eaten or sponge-like appearance. In polarization microscopy of Congo-red stained sections, the Type 2 tended to show an increased birefringence without green dichroism, while the other types were less birefringent than the stroma. Three different components were found immediately around the deposits, i.e., 1. normal collagen fibrils, 2. finely filamentous substance, and 3. areas of thin fibrils (70-100 A in diameter). While the second component appeared non-specific, the third component was found only in two corneas, superimposed on the lesions of granular dystrophy, and showed light and electron microscopic characteristics of the lesions of amyloid as well as of lattice dystrophy.


Goldmann applanation versus hand-applanation and .schiötz indentation tonometry. For evaluation of hand-applanation tonometry comparative measurements of intraocular pressure have been carried out using the Goldmann applanation tonometer, the Draeger and Perkins hand-applanation tonometers and the Schiötz indentation tonometer. A series of 52 eyes has been tested. The statistical analysis was based on the Goldmann tonometry as a reference system. The hand-applanation tonometers were found to be in satisfactory agreement with the Goldmann tonometer, whereas the Schiötz tonometer gave significantly low values in the pressure range considered.


[Intraocular pressure after changing the patient's position (author's transl)]. The influence of the patient's position (sitting or supine) on the intraocular pressure has been examined by means of Goldmann applanation-tonometry. The statistical analysis shows that the intraocular pressure decreases after the first measurement. This is the reason for measuring higher values in the first position, irrespective wether the first measurement is done in sitting or supine position. Analysing the values of steady state pressure i.e. 12 min after taking or changing position indicates a little higher mean value of intraocular pressure in the sitting position of the patient. The difference of mean valuse of sitting ans supine position of the patient is not significant. There are patients who have always higher others have always lower values of intraocular pressure in the supine position. These observations described earlier by Strobl and Follmann, have been confirmed by repeated measurements on 19 patients with differences in both directions of 2 to 4 mm Hg. For this reason it seems not feasible to use a statistical mean value of a population to correct the intraocular pressure of a particular case after changing position.


[Identification of zonula fiber protein by disc-electrophoresis (author's transl)]. By our investigations we found identity of collagen and zonula fibers protein. In Disk-electrophoresis both the zonula fibers ans the fibers of the vitreous show the alpha-component only. Therefore it is likely that these proteins are closely related.


[Determination of bovine aqueous humor proteins (author's transl)]. By turbidimetry, Disk-electrophoresis, combined Disk-immunomethod, and single radial immunodiffusion it was possible both to identify some proteins and to determine the protein content and the albumine concentration of bovine aqueous humor.


Alkali and acid burns of the rabbit eye: uptake of intravenously injected Na125I and Na131I into the cornea and iris. Rabbit eyes were burned either with 1 N sodium hydroxide or 1 N hydrochloric acid. In a previous part of the study (Obenberger and Babický, 1974) authors measured the aqueous flow using intravenous injections of Na125I and Na 131I. In the present study the uptake of iodine into the cornea and iris is investigated in the same eyes. Caustic injuries of both types initially cause changes in the specific activity of the aqueous affecting the uptake of iodine into the examined tissues.


Immunologic studies in patients with recurrent bronchopulmonary infections. In view of the known association of several different immune deficiency disorders with infections of the respiratory tract, a number of immunologic parameters were investigated in 15 patients with recurrent brochopulmonary infections. The patients' neutrophils all demonstrated normal intracellular killing of Staphylococcus aureus, and responded normally to chemotactic stimuli. Although assays of complement 3c were normal in all patients' sera, defective total hemolytic complement activity was consistently shown in 1 patinets manifested elevated serum immunoglobulin concentrations. Severe alpha1 -antitrypsin deficiency (Pi ZZ phenotype) was discovered in 1 patient. Three patients displayed cutaneous anergy to a battery of skin-test antigens, but lymphocytes from all patients studied responded normally to in vitro phytohemagglutinin stimulation. A "blocking" factor found in the serum of 3 patients suppressed the in bitro transformation of normal Candida-responsive lymphocytes by Candida albicans antigen. "Cold" lymphocytotoxins were detected in the sera of 10 patients, but in only 3 of 19 control sera. Although the significance of these findings is unknown, they may possibly have pathogenetic relevance in a small number of the patients studied.


Transvestibular approach to the internal auditory canal. Summary--A surgical approach to the internal auditory canal is presented which as proved useful in the following circumstances: 1) as a destructive procedure in Ménière's disease, 2) as a diagnostic procedure in patients in whom an acoustic neurinoma is suspected and a labrinthectomy is indicated. In this situation the tumor may be removed during the same operative procedure, 3) for the removal of small, mobile, intracanalicular neurionomas, and 4) for complete facial nerve decompression in patients with no vestibular response and no serviceable hearing.


Studies with Brugia pahangi. III: Histological changes in the affected lymph nodes of infected cats. Cats infected with Brugia pahangi by single or repeated inoculation of infective larvae for different periods of time, were autopsied and the affected lymph nodes examined histologically, stained with methyl green and pyronin Y, haematoxylin and eosin, Lendrum's eosinophil stain, Mallory's trichrome stain or the May-Grunwald Giemsa technique. In single infections, there was initially a cell-mediated type immunological response which was characterized by proliferation of mononuclear thymus-dependent cells in the paracortical region of the lymph node. The antibody-type response became more evident as the infections progressed. This response was characterized by proliferation of lymphocytes in rapidly enlarging germinal centres and the production of large numbers of plasma cells in the cortico-medullary junction and medullary cords of the nodes. In long term infections, the affected afferent lymphatic vessel and popliteal node were almost obliterated by fibrous tissue, but an inguinal lymph node complex usually developed to replace lymphatic filtration in the limb. Repeated infections produced more complicated changes. Both types of response occurred to varying degrees throughout the infection. No significant increase in mast cells or eosinophil cells was seen. Fibrous tissue increased in the lymph nodes only after long periods of infection; such nodes often became non-functional, and by-passed by new lymphatic vessels.


Simplified circular aortotomy in aortocoronary bypass operations. Adaptation of a rongeur technique facilitates aortotomy in aortocoronary bypass operations. A single motion with a double-action duckbilled rongeur produces a smooth-walled, symmetrical aortotomy which varies in shape predictably according to the angle at which the rongeur is held relative to the axis of the aorta.


Sarcoplasmic masses. Enzyme histochemistry and autoradiography. A comparative enzyme-histochemical study was made of the sarcoplasmic masses in a muscle biopsy specimen from a patient with myotonic dystrophy and those in the jaw-muscle of the Rana temporaria tadpole. The enzyme-histochemical patterns of the two methods proved to be identical. An autoradiographic study was made of the sarcoplasmic masses in the R temporaria tadpole with DL-thyroxine-2-14C and levomethionine 35S. The radioactivity labeled compounds were found to be stored or incorporated mainly in the myofibrillae, and virtually not at all in the sarcoplasmic masses.


[Histogenesis of the immune system of the "nude" mouse. Postnatal development of the thymus: a light microscopical study (author's transl)]. Mice homozygous for the mutation "nude" display a dysgenetic thymus (Pantelouris, 1968). The anterior mediastinum of these animals contains a rudimentary epithelial organ (pantelouris and Hair, 1970), which has been assumed to represent not a maldeveloped thymus, but rather a remnant of the parathyroid gland or of the ultimobranchial body (Wortis et al., 1971). We have investigated the development of the thymus in homo- and heterozygous nude by both light and electron microscopy. This paper describes the light microscopical findings in embryos and fetuses from the 11th up to the 18th day post conceptionem (pc). Homo- and heterozygous nude (nu/nu + nu/+) mice with the genetic background BALB/c were kept under specific pathogen-free (spf) conditions. Virgin nu/+ females were mated with nu/nu males. In addition, homozygous females were mated with homozygous males in order to investigate 11-day-old homozygous embryos. The embryos and fetuses were fixed in Bouin's solution and embedded in paraffin wax. Serial frontal sections (5mu) were stained with hematoxylin and eosin. Up to the 12th day pc, the thymus anlage of the n/nu embryo is indistinguishable from that of the nu/+ animal. The paired anlage develops from the epithelium of the ventral and dorsal diverticles of the 3rd pharyngeal pouch, and from the ectodermal vesicula cervicalis. In the nu/+ embryo, the thymic epithelium begins to proliferate between the 12th day and 13th day pc. In the central part of the anlage, the epithelial cells dissociate and begin to form a reticulum. At the same time, blood vessels from the surrounding mesenchyme invade the anlage. From the 14th day onwards, lymphoblasts are recognizable..


Fate of coronary collateral circulation after aorto-coronary saphenous vein bypass grafts. The pre- and postoperative patterns of coronary artery collateral circulation have been studied in 34 patients who had saphenous vein bypass grafting. When the graft remained patent homocoronary collaterals could not be visualized after operation, but new intercoronary anastomoses frequently developed to other diseased arteries. When the graft and the bypassed artery were both obstructed there was a high incidence (5 out of 11) of myocardial infarction despite good preoperative collaterals.


Effect of aorto-coronary grafts and native vessel patency on the occurrence of angina pectoris after coronary bypass surgery. Exercise testing of 52 patients on average 11 months after coronary bypass surgery for the relief of angina pectoris disclosed improvement in total work (P is less than 0.001), maximal tolerated load (P is smaller than 0.001), maximal heart rate (P is smaller than 0.01), and reduction of maximal ST segment depression (P is smaller than 0.001) in a group of 36 patients with all grafts patent. In another group of 16 patients with one or more grafts occluded the only significant change was a reduction in the maximal ST segment depression (P is smaller than 0.01). Early and late postoperative angiograms showed that 75 per cent of the grafts that became occluded were already closed a few weeks after operation. Occluded grafts were accompanied by persistence of collaterals, which disappeared or dimished in the majority of patients with patent grafts. Progression in native vessel lesions occurred in 40 per cent of patients.  It was related to the grafting procedure (P is smaller than 0.01) but not to the state of grafts. The change in native vessels and other variables studied was equal in the patent and occluded graft groups, justifying the conclusion that graft patency was the major factor alleviating angina after operation.


Secondary postpartum haemorrhage.

Secondary postpartum haemorrhage. The clinical features of 106 women who had a secondary postpartum haemorrhage were examined in detail; 39 were managed conservatively, 3 had a vaginal laceration resutured and 64 had a curettage. In 46 patients, material obtained by curettage was examined histologically. The clinical features associated with retained products of conception are defined and comparisons are made between conservative and surgical management of secondary postpartum haemorrhage.


Secondary anterior crocodile shagreen of Vogt. The clincopathological features and pathogenesis of secondary mosaic degeneration of the cornea (anterior crocodile shagreen of Vogt) are described. The structural basis for the normal anterior corneal mosaic pattern seems to lie in the particular arrangement of many prominent collagen lamellae of the anterior stroma that thake an oblique course to gain insertion into Bowman's layer. Since, at normal intraocular pressure, Bowman's layer is under tension, when viewed from the anterior surface the cornea appears smooth. By releasing the tension, however, a reproducible polygonal ridge pattern becomes manifest. It is suggested that a prolonged phthisical state of the eye is one condition wherein the mosaic pattern may become permanent and that, as a secondary event, this is followed by irregular calcification of Bowman's layer which particularly involves the ridges projecting into the epithelium. Biomicroscopically these ridges corresponded to the branching reticular arrangement of the mosaic opacities.


The metabolism of some folates in the rat. 1. A number of folates labelles with 14-C were administered orally to rats, at various doses, and urinary, faecal and hepatic folates examined. 2. 10-Formylpteroylmonoglutamic acid ( 10CHO--PGA) entered the folate pool very slowly, and is thought to be relatively ineffective in nutrition. 3. 10-Formyl[2-14-C]tetrahydrofolic acid (10CHO--[2-14-C]THF) entered the folate pool very rapidly. 5-Methyl[2-14-C]tetrahydrofolate (5CH3--[2-14-C]THF) was the major urinary folate. 4. 5-Formyl[2-14-C]tetrahydrofolic acid (5CHO--[2-14-C]THF) entered the folate pool only to a small extent. 5CHO--[2-14-C]THF, given intravenously, produced no urinary 5CH3--[2-14-C]THF in the first 6 h. 5. 5,10-Methylidyne[2-14-C]tetrahydrofolic acid was metabolized to an extent which was dependant on the dose. At doses of 3 and 30 mug/kg body-weight, 5CH3--[2-14-C]THF represented 5-4 and 20% respectively of urinary folates anf for 10CHO--[2-14]PGA, the values were 16% of total urinary folates after the higher dose, and 78-5% after the lower dose. 6. Results obtained for the metabolism of 5CH3--THF varied depending on the position of the labelling: 5-14-CH3-THF gave no labelled urinary folate, the methyl group being lost rapidly. When 5CH3--[2-14-C]THF was given, it appeared as the major urinary folate. 7. Folates found in the liver after oral administration of labelled folates were identified by thin-layer chromatography; only folate monoglutamates were identified.


Membrane biosynthesis in the frog retina: opsin transport in the photoreceptor cell. Rhodopsin biosynthesis and transport in the photoreceptor cell have been analyzed by subcellular fractionation of frog retinas after short periods of radioactive amino acid incorporation in vivo. Labelled membrane proteins were identified by autoradiography or sodium dodecyl sulfate-polyacrylamide gels. One of the most intensly labeled proteins in retina had a molecular weight comparable to opsin isolated from purified rod outer segments (ROS). Incorporation of label into this protein was rapid; the relative specific activity then diminished after the first 2 hr as radioactivity was transferred from retinal subcellular fractions to ROS. The kinetics of this transfer resembled rates previously observed by Hall et al. (Hall, M. O., Bok, D., and Bacharach, A.C.E. (1969), J. Mol. Biol. 45, 397). To identify the rapidly labeled protein as opsin we devised a new technique of two-dimensional immunoelectrophoresis of detergent solubilized membrane proteins. Antibodies were prepared against both whole ROS and opsin. After initial separation of retinal proteins on sodium dodecyl sulfate-polyacrylamide gels, a second dimension of electrophoresis in agarose, containing antisera, resulted in the formation of specific immunoprecipitates. Immunochemical analysis of all membranous and soluble retinal subcellular fractions indicated that newly synthesized opsin was membrane bound upon completion of synthesis. At no period of incorporation was a soluble form of newly synthesized opsin detectable. On this basis, we suggest that this protein is apparently transported as a water-insoluble membrane-bound molecule through the cytoplasm or along membranes of the inner segment to its assembly site near the base of the outer segment.


Optical diffraction study of muscle fibers. Skeletal muscle fibers act as a one-dimensional grating to electromagnetic waves in the optical frequency range. Results are presented of the optical diffraction study of frog sartorius muscle fibers. 1. A simple theoretical consideration predicts that, at a sarcomere length near 3 mum, the second-order reflection is contributed only by the thin filaments due to the destructive interference between scattered rays from thick filaments. At that sarcomere length, both the first-order and the third-order reflections are contributed by both kinds of filaments. 2. Intensity measurements of diffraction lines of muscle fibers at rest at various sarcomere lengths confirmed the validity of our theoretical prediction.3. The isometric contraction of skinned fibers was realized by the phoretic injection of Ca2+ from a micropipette. During the Ca2+ injection intensity drops of the diffraction lines were observed. At a very narrow range of sarcomere lengths near 3 mum, the intensity drop of the second-order diffraction line became very small on Ca2+ injection, whereas the intensity drops of both the first-order and the third-order diffraction lines were very large. 4. A theoretical analysis concludes that the intensity drops on Ca2'njection are solely due to small random fluctuations of the position of thick filaments in the sarcomeres.


X-ray diffraction studies of retinal rods. I. Structure of the disc membrane, effect of illumination. The structure of the retinal rod disc membrane and its modifications upon bleaching have been studied by X-ray diffraction. Three types of preparations are used: functioning isolated from retina, isolated rods from frog retina, oriented by a magnetic field, and stacked discs from cattle retina. X-rays are detected by a position-sensitive linear counter. Diffraction spectra are obtained in 10-100 s. The electron density profile favors models where the rhodopsin molecule spans the whole thickness of the membrane. Upon bleaching, a small increase of electron density appears instantly at the cytoplasmic edge of the membrane. In the intact retina this structural change is accompanied by disorder and slow swelling reactions which are not observed in the isolated rod outer segment. The diffraction signal arising from the protein distribution in the plane of the membrane has been reinvestigated carefully. Patterns identical to those of Blasie (Blaise (1969) J. Mol. Biol. 39, 407 and Blaise (1972) Biophys. J. 12, 191) can be obtained but these are shown to be dominated by artefacts. The actual signal is a single broad band around (55 A)-1, upon which bleaching has a negligible effect. No measurable displacement of rhodopsin in the thickness of the membrane occurs upon bleaching. Temperature effects on the protein distribution are found to be large only for disc membranes from cattle retina. In this material from a warm-blooded animal those effects are correlated with the occurrence, upon lowering the temperature, of a partial phase transition of the paraffin chains of the lipids. The position and the slope of the transition are not sensitive to bleaching.


X-ray diffraction studies of retinal rods. II. Light effect on the osmotic properties. A fast X-ray diffraction technique has been used to study the osmotic reaction of frog rod outer segments to bleaching and to changes in the osmolarity and composition of the outer medium. Dissected excitable retina and isolated outer segments have been used. Upon bleaching in isotonic Ringer only a small transient diminution of the disc repeat distance is observed in isolated rods. Disorder and slow swelling reactions are also observed in the intact cells. In calcium-free Ringer the light-induced shrinkage is considerably enhanced. In the intact cell this is interpretable as due to the switching off of a large sodium dark current. The persistence of the effect in isolated outer segment suggests the existence of an active ionic efflux from this part of the cell. Upon hypotonic shock, bleached rods swell more than dark-adapted ones. The difference, however, appears only in a slow component of the osmotic kinetics, a few minutes after the shock. Upon hyertonic shock, part of the rods, even in the "intact" excitable retina, appear to be leaking. Those cells which are intact are impermeable to all the solutes added to increase the osmolarity: NaC1, KC1, Sucrose, Melezitose. No light dependence of the response to a hyperosmotic NaC1 shock is detectable. The discs are osmotically reactive, even when the outer cell membrane of the rods is leaking. Assuming the discs to be perfect osmometers, a thickness of 20 plus or minus 5 A is estimated for the liquid layer inside the discs.


Excited states of photosynthetic reaction centers at low recox potentials. In preparations of photochemical reaction centers from Rhodopseudomonas spheroides R-26, lowering the recox potential so as to reduce the primary electron acceptor prevents the photochemical transfer of an electron from bacteriochlorophyll to the acceptor.  Measuring absorbance changes under these conditions, we found that a 20-ns actinic flash converts the reaction center to a new state,  P-F, which then decays with a half-time that is between 1 and 10 ns at 295 degrees K.  At 25 degrees K, the decay half-time is approx.  20 ns.  The quantum yield of state P-F appears to be near 1.0, both at 295 and at 15 degrees K.  State P-F could be an intermediate in the photochemical electron-transfer reaction which occurs when the acceptor is in the oxidized form.  Following the decay of state P-F, we detected another state, P-R, with a decay half-time of 6 mus at 295 degrees K and 120 mus at 15 degrees K.  The quantum yield of state P-R is approx. 0.1 at 295 degrees K, but rises to a value nearer 1.0 at 15 degrees K.  The kinetics and quantum yields are consistent with the view that state P-R forms from P-F.  State P-R seems likely to be a side-product, rather than an intermediate in the electron-transfer process.  The decay kinetics indicate that state P-F cannot be identical with the lowest excited singlet state of the reaction center.  One of the two states, P-F or P-R, probably is the lowest excited triplet state of the reaction center, but it remains unclear which one.


Diffusion resistance of endothelium and stroma of bullfrog cornea determined by potential response to K+. Corneas of bullfrog (Rana catesbeiana) were mounted between lucite chambers. A four-electrode system was used and the potential difference (PD) and the electrical resistance were measured. In intact corneas, the PD averaged 25 mV (acqueous side positive) and the electrical resistance 1.5 kQ - cm2. perfusion of the aqueous side with high K+ solutions resulted in a marked decrease in PD and a drop in the electrical resistance. Scraping the epithelium (leaving the stroma plus endothelium) resulted in a drop of the PD to about zero and a decrease in electrical resistance to about 0.1 kQ - CM2 and a very small PD response to a marked elevation of the K+ concentration on the aqueous side. On the basis of the above, it is obvious that the large delta PD in intact corneas, due to elevation of the K+ concentration, must be due to K+ diffusing from the aqueous side across the endothelium and stroma and reaching the epithelium. The duration of the PD response is therefore a measure of the resistance to diffusion of the stroma plus endothelium. A quantitiative analysis shows that under in vitro conditions the resistance of the endothelium plus stroma to the diffusion of ions is very low.


Pulsed nuclear magnetic resonance study of 17-O, 2-D, and 1-H of water in frog striated muscle. Whole gastrocnemius muscles were incubated in Ringer's solution enriched with H2-17O; the paired contralateral gastrocnemius muscles were incubated in a similar solution enriched with deuterons, as well. Subsequently, the longitudinal relaxation times (T1) were measured 17-O, 2-D, and 1-H, both at 8.1 MHz and at 4.3 MHz. The results indicate that: (a) the absolute values of T1 characterizing the three nuclides are different in muscle and pure water. (b) the longitudinal relaxation rates of all three have an identical frequency dependence over the range studied, (c) the ratio (T1)2D/(T1)17ois the same in muscle water and pure water, while the ratio (T1)1H/(T1)17o is 2.1 times greater in pure water than it is in muscle water, and (d) 30-49 percent substitution of 2-D for 1-H has very little effect on the spin-lattice relaxation of tissue water protons. These data suggest that muscle water is in rapid exchange between a small fraction of immobilized molecules and a large fraction of free water. The results render unlikely the possibility that hypothetical ordering of muscle water significantly contributes to its longitudinal relaxation.


[The effect of strychnine on the muscle receptors of cold-blooded animals]. Experiments were conducted on frogs. A study was made of the functional condition of the muscle receptors by the method of recording of spontaneous and afferent impulsation induced by the strain of the gastrocnemius in the peripheral section of the sciatic nerve or in the IX-X posterior spinal cord roots. It was revealed that strychnine administered into the general circulation and applied directly into the muscle produced a reduction and that applied to the spinal cord--on the contrary--caused an increase in the impulse generation in the muscle receptors.


Hypothesis: differentiation of the human lymphoid system based on cell surface markers. Human lymphocytes can be separated into distinct populations based upon receptors on their cell surface. Thymus-derived (T-cell) lymphocytes can be identified by their ability to form rosetts with sheep erythrocytes (SRBC); bone marrow-derived (B-cell) lymphocytes bear characteristic surface markers for immunoglobulin, complement, and the Fc portion of IgG. Recently, populations of lymphocytes having either multiple markers or no detectable markers (null cells) have been observed. Based on studies of cell surface markers, a scheme is proposed that expands the known differentiation of the lymphod cell to include subpopulations which represent developmental stages. It is suggested that lymphocyte maturation involves alloantigenic changes in a circulating stem cell-drived nill cell, leading to a cell bearing markers for both T- and B-cells. It is from this latter cell that the classic T- and B-cells ultimately arise. Maturational defects which may explain the origin of primary lymphoproliferative diseases are discussed.


A genetic study of bipolar affective disorder. A group of 46 bipolar probands and their first degree relatives were studied. A high rate of affective disorder (19.6 per cent) was found, including both unipolar (13.2 percent) and bipolar (6.4 per cent) types, with females predominating (3 : 1). The presence of four fatherson pairs suffering from affective disorder made the hypothesis of X-linked dominance untenable. Results compatible with polygenic inheritance were found, using both Slater's and Falconer's methods. There was no evidence for assortative mating or for increased total number of females (both well and ill) among first degree relatives. The probands and affectively ill first degree relatives who have died show an alarmingly high rate of suicide (46 per cent). Other forms of mental disorder, including alcoholism, were no more common than in the rest of the community.


Haematemesis: a new syndrome?

Haematemesis: a new syndrome? Three patients presented with symptoms suggesting a Mallory-Weiss tear. Endoscopy showed a localized, clearly demarcated area of bright red mucosa near the gastro-oesophageal junction; this was thought to have arisen by retrograde intussusception of the stomach during vomiting or retching and may have caused the haemorrhage.


Uptake of local anaesthetics: movement of ethanol into frog sciatic nerve. The changes of nerve action potential with time of the excised bullfrog sciaticperoneal nerve were measured at 24 degrees C with the nerve immersed in oxygenated mineral oil containing various concentrations of ethanol. One series of measurements was made with intact nerve and a range of about 20 to 110 millimolar ethanol. Another series was made with nerves in which the epineural sheath was cut open longitudinally and using a range of about 15 to 51 millimolar ethanol. The results were analysed by means of simple diffusion theory, and below applied ethanol concentrations of about 70 millimolar the latent periods and times to total block fitted the theoretical pattern well. Disagreements between theory and measurement of previous workers is explainable by their neglecting to recognize that nerve bundles do not extend to the nerve periphery. It was found that the minimum oil concentration of ethanol capable of producing total block is 15 millimolar. Above 70 millimolar, behaviour was observed consistent with nerve damage. It was found possible, by measuring the ratio latent period: time to total block, to separate the relative contribution of the epineural sheath and epineurium as a diffusion barrier to ethanol from that of the perineurium and perilemma.


Bloodless open heart surgery with atraumatic extracorporeal circulation. With careful refinements in the pump oxygenator and a nonblood prime, bloodless open heart surgery may be performed almost routinely. In our series these measures reduced blood trauma, with a remarkable preservation of blood elements, especially platelets, and a corresponding elimination of postoperative bleeding. The mean hematocrit value decreased from 38 to 27% and recovered to 33% in the first 3 hours of postoperative diuresis. Mannitol and furosemide were rarely needed. Of 61 adult patients whp underwent open heart surgery for aortocoronary bypass or valve replacement, the last 43 had a bloodless procedure. Of the 43, 26 (60%) required no bank blood postoperatively (in the operating room or the intensive care unit). In these 26 the operative mortality was 4% (1 patient). Bloodless techniques are invaluable during periods of bank blood shortage. They avoid the dangers of hepatitis and transfusion reaction, and they may minimize the incidence of postperfusion lung syndrome as well as renal complications.


Quantitation of cell-mediated immunity: responses to dinitrochlorobenzene and ubiquitous antigens. T-lymphocyte immune capacity in man was assessed semiquantitatively by two in vivo procedures: the primary type of response to dinitrochlorobenzene and the secondary type of response, representing memory, to a group of five uniquitous antigens. Controlling for degree of illness proved important in assessing immune capacity in specific diseases; thus, the number of responders and mean score of semiquantitated responses was significantly lower in groups of patients with cancer and multisystem autoimmune disease when comparisons were made with healthy persons, but less so when comparisons were made with a group of subjects with other incapacitating diseases. A notable finding was the lack of correlation in the results of tests of cell-mediated immunity between the two procedures described. Depressed cell-mediated immunity shown in multisystem autoimmune disease is relevant to both predisposition to infection and the postulated role of thymic dysfunction in the pathogenesis of autoimmunity.


On electrical condution in living bone.

On electrical condution in living bone. Despite the effectiveness of electrical currents in enhancing bone repair, there is little information in the literature on electrical parameters per se. Very little is known about the nature of the conduction mechanism or the current path between the electrodes. Without a better understanding it is difficult to establish meaningful hypotheses at the cellular level and to design relevant experimental protocols. In the present work, a first attempt is made at an in vivo delineation of the current-voltage relationship in the medullary area between two platinum electrodes embedded in the femur, by one of the techniques generally known to stimulate bone growth. At potential differences of less than 1 volt, a rather good ohmic dependence is observed, with an approximate specific resistance of 2 to 5 times 10-5 ohms/cm. At potentials higher than 1 volt, electrolytic processes appear to predominate and there is increasing non-linearity. Experimental techniques involving the adjustment of current through bone tissue assuming an ohmic dependence with little or no associated polarization effects are valid and certainly warrant further investigation.


Role of 11 beta-hydroxyprogesterone in biosynthesis of corticosterone from progesterone in guinea pig adrenals. Slices of male guinea pig adrenals were incubated with trace amount of 3-H7 alpha-progesterone and the percentage of incorporation of 3-H into various steroids at various intervals was measured. It was found that 3-H accumulates predominately in 11 beta-hydroxyprogesterone as compared to DOC. This indicates that, in guinea pig adrenals, 11 beta-hydroxyprogesterone plays a dominant role in a formation of corticosterone from progesterone. The observed sequence of changes in progesterone label accumulation in 17-hydroxycompounds indicates they pathway of cortisol synthesis through the intermediate formation of 17-hydroxyprogesterone and 11-deoxycortisol.


Iodine accumulating ability as generalized porperty of cells of endodermal origin. Embryonal trachea transplanted in the spleen of adult rats accumulates iodine. The uptake of iodine does not take place in all of the cells, but iodination centers develop and the iodinated cells detach themselves to the lumen thus resembling the holocrine secreation; The results of these experiments indicate that the uptake of iodine appears to be a generalized property of the endoderm.


Effect of estradiol on the activity of serotonin N-acetyltransferase in the rat epiphysis. Administration of estradiol to ovariectomized females did not affect either the rhythm and basic levels of activity of the enzyme regulating the formation of melatonin in the rat epiphysis-serotonin N-acetyltransferase or the activation of this enzyme by isoproterenol in vivo. Daily administration of estradiol to young rats from birth did not alter the rhythm or activity of serotonin N-acetyltransferase in the epiphysis as estimated on the 8th day of age. The ability of estradiol to suppress noradrenaline activation of adenyl cyclase in epiphysial homogenates and its inability to suppress the same activation of serotonin N-acetyltransferase suggests either that the activation of the latter enzyme by catecholamines could occur by other mechanisms than the adenyl cyclase system or that activation of adenyl cyclase by noradrenaline is not suppressed by estradiol to the same degree in vivo as in vitro.


Sodium fluoride-induced changes in the hypothalamic neurosecretory system of the spotted owlet, Athene brama Temminck. Administration of 10 or 20 mg of sodium fluoride (NaF) induced depletion of neurosecretory material (NSM) from the neurons of the supraoptic (SON) and paraventricular (PVN) nuclei in spotted owlet (Athene brama Temminck). The residual NSM in the perikarya was aranged in caplike paranuclear positions. The NSM in the hypothalamo-hypophysial tract, the zona externa of the anterior median eminence (ME) and in the neural lobe (NL) showed only a partial lossmthe effects of NaF administration on the HNS of the spotted owlet are similar to those induced by such stimulators of ADH secretion as hypertonic saline, morphine and formalin. Hence the histological changes induced by NaF administration in the HNS of the spotted owlet are presumably indicative of increased neurosecretory activity resulting in the augmented secretion of ADH. It is suggested that NaF, like other stressful agents, is a stimulator of ADH secretion.


Activity of catecholamine degrading enzymes in rat adrenal medulla and cortex after acute and repeated stress. The activity of catecholamine degrading enzymes (catechol-O-methyltransferase--COMT and monoamine oxidase--MAO) in separated adrenal cortex and medulla was measured in rats stressed by a singel or repeated immobilization. In controls, the activity of both enzymes was higher in adrenal cortex than in adrenal medulla. After stress, the activity of COMT in adrenal cortex was significantly decreased, while that in adrenal medulla was significantly increased. Moreover, the animals repeatedly immobilized showed lower COMT activity in both parts of adrenals when compared to first time stressed rats. The activity of MAO was not remarkably changed, but was increased only in adrenal medulla when expressed per mg protein, the decrease of which resulted from acute stress. It was concluded that the findings of changed activity of catecholamine degrading enzymes, namely a decreased activity of COMT in both adrenal cortex and medulla in repeatedly stressed rats, might show a possible participation of these enzymes in increased catecholamine content in adrenals of repeatedly stressed animals.


Factors affecting estrogen signalization for FSH secretion in male and adrogenized or normal female rats. Factors affecting the FSH feedback mechanism in intact or androgenized females and intact males were studied by ovarian fragment implantation into the spleen. A pronounced sex difference could be observed in the ovarian hypertrophy after transplantation. Males as well as androgenized females as hosts responded more than intact females. On the other hand, ovaries originating either from normal or androgenized rats showed similar enlargement under the spleen capsule, regardless of their origin. It was concluded that the AS females have a deficit in the negative feedback signalization which seems to be due to the differences in hepatic degradation of the estrogens. Nevertheless, a change of the set-point for FSH in androgen sterile rats cannot be excluded.


Influence of left ventricular function on survival 3 to 4 years after aortocoronary bypass. Preoperative left ventricular ejection fraction (EF) was calculated using single plane cineventriculography in 93 patients in whom aortocoronary bypass surgery was performed before July 1970. Preoperative EF (mean plus or minus SEM) was 0.29 plus or minus 0.04 in 9 patients deceased between 2 and 35 mth after operation, significantly lower (p less than 0.001) than EF of 84 patients having survived 3 yr or more (0.55 plus or minus 0.02). The 3- to 4-yr mortality in these patients was 22.2% when preoperative EF was less than 0.50 and 1.75% when it was greater than or equal to 0.50 (p less than 0.01). Likewise, late mortality rose to 43.7% when EF was less than 0.40, compared to 2.6% when it was greater than or equal to 0.40 (p less than 0.005). In 21 patients in this series, left ventricular volumes and EF showed no significant difference before, approximately one year and between 3 and 4 yr after operation. This included 9 patients with normal or near normal contraction and 12 patients with impaired ventricular contraction preoperatively. Thus, in this study, preoperative EF was a major determinant of long-term prognosis after aortocoronary bypass and EF was not improved between 3 and 4 yr postoperatively. These data suggest, then, that in order to enhance survival after aortocoronary bypass, patients should be operated on before significant myocardial damage has occurred.


Acetylcholine receptors on Renshaw cells of the rat. Experiments have been performed on Renshaw cells of rats to investigate the receptors mediating both the responses to electrophoretically applied cholinergic excitants and the synaptic excitation following stimulation of the ventral roots. The effects of atropine and dihydro-beta-erythroidine, muscarinic and nicotinic antagonists respectively, have been tested on both types of excitation. Most importantly we found that in the rat the ventral root evoked response can be blocked by atropine as well as by DHbetaE. It was not possible to categorise the responses to the cholinergic agents in terms of muscarinic and nicotinic receptors. In addition we have failed the late (muscarinic) excitation seen in the cat.


The mode of action of 5-hydroxytryptophan in facilitating a stretch reflex in the spinal cat. 1. Intravenous injection of 5-hydroxytryptophan (5-HTP) excites discharges of gamma motoneurones to extensor muscles of the hind limbs of decerebrate spinal cats and this occurs with a short latency (1-2 min). 2. 5-HTP also facilitates the stretch reflex in the spinal cat but, in contrast, there is a latency of about 10 min with a maximum action after 20 min. 3. Facilitation of the stretch reflex by 5-HTP still occurs when the gamma loop has been opened by cutting all ventral roots supplying the muscle. Thus excitation of gamma motoneurones by 5-HTP is not required for facilitation of the stretch reflex. 4. A possible contribution to the stretch reflex from the increased discharge of gamma motoneurones has been assessed. Selectively removing gamma activity rarely altered the reflex response to stretch and in only 3 out of 15 spinal cats could we conclude that gamma discharges contributed towards facilitation of the stretch reflex by 5-HTP; 5; Methysergide (0.25 mg/kg) blocked completely the facilitation of the stretch reflex caused by 5-HTP in the spinal cat but only partially antagonised the reflex in the decerebrate cat, even when injected intra-arterially close to the lumbar spinal cord. 6. Lysergic acid diethylamide (LSD) was found to mimic the actions of 5-HTP. It facilitated the stretch reflex and excited extensor gamma motoneurones in the spinal animal.


Vestibular and somatosensory inflow to the vestibular projection area in the post cruciate dimple region of the cat cerebral cortex. In anesthetized cats 251 cells within the cortical vestibular projection area, adjacent to the post-cruciate dimple, were analyzed as to their input characteristics employing extracellular recording techniques. The post cruciate dimple vestibular field, which is located in area 3a, has a high degree of convergence between vestibular and peripheral somatosensory input. The latter is not restricted to muscle afferents but includes cutaneous modalities. The functional significance of this vestibular cortical projection field is discussed.


[Changes in the ultrastructure of frog spinal cord motor neurons following low frequency stimulation of afferent fibers]. Effect of 10 min stimulation on the motoneurones ultrastructure depended on the amplitude of the ventral root biopotentials.  In case of low amplitudes dilated endoplasmic spaces, Golgi complex cisterns were seen.  Mitochondria were swollen and the number of free ribosomes increased.  In the cytoplasm many "whorl--like" structures appeared.  In case of high amplitude ventral root biopotentials, alterations were particularly evident in decrease in the ribosomes number, fragmentation of the endoplasmic reticulum.  Electron density of the motoneurons was very low.  After 25 min stimulation, the number of ribosomes increased in the motoneurons, the Golgi complex proliferated, very large mitochondria appeared.  In the dendrites, swollen mitochondria often were adjacent to postsynaptic membranes.  Electron density of the motoneurons was very high.  The ultrastructural alterations of the motoneurons are supposed to be due to a change of cellular metabolism in the conditions of increased functional activity.


The part played by cell-mediated immunity in mycoplasma respiratory infections. Intranasal inoculation of M. pulmonis in mice and M. pneumoniae in hamsters results in pneumonia characterised by peribronchiolar and perivascular cuffing by lymphocytes. Thymus-dependent lymphocytes were depleted in mice by thymectomy and X-irradiation or treatment with anti-lymphocyte serum (ALS), and in hamsters by treatment with ALS. These procedures caused a reduction in the severity of pneumonic lesions in infected animals compared with infected immunologically normal animals. In addition, the organisms were present in slightly greater numbers in the lungs of the immunosuppressed animals. These results indicate the importance of thymus-dependent lymphocytes in the pathogenesis of mycoplasma-induced pulmonary disease. However, the role that these cells play in resistance to infection is not known and it may be that local secretory antibody is also important. Results of preliminary experiments involving hamster tracheal organ cultures infected with M. pneumoniae indicate that there is a factor present in lung washings from immune hamsters that protects against loss of ciliary activity brought about by M. pneumoniae.


Hemobilia following percutaneous liver biopsy. A patient underwent a routine percutaneous liver biopsy and subsequently developed gastrointestinal hemorrhage, biliary colic, and bilirubinuria suggesting the presence of hemobilia. After a negative arteriogram endoscopic cholangiography was used to confirm the diagnosis.