Transient cerebral dysfunction following chemotherapy for osteogenic sarcoma. An unusual neurological syndrome occurred in 4  of 158 patients treated for osteogenic sarcoma with combination chemotherapy. There was an abrupt onset of focal cerebral deficits approximately ten days after chemotherapy with vincristine and high-dose methotrexate plus citrovorum factor rescue. The syndrome was short lived and always occurred early in the course of treatment. Prolonged neurological deficits remained in 2 patients. When similar chemotherapy was reinstituted in the 4 patients, no further neurological complications ensued. Possible causes include a leukoencephalopathy related to methotrexate or an embolic cerebral vasculopathy related to necrotic tumor microemboli emanating from the lungs.


Clavulanic acid, a novel inhibitor of beta-lactamases. Clavulanic acid, Z-(2R,5R)-3-(beta-hydroxyethylidene)-7-oxo-4-oxa-1-azabicyclo-[3,2,0] heptane-2-carboxylic acid, has been shown to be an effective inhibitor of the beta-lactamases of the Richmond types II, III, IV, and V. Inhibition is a time-dependent reaction and is irreversible. Clavulanic acid had poor antibacterial activity against Staphylococcus aureus, Enterobacteriaceae, and Pseudomonas aeruginosa, with minimal inhibitory levels greater than 25 mug/ml. It did inhibit the majority of Neisseria gonorrhoeae at 0.1 mug/ml and Haemophilus influenzae at 6.3 mug/ml. Clavulanic acid acted synergistically with penicillins and cephalosporins to inhibit beta-lactamase-producing S. aureus and Enterobacteriaceae. Clavulanic acid combined with ampicillin inhibited beta-lactamase-producing N. gonorrhoeae, H. influenzae, Escherichia coli, Salmonella typhi, and Shigella sonnei.


Beta-lactamase production and resistance to beta-lactam antibiotics in Nocardia. Although ampicillin has been suggested as a useful agent for the treatment of nocardiosis in man, little is known regarding the presence of beta-lactamase in Nocardia or its possible role in determining resistance to ampicillin and the other beta-lactam antibiotics. We have evaluated 55 isolates of Nocardia for susceptibility to five beta-lactam antibiotics and for the presence of beta-lactamase. Nocardia were resistant to penicillin G, cloxacillin, and cefazolin, but 27 and 62% were susceptible to 3.1 and 25 mug of ampicillin per ml, respectively. Almost 90% of these ampicillin-susceptible or intermediate strains were also susceptible to carbenicillin. The combination of ampicillin and cloxacillin was synergistic against many ampicillin-resistant strains. Beta-lactamase was detected in 89% of Nocardia isolates when intact cells were used and in six of six strains after cell fractionation. This beta-lactamase was most active against penicillin G and ampicillin, with lesser activity against carbenicillin and cephaloridine. These studies suggest that beta-lactamase may be present in all clinical isolates of Nocardia and that mechanisms of antimicrobial resistance other than or in addition to beta-lactamase are responsible for resistance of Nocardia to ampicillin and carbenicillin.


Minimum bactericidal concentration of sulfamethoxazole-trimethoprim for Haemophilus influenzae: correlation with prophylaxis. The inability of sulfamethoxazole-trimethoprim (SXT) to eradicate Haemophilus influenzae nasopharyngeal carriage in all asymptomatic patients in closed populations was examined in vitro. A broth medium was adapted for susceptibility testing of H. influenzae which permitted us to determine minimum inhibitory concentrations and minimum bactericidal concentrations (MBCs). The minimum inhibitory concentrations were all low, but the MBCs were bimodally distributed. Trimethoprim alone or the combination SXT either was bactericidal for H. influenzae isolates at low concentrations (i.e., low MBCs) similar to minimum inhibitory concentrations or showed no bactericidal activity (i.e., high MBCs). If trimethoprim was bactericidal when tested alone against H. influenzae, then the combination SXT was also bactericidal. H. influenzae carriage could not be eradicated from asymptomatic patients with SXT therapy when that combination was not bactericidal for these isolates in vitro. H. influenzae carriage was eradicated from patients when the activity of SXT was bactericidal in vitro. H. influenzae strains that are not killed by trimethoprim or SXT seem to occur at random.


Treatment of spasmodic torticollis by dorsal column stimulation. A new method is described to treat spasmodic torticollis with the implantation of a dorsal column stimulator at the C1--2 level or with transcutaneous stimulation. 22 patients were evaluated. 3 had sufficient relief to be treated with transcutaneous stimulation only. An additional 6 patients had surgically implanted dorsal column stimulators. It was empirically determined that a frequency of 800--1,100 Hz gave the best relief from torticollis. 1 patient had an excellent result; 3 have had good results; 1 had a fair result, and 1 had a poor result. An additional patient with dystonia musculorum deformans was considerably improved by the use of dorsal column stimulation.


Electrical spinal cord stimulation for spastic movement disorders. Spinal cord stimulation seems today a promising method to improve spasticity. The experiences of two different clinics (Zürich and Freiburg i.Br.) are reported with long-term assessment up to 28 months. The objective data with measurement of stretch and H reflexes support the clinical results. An experimental study on animals does not permit a definitive explanation, but some hypotheses can be suggested.


Chronic paleocerebellar stimulation for the treatment of neuromuscular disorders. Four case report. 4 patients suffering severe neuromuscular diseases were subjected to a subtentorial implantation of electrodes over the anterior cerebellar lobe surface. Chronic stimulation was applied for 90 min to 7 h daily, with a rate of 20--180 Hz, 6--10 V and a schedule of 15 min "on", 15 min "off". Some improvement was observed in 3 patients treated with high frequency stimulation. 1 patient suffered seizures after three months of chronic stimulation. In 2 cases, posterior fossa explorations were necessary for revision of the stimulation apparatus and marked meningeal proliferation surrounding the electrodes was observed. Light and electron microscopic examination of the biopsies showed loss of Purkinje cells and gliofibrillar reaction. Effectiveness and side effects of chronic stimulation of the cerebellum are discussed.


Percutaneous central gray stimulation for cancer pain. Electrical stimulation of the periventricular and periaqueductal gray matter via a percutaneous electrode appears to be a useful method for relieving cancer pain with midline and bilateral distribution. Due to the nondestructive character and the minor surgical risks involved in this procedure it may be tried before considering bilateral cordotomy or myelotomy. A possible mechanism of action or at least a contributive factor to the pain relief is the activation of endorphins.


Subcutaneous transposition of the spleen: a method for treatment of complications in portal hypertension? Eleven patients with portal hypertension were treated with subcutaneous transposition of a resected spleen. In eight of the patients the operation was performed after variceal bleeding. In this group there was one operative mortality--a 77-year-old woman. Another patient died after 28 months in upper gastrointestinal bleeding. Autopsy showed varices in the gastric fundus and a cancer in the cardia. The other six patients are alive and in good health after 41--60 months. The operation was performed in another three patients, who had not bled. The indication was hypersplenism and esophageal varices in two and severe thrombocytopenia in one. Two of these patients (both with advanced hepatic disease) died postoperatively. The operation is proposed as an alternative method in the treatment of portal hypertension--especially when the main problem is hypersplenism. The operation has no negative effects on liver function and does not cause encephalopathy. Hypersplenism is cured. The survival time and freedom from postoperative bleeding among those who bled preoperatively is in the present material very satisfactory. However, the operation cannot be recommended for the prophylactic treatment of patients with esophageal varices who have not bled--at least not in the patient with advanced hepatid dysfunction.


Prompt endoscopic diagnosis of upper gastrointestinal hemorrhage: its value for specific diagnosis and management. From July 1, 1973 to June 30, 1976 789 patients admitted as upper gastrointestinal bleeders had endoscopies performed within 24 hours after preliminary resuscitation and preparation. More than one lesion was found in approximately 45% of the patients. Erosive hemorrhagic gastritis was the most common lesion, being present in 27.3--48.2% of the subjects (the latter precentage was found in those with a history of intake of both alcohol and ulcerogenic drugs). Gastric ulcer was the next most common lesion, present in 16.3--18.42%; the higher percentage represents the patients who were taking ulcerogenic drugs. The highest incidence of gastric ulcer (19.59%) or duodenal ulcer (10.5%) was among the patients in a group who had no apparent definite cause for the bleeding. A small number of patients had rare causes for the bleeding and in only a small percentage of the patients was the cause not diagnosed. These data suggest that early endoscopy is of diagnostic value in upper G.I. bleeders leading to prompt, lifesaving management and prevention of prolonged morbidity.


[Immune profile in melanoma patients. I. PHA--stimulation of circulating lymphocytes and number of T- and B-lymphocytes (author's transl)]. 20 patients with malignant melanoma in clinical stage I and II and 10 controls were examined by means of the PHA-lymphocyte-stimulation-test as by the sheep red cell rosette formation for T-cells and by the mouse red cell rosette formation for B-cells at the beginning of a non-specific immunotherapy with BCG. Mean values of both the PHA stimulation indices and the circulating T-cells and B-cells did not show any significant differences in patients with malignant melanoma compared to the control group. The relatively wide range of values was striking, especially in patients with malignant melanoma in clinical stage II. Thus cross-section studies concerning the immunology of patients with malignant melanoma are thought to be less evident for the clinician than immunologic studies of the course of disease in the individual patient.


Listeria endophthalmitis.

Listeria endophthalmitis. Listeria endophthalmitis developed in a patient who was being treated for extensive metastases of carcinoma of the breast. At the time of admission she was receiving cobalt therapy, chemotherapy, and high doses of oral steroids. The early identification of organisms with an immediate paracentesis and the early institution of broad-spectrum antibiotics is recommended.


Fusarium oxysporum endophthalmitis.

Fusarium oxysporum endophthalmitis. A 27-year-old man sustained a thorn injury to his left eye and a culture-proven Fusarium oxysporum endophthalmitis developed. This was successfully treated with a vitrectomy, intravitreal and intravenous amphotericin B, and oral flucytosine. The patient maintains 20/20 vision at this time in his left eye. We recommend combined therapy for this filamentous fungal infection.


Candida endophthalmitis after intravenous drug abuse. Patients with endogenous Candida endophthalmitis associated with intravenous (IV) drug abuse may manifest ocular and systemic signs different from those seen in other forms of endogenous Candida endophthalmitis. There may be a sparcity of evidence of systemic candidiasis, including negative serology and normal physical examination results. Anterior uveitis and extensive vitreous involvement are common and do not necessarily have associated typical retinal lesions, which are more commonly seen in the compromised host. This may occur either because of the more transitory nature of choroidal or retinal lesions or because these patients often seek treatment at later stages. Even with a typical clinical picture, it is difficult to get culture confirmation of the diagnosis. Material obtained by vitrectomy must be concentrated before inoculation of media because of the known difficulty of culturing Candida from the vitreous cavity.


Origin of the multiple components of human alpha1-antitrypsin. Multiple components of human alpha1-antitrypsin were separated by preparative starch gel electrophoresis, and the sialic acid contents of these components were determined. The acidic components contained more sialic acid per molecule than the basic components. The molecular sizes of these components were identical, excluding the possibility of polymerization of the inhibitor in the formation of the multiple components. Consequently, the multiple components of the inhibitor are primarily due to differences in the sialic acid content of each component. Three major components contain eight, seven, and six sialic acid residues per molecule, respectively.


Aerobic glycolysis and lymphocyte transformation. 1. The role of enhanced aerobic glycolysis in the transformation of rat thymocytes by concanavalin A has been investigated. Concanavalin A addition doubled [U-(14)C]glucose uptake by rat thymocytes over 3h and caused an equivalent increased incorporation into protein, lipids and RNA. A disproportionately large percentage of the extra glucose taken up was converted into lactate, but concanavalin A also caused a specific increase in pyruvate oxidation, leading to an increase in the percentage contribution of glucose to the respiratory fuel. 2. Acetoacetate metabolism, which was not affected by concanavalin A, strongly suppressed pyruvate oxidation in the presence of [U-(14)C]glucose, but did not prevent the concanavalin A-induced stimulation of this process. Glucose uptake was not affected by acetoacetate in the presence or absence of concanavalin A, but in each case acetoacetate increased the percentage of glucose uptake accounted for by lactate production. 3. [(3)H]Thymidine incorporation into DNA in concanavalin A-treated thymocyte cultures was sensitive to the glucose concentration in the medium in a biphasic manner. Very low concentrations of glucose (25mum) stimulated DNA synthesis half-maximally, but maximum [(3)H]thymidine incorporation was observed only when the glucose concentration was raised to 1mm. Lactate addition did not alter the sensitivity of [(3)H]-thymidine uptake to glucose, but inosine blocked the effect of added glucose and strongly inhibited DNA synthesis. 4. It is suggested that the major function of enhanced aerobic glycolysis in transforming lymphocytes is to maintain higher steady-state amounts of glycolytic intermediates to act as precursors for macromolecule synthesis.


A possible role for 5-hydroxytryptamine as a mediator for calcitonin actions on the gastrointestinal tract and pancreas in rats. Administration of pig calcitonin (10 M.R.C. units/kg body wt.) produced an immediate decrease in 5-hydroxytryptamine content in the antrum-duodenum region and ileum. In contrast, the hormone treatment rapidly increased the concentration of 5-hydroxytryptamine in the blood and pancreas. Serum immunoreactive gastrin did not change over a period of 3h after calcitonin administration. The results suggest that the release of 5-hydroxytryptamine probably mediates calcitonin actions on the gastrointestinal tract and pancreas.


Lack of correlation between in vivo rejection of syngeneic fibrosarcomas and in vitro non-specific macrophage cytotoxicity. Two transplantable, highly immunogenic syngeneic C57BL fibrosarcomas, FS1 and FS6, were shown to have tumour-specific rejection antigens, as shown by excision of the primary tumours and i.p. or i.m. injection of graded doses of the specific and unrelated tumour cells. I.p. challenge with tumour cells induced a large and relatively long-lasting increase in numbers of peritoneal leucocytes. Macrophage monolayers prepared from such exudates were, in general, non-specifically cytotoxic, though occasional specific cytotoxicity was detected. T lymphocytes isolated from exudates were shown to kill in a specific manner. When immunized mice were challenged with the specific tumour cells to elicit large numbers of peritoneal cytotoxic cells, and with graded doses of the non-cross-reacting tumour cells at the same time or at various times thereafter, growth of the non-related tumours occurred in all cases and only the specific tumour was rejected. Moreover, Winn tests, in which the inflammatory cells were mixed with unrelated tumour cells and implanted i.m., did not delay tumour growth. The relevance of these findings to the role of macrophages and lymphocytes in syngeneic tumour rejection is discussed.


E-rosette-forming cells at 29 degrees C: an assay for the evaluation of the immune status of cancer patients. High-affinity rosette-forming T-cell assays were performed by incubation of peripheral-blood mononuclear cells with sheep erythrocytes (E) at 29 degrees C. As compared with normal controls, the levels of high-affinity rosette-forming cells (RFC) were much more frequently depressed in cancer patients than were the total E-RFC incubated at 4 degrees C. Only 2/83 normal controls had less than 38% 29 degrees C E-RFC (mean 48 +/- 5), whilst 78/89 cancer patients were below this level. The few postoperative patients tested exhibited a normal range of 29 degrees C E-RFC. The 29 degrees C E-rosette assay gives reproducible counts of a T-cell subset, and is a sensitive assay for evaluating the immune status of cancer patients.


Cell studies in prolymphocytic leukaemia. A case of prolymphocytic leukaemia, showing several features not yet reported in this disease, is reported. The majority of lymphocytes in the peripheral blood and bone marrow had markers of both B- and T-lymphocytes. The simultaneous presence of receptors for sheep RBC and surface immunoglobulins on individual cells was demonstrated and the endogenous origin of these markers was established. The lymphocytes had some of the functional characteristics seen in chronic lymphocytic leukaemia (CCL). In vitro cell death in the presence of colchicine (colchicine ultrasensitivity) and polystyrene bead column retention were of the same order as seen in CLL. In contrast with the findings in CLL, these cells were markedly radioresistant in vitro. The dominant clinical features--anaemia and constitutional symptoms--appeared to be related to hypersplenism associated with massive splenomegaly. The relevance of these findings is discussed.


Homology of single copy and repeated sequences in chicken, duck, Japanese quail, and ostrich DNA. The extent of reassociation of 3H-labeled repetitive or single copy DNA sequences from the chicken with excess unlabeled DNA from the duck, the Japanese quail, and the ostrich, respectively, was measured by hydroxylapatite chromatography. Chicken repetitive DNA reassociated to an equal or greater extent than chicken single copy DNA with the DNA of each of the other birds. Using an isolated subfraction of chicken repetitive DNA representing those DNA sequences common to the chicken and ostrich genomes, we determined that many repetitive DNA sequences that occur at high repetition frequency in the chicken genome have a much lower repetition frequency in ostrich DNA. The data indicate that there has been a striking change in the number of copies of many repetitive DNA sequences during avian evolution.


Circular dichroism of chemically modified human plasma alpha1-antitrypsin. Interaction with porcine elastase. Chemical modifications of human plasma alpha1-antitrypsin with reagents which modify lysyl residues (citraconic anhydride, acetic anhydride, formaldehyde and 2,4,6-trinitrobenzenesulfonic acid) and arginyl residued (1,2-cyclohexanedione) were examined with regard to their effect upon the elastase inhibitory capacity of the glycoprotein. 2,4,6-Trinitrobenzenesulfonic acid was employed to quantitate the remaining free amino groups (epsilon-NH2 groups of lysine) and the extent of modifications. Amino acid analysis was utilized in the same capacity for the guanidino groups of arginyl residues. The elastase inhibitory capacity of alpha1-antitrypsin was destroyed following trinitrophenylation, citraconylation and acetylation. Circular dichroism of the native and modified derivatives revealed major changes in conformation following trinitrophenylation and citraconylation while CD profiles of acetylated and reductively methylated derivatives differed from that of the native profile considerably less. Reductively methylated alpha1-antitrypsin retained its elastatse inhibitory capacity. The reaction of 1,2-cyclohexanedione with alpha1-antitrypsin did not effect in a loss in inhibitory capacity. Gel filtration studies of native and modified alpha1-antitrypsin on Sephadex G-100 demonstrated an increased molecular weight presumably through molecular aggregation, in the citraconylated and trinitrophenylated derivatives, but not in the cases of the other derivatives. Based upon these studies and previous investigations of our laboratory, it was concluded that (1) alpha1-antitrypsin is a lysyl inhibitor type (i.e., the reactive site is a Lys-X bond), (2) its interaction with elastase follows a pattern similar to trypsin and chymotrypsin, and (3) the positively charged epsilon-NH2 group of lysine is essential for the maintenance of elastase inhibitory capacity.


The fucosyl specific lectins of Ulex europaeus and Sarothamnus scoparius. Biochemical characteristics and binding properties to human B-lymphocytes. From the seeds of the gorse, Ulex europaeus and of the broom, Sarothamnus scoparius L-fucosyl-specific lectins were isolated by affinity chromatography on L-fucosyl-epoxy-Sepharose. The lectins showed similarities in their molecular weights, amino acid composition, carbohydrate content and in the finger-prints of their tryptic peptides. The fluorescein-labeled lectins of both seeds attached especially to the plasma membranes of human B-lymphocytes.


Linear dichroism and the orientation of reaction centers of Rhodopseudomonas sphaeroides in dried gelatin films. Aqueous mixtures of reaction centers of Rhodopseudomonas sphaeroides and gelatin were dried to form thin films. Following hydration, these films were stretched as much as two to three times their original length. Polarized absorption spectra showing linear dichroism were obtained for both unstretched and stretched films, with the planes and stretching axes of the films mounted in various geometries relative to the electric vector of the measuring beam. These data were analyzed in terms of the following model: Reaction centers possess an axis of symmetry that is fixed in relation to the reaction center structure. In unstretched films this axis is confined to the film plane and oriented at random within the plane. In stretched films the symmetry axis is aligned with the direction of stretching. In both preparations reaction centers are distributed randomly with respect to rotation about the axis of symmetry. The data are consistent with this model when the analysis acknowledges less than perfect orientation. For perfect orientation in a stretched film the model predicts uniaxial symmetry about the axis of stretching. The approach to this condition was examined with films stretched to different extents. Extrapolation yielded dichroic ratios for the ideal case of perfect orientation, and allowed calculation of the angles between the axis of symmetry and the various optical transition dipoles in the reaction center. This treatment included the two absorption bands of the bacteriochlorophyll 'special pair' (photochemical electron donor) in the Qx region, at 600 and 630 nm, which we were able to resolve in light minus dark difference spectra.


The orientations of transition moments in reaction centers of Rhodopseudomonas sphaeroides, computed from data of linear dichroism and photoselection measurements. Linear dichroism measurements of reaction centers of Rhodopseudomonas sphaeroides in stretched gelatin films have yielded angles that various optical transition moments make with an axis of symmetry in the reaction center. Photoselection experiments have yielded angles that certain transition moments make with each other. We have combined these data so as to compute the orientations of the Qx and Qy transition moments of the two molecules of bacteriopheophytin and of the bacteriochlorophyll special pair (photochemical electron donor) in the reaction center. Orientations are expressed in spherical polar coordinates with the symmetry axis as the pole. We have also computed additional angles between pairs of transition moments. In this treatment we have assumed that the bacteriopheophytins are independent monomers with little or no exciton coupling.


Optical diffraction study of muscle fibers. II. Electro-optical properties of muscle fibers. When an electric field is applied along the fiber axis, the intensities of all observable optical diffraction lines of skeletal muscle fibers increase. This electro-optical effect was extensively studied and it was confirmed that the effect is due to the interaction between electric dipole moments of thin filaments and the applied field. From the present study on the intensity modulation due to applied field in sinusoidal and square forms, we confirmed that (1) the thin filament is a semiflexible rod, (2) the second order mode of the bending motion of thin filaments contributes to the electro-optical effect of muscle fibers at higher frequencies of a sinusodidal field or shorter durations of a square field, (3) the induced moment has no appreciable effect, and (4) the estimated value of the flexural rigidity of thin filaments strongly depends on the concentrations of free calcium ions in the myofibrillar space.


[Effect of acetylcholine on the firing rate and action potential shape of pacemaker cells]. A study was made of the action of exogenous acetylcholine on the isolated pacemaker of the Rana temporaria heart. Bioelectrical activity of individual cells and sum total activity of the preparation were recorded. Exogenous acetylcholine was found not only to inhibit, but also to accelerate the rhythm of pacemaker cells' discharge. As a rule, positive chronotropic effects were observed when relatively low acetycholine concentrations were used. Parasympathetic acceleration was accompanied by an increase in the rate of slow diastolic depolarization; this is in favour of the active mechanism of this process. It is suggested that low and high concentrations of acetylcholine could change the transmembrane ionic currents in a different way.


[Effect of thymectomy on induction of immunologic tolerance in adult mice and on the recovery of initial immunoreactivity]. The tolerance to sheep red blood cells induced with cyclophosphamide became more profound and prolonged in mice thymectomized before or after the tolerance induction. The greatest immunocompetence depression was achieved when the operation was preformed 24 hours before the tolerogenic treatment. The results obtained confirmed the assumption that this form of tolerance was due to deficiency of a definite T-helpers clones.


B-cell lymphoma lacking Fc- and C3d-receptors. Various cell surface markers were studied in a patient with lymphosarcoma cell leukemia. The B-cell derived feature of the neoplastic cells could be identified by demonstration of monoclonal surface immunoglobulin of IgM-kappa type of high density synthesized by the cells. Interestingly, there were no Fc- nor C3d-receptors demonstrable using various techniques. Only 22% of the leukemic cells expressed C3b receptors. The failure of rosette formation with mouse erythrocytes was an additional surface feature distinguishing from ordinary chronic lymphatic leukemia of the B cell type. The phenotype of the leukemia cells is discussed as corresponding to that of a less differentiated B lymphocyte.


DNA-synthesizing T and non-T cells in chronic lymphocytic leukemia. In 21 patients with chronic lymphocytic leukemia (CLL) and in 8 hematologically normal persons the number of DNA-synthesizing peripheral blood lymphocytes was investigated by autoradiographic techniques. The lymphocytes were differentiated by EN-rosette tests into T and non-T lymphoid cells. The results show a normal number of proliferating T lymphoid cells and an increased number of proliferating non-T lymphoid cells in clinical stages O-I. Stages III-IV demonstrate a significant increase of the proliferation rate of both T and non-T lymphoid cells. The possible pathogenetic factors and the prognostic value of these results are discussed.


[A variant of the von Willebrand-Jürgens-syndrome with abnormalities of the factor VIII/von Willebrand factor protein (author's transl)]. A family is reported with a variant of von Willebrand's disease. The members of this family showed a qualitative defect of the factor VII/von Willebrand factor protein. The qualitative defect was characterized by an abnormal electrophoretical mobility of factor VIII-related antigen and an abnormal elution pattern as demonstrated by gelfiltration on Sepharose 4 B. Factor VIII-subunits in these patients were found to be normal by polyacrylamidgelelektrophoresis.


Inhibition of 5,7-dihydroxytryptamine-induced supersensitivity to 5-hydroxytryptophan in mice by treatment with cycloheximide. Intracisternal injection  of 5,7-dihydroxytryptamine (5,7-DHT) following treatment with desmethylimipramine induced development of behavioral supersensitivity to the intraperitoneally administered serotonin precursor 5-hydroxytryptophan (5-HTP) in the mouse. This behavioral syndrome, characterized by tremor and muscle twitches (myoclonus), showed a clear dose-response relationship with 5,7-DHT as well as with 5-HTP. Mice lesioned with a low dose of 5,7-DHT (20 micrograms) or a placebo were treated repeatedly with a protein synthesis inhibitor, sycloheximide (45 mg/kg, s.c., every 12 h for up to 10 days). This treatment resulted in a reversible decrease of cerebral protein synthesis varying between 70 and 20% with time between treatments. The myoclonic response to 5-HTP in animals pretreated with 5,7-DHT and by cycloheximide showed a decrease in intensity within 24 h when evaluated quantitatively by an electronic activity monitor, the results of which were confirmed by direct observation. Cycloheximide also exerted a similar, though smaller, effect following full development of sensitivity to 5-HTP over 10 days. These effects may de mediated by inhibition of rapidly turning over serotonin receptor proteins, although their interpretation is somewhat obscured by possible toxic effects of cycloheximide.


Anaesthetic management for coronary artery bypass surgery. The principles and practice of aneasthesia for patients having coronary bypass grafts are discussed. The essential basic principle is to restrict myocardial oxygen requirement while maintaining oxygen supply. The pathophysiology of coronary artery disease and the pharmacological principles for successful management of the cardiac patient through operation and whole body perfusion for coronary bypass grafts are summarized.


Immunological monitoring during chemotherapy for advanced Hodgkin's disease. A study of some immunologic in vitro and in vivo changes during the course of chemotherapy in 17 cases of advanced Hodgkin's disease was made. Skin testing with PPD, candida albicans and streptodornase antigens was studied together with studies of B and T cell numbers in the blood and responses to migration inhibition testing for PPD and PHA. An excellent correlation was found between recovery of normal immunologic responses and clinical remission despite the use of immunosuppressive chemotherapy.


A study of surface markers in acute lymphocytic leukemia by using anti-T and anti-B lymphocyte sera. Cell surface markers of 21 cases of acute lymphocytic leukemia (ALL) were studied with various surface markers, especially by using anti-human B lymphocyte serum (ABS), anti-human thymocyte serum (ATS-T) and anti-human peripheral T lymphocyte serum (ALS-T) which were rendered specific for human B lymphocytes, human thymocytes and human peripheral T lymphocytes. The proportion of cell types in ALL was null cell leukemia 38%, B cell leukemia 38% and T cell leukemia 24%, respectively. T-ALL cells were reactive to ATS-T but not to ALS-T, a fact which suggests their thymic origin. It should be noted that these anti-lymphocyte sera detected T or B marker antigens, even when other markers showed negative. Twelve patients with ALL were also investigated from their clinical pictures. Patients with B cell leukemia had severe signs of anemia and a higher grade of hepato-splenomegalies than other types in ALL. Patients with T cell leukemia were in older age levels and had a poorer prognosis.


Peripheral T lymphocytopenia under exogenous thermal stress. A transient decrease in T lymphocytes in peripheral blood was observed in twelve healthy volunteers immersed in hot water baths which raised their mean rectal temperature by 1.35 C. T lymphocytes declined from 59 to 41 rel % (2p less than 0.001) or from a mean of 1990 to 1300 per mm3. T lymphocytopenia was accompanied by a relative increase in the fraction of B lymphocytes. Total lymphocyte count remained unchanged. In vitro heating alone to 39 C did not influence the total of SRBC-labelled lymphocytes. The findings are interpreted to be the result of a change in lymphocyte distribution with increased recirculation of mobile T lymphocytes.


Small lymphocyte T-cell leukemia in the adult. A 49-year-old man is described with morphologic T cell chronic lymphocytic leukemia, whose clinical course, however, progressively deteriorated with central nervous system involvement, resistance to treatment and death within eight months. In addition to widespread organ invasion by leukemic cells there was depression of cellular immunity. The leukemic lymphocytes showed an aberrant response to mitogens, and despite undetectable Ia-like surface antigens were able to stimulate allogeneic cells in the mixed leucocyte reaction. From this and similar cases reviewed herein, it appears that the syndrome of small T-lymphocyte leukemia of the adult is a rapidly aggressive and resistant disease with characteristic clinical and laboratory findings.


Restorative effects of levamisole on cell-mediated immune responses following chemotherapy with aniline mustard in mice bearing ADJ-PC5 plasmacytoma. Restorative effects of levamisole on general and tumor-associated cell-mediated immune responses were investigated following aniline mustard (AM) chemotherapy of BALB/c mice bearing ADJ-PC5 plasmacytoma. Total eradication of tumor following AM chemotherapy resulted in severe depression of lymphoproliferative (LP) responses which recovered after a prolonged period of 4-6 weeks. During this time, spleen cells from these treated mice were shown to be generally depressed to T- and B-cell mitogens. Levamisole, an anthelmintic drug capable of enhancing depressed immune responses in mice and in man, was employed following AM chemotherapy in an attempt to restore immunocompetency. Administration of levamisole following AM had a significant effect on the ability of mice to resist rechallenge with ADJ-PC5 tumor and in tumor cell neutralization. The enhanced resistance to tumor cell challenge appeared to be associated with a faster recovery of the general T-cell immunocompetence as demonstrated in the LP assays among the mice receiving chemotherapy followed by adjuvant therapy. Levamisole, when administered alone to tumor-bearing mice, did not appear to possess a direct antitumor effect. In addition, levamisole did not potentiate cellular immunity to higher than normal levels in nonimmunodepressed mice. These results demonstrate the efficacy of levamisole as a restorative agent of the general and tumor-associated immunocompetency in the immunodepressed host.


Effects of combined immunotherapy with levamisole and Bacillus Calmette-Guérin on immunocompetence of patients with squamous cell carcinoma of the cervix, head and neck, and lung undergoing radiation therapy. Patients with squamous cell carcinoma of the head and neck, squamous cell carcinoma of the cervix, and lung carcinoma were treated with radiation therapy (RT) prior to being randomly assigned either to a group receiving no further treatment or to a group treated with combined adjuvant immunotherapy (bacillus Calmette-Guérin and levamisole). A battery of in vitro immunologic evaluations in addition to skin tests was used to evaluate these patients prior to RT, immediately following RT, and at regular intervals thereafter. Mean percentages and levels of circulating T lymphocytes were significantly lower in all three types of patients prior to RT than in normal healthy controls. B-lymphocyte percentages and levels, however, were not significantly different from controls except for lower B-cell levels in the lung group. Following completion of RT, circulating levels of both T and B lymphocytes were significantly lower than pretreatment values although the percentages were not significantly changed. Mitogenic responses of patient lymphocytes to both phytohemagglutinin and pokeweed mitogen were significantly lower prior to RT than were healthy control responses. A further depression of blastogenesis following RT was statistically significant. Preliminary data at intervals following RT indicate a gradual recovery of depressed immune parameters (T- and B-lymphocyte levels and mitogenic responses) both in patients treated with adjuvant immunotherapy and in those receiving no further treatment. Although not statistically significant in preliminary data, there is a suggestion that recovery of these immune parameters is slower in the group receiving immunotherapy. Plasma sialic acid levels were elevated in patients when compared to healthy controls and remained elevated throughout the study with little fluctuation. Lymphocyte cytotoxic activity against tumor target cells was variably affected by RT, but was generally increased at 8 weeks following RT when compared to previous values.


In vitro induction of Lyt surface markers on precursor cells incubated with thymosin polypeptides. Induction of precursor T cells by thymosin fraction 5 was found to generate a population of cells bearing the Lyt 1+, 2+, and 3+ phenotype and functionally capable of providing T-cell helper activity in vitro. However, when the component polypeptides of thymosin fraction 5 were similarly analyzed, several displayed inductive activities quite different from those of the parent preparation. These results suggest that variations in the polypeptide composition determine, to a large part, the inductive properties of a thymosin preparation and that such variations in vivo may serve as a regulatory system for T-cell maturation.


Control of differentiation of thymocyte precursors in the bone marrow by thymic hormones. Terminal deoxynucleotidyl transferase (TdT) is uniquely associated with the major thymocyte population and a minor bone marrow population which is separable on bovine serum albumin gradients. The expression of TdT in the bone marrow subpopulation is under thymic regulation in that this population is significantly reduced in nude mice or is lost with time after thymectomy. The expression of TdT in athymic mice can be induced both in vivo and in vitro by thymosin fraction 5 or by beta3, a peptide purified from thymosin fraction 5. The optimal concentration of beta3 in the in vitro induction of TdT is approximately 10 ng/ml. These results demonstrate that thymic hormones control the early differentiation of prothymocytes in the bone marrow.


Characterization of thymosin-responsive peripheral blood null cells. Suspensions of human peripheral blood lymphocytes were enriched for E rosette-negative (E-) surface immunoglobulin-negative (SIg-) "null" cells expressing either human T or human B lymphocyte antigens. These enriched suspensions were then tested for responsiveness to activation of E rosette formation by thymosin. Thymosin activated some human T lymphocyte antigen-positive E-SIg- but not human B lymphocyte antigen-positive E-SIg- cells to form E rosettes. Therefore, thymosin-responsive peripheral blood null cells appear to be precommitted to the T- cell line of differentiation.


Thymosin-inducible lymphocytes in the peripheral blood of patients with malignant melanoma. E rosette-forming (T) lymphocytes and surface immunoglobulin-bearing lymphocytes were estimated in 85 patients with malignant melanoma. The melanoma patient group had lower mean levels of T lymphocytes and higher mean levels of immunoglobulin-bearing (? B) lymphocytes than did normal subjects. The absolute and percentage depressions of T-cell levels in the melanoma patients were stage-related, as was the depression of total lymphocyte and B-lymphocyte levels. The T lymphopenia in the melanoma patients could, in vitro, be partially abolished by fetal calf serum (as used in many E rosetting methods), and could be totally abolished by thymosin fraction 5 (Hoffmann-La Roche) at optimum concentration. In view of the ability of thymosin to restore T cells to normal levels in all of the T-lymphopenic patients, a clinical trial of this hormone in selected melanoma patients of all stages appears to be warranted.


Effect of maleic anhydride-vinyl ether on the lymphocyte subpopulations of tumor-bearing, irradiated mice. The splenic T- and B-lymphocyte populations of BALB/c mice were determined in Madison lung carcinoma 109-bearing animals. Concurrently, some groups of tumored mice were exposed to 500 rads of whole-body irradiation and were treated with one dose of maleic anhydride-vinyl ether (MVE). By direct immunofluorescence, it was found that the percentage of splenic T lymphocytes was significantly depressed in the tumored-irradiated mice. Mitogenic studies revealed that the T lymphocytes were more depressed in the tumored-irradiated mice than in the corresponding nonirradiated tumored mice. MVE was relatively effective in reconstituting the T-cell compartment of these splenic T lymphocytes. The B-cell compartment of the splenic lymphocytes of the tumored-irradiated mice was found to be extremely radiosensitive. Utilizing a specific anti-B serum, no B lymphocytes were detected during the testing. Blastogenic studies using lipopolysaccharide as the mitogenic probe revealed that the incorporation of 3H-TdR of the tumored-irradiated mice was just slightly higher than background values. MVE proved to be relatively ineffective in reconstituting the splenic B cells of the tumored-irradiated mice.


Lymhocyte stimulatory effect of an ether-extracted preparation of Brucella abortus. The effect of a Brucella abortus preparation (Bru Pel) on the T- and B-lymphocyte populations is described. Bru Pel treatment of tumor-bearing mice resulted in a slight reduction in tumor size, marked splenomegaly, and statistically significant reductions in the percentages of splenic T and B lymphocytes relative to untreated tumor controls. Bru Pel was also found to cause increases in the incorporation of 3H-thymidine of phytohemagglutinin-sensitive splenic T lymphocytes and lipopolysaccharide-sensitive splenic B lymphocytes over 3H-thymidine-incorporated values for untreated tumor controls.


Non-ependymal cilia in the habenulae and the interpeduncular nucleus of the frog tadpole. Cilia of the 9 + 2  pattern are found electron microscopically in nonependymal cells of the habenulae and the interpeduncular nucleus of the tadpole of Rana esculenta at an early stage of development (8 mm length, head to tip of tail). A comparison is made between these and the ependymal and sensory cilia in the same specimens. The cilia project into the neuropil emerging from a perikaryon rich in free ribosomes and displaying a prominent Golgi apparatus. These perikarya contain dense core vesicles. Synapses with vesicles of the clear spherical type have been observed along the ciliary shaft. On a purely morphologic basis the authors hypothesize that these cilia, at least in this early ontogenetic stage, may extend considerably the conducting surface of the cell and represent a sensory structure which could be stimulated by terminal processes belonging to distantly located cells. In addition, they could also be involved in the trophic exchange of material with the adjacent structures.


Viruses in water.

Viruses in water. Attention is drawn in this paper to the increasing problem of viral contamination of water and shellfish, particularly since growing demands for available water resources by a rising world population and expanding industry will make the recycling of wastewater almost inevitable in the future. The problem of eliminating viruses pathogenic for man from water is considered in the light of present water treatment procedures, which are often inadequate for that purpose. Man may be exposed to waterborne viruses through the consumption of contaminated water, shellfish, or crops, as a result of recreational activities involving water, or from aerosols following the spraying of crops with liquid wastes. Physical and chemical methods of eliminating viruses from water are discussed.


The effects of psychotropic drugs in different populations. Although psychotropic drugs are known to be effective in all populations, the known differences in terms of health and disease in different parts of the world have not been related to the effectiveness of such drugs. Nutritional/metabolic, genetic, cultural, and ecological/climatic factors that could be important in this respect are discussed. The benefits that could accrue from a knowledge of proper drug dosage, namely, fewer side effects and reduction in cost, particularly for developing countries, are highlighted.


Hypovitaminosis A and its control.

Hypovitaminosis A and its control. Hypovitaminosis A is considered to be the most common cause of blindness in the developing countries but it is not possible to estimate the prevalence of keratomalacia directly attributable to it. Subclinical hypovitaminosis A is not measurable at present in human subjects, but studies in animals indicate that the possibility of subclinical effects should not be ignored. The recommended procedure for identifying the "at risk" population involves a three-part survey to evaluate dietary intake, biochemical indices, and clinical signs. This article examines all three approaches in some detail, but in the present state of knowledge, none of them gives a satisfactory estimate of vitamin A status. For community assessment, the article discusses preliminary experience with a predictive model of the number of children in a population at risk of hypovitaminosis A that is based on associations noted repeatedly between protein-energy malnutrition and certain child-rearing practices, family economics, and morbidity. Criteria have been established for deciding on the need for a programme of prevention and the types of programme most appropriate in different situations are discussed. The methods of programme evaluation must take into account the stated objectives of the programme.


Rheumatic fever and rheumatic heart disease in developing countries. Studies on the prevalence and other epidemiological features of rheumatic fever and rheumatic heart disease and pilot prophylactic programmes have been carried out in India for the past 12 years or more. The results of these, together with data from other developing countries, have been taken into account in discussing the problems of these diseases in the developing world. Suggestions for their control, to be modified according to local conditions, are made.


Mixing of Schistosoma haematobium strains in Ghana. In Ghana, Schistosoma haematobium exists as two strains, one transmitted by Bulinus rohlfsi and the other by B. globosus. In Anyaboni, a resettlement town, where the field station of the UNDP/WHO Schistosomiasis Research and Control Project is located, the residents contract the "rohlfsi" strain of the parasite from the Volta Lake and the "globosus" strain from a stream near the town. The present studies indicate that there is mixing of the two parasite strains on a community and an individual basis. In Anyaboni, the parasite developed well in both B. rohlfsi and B. globosus. In another village 25 km from Accra, where B. globosus was the only vector, the parasite developed well in B. globosus but was refractory in B. rohlfsi. In a village near the Volta Lake where B. rohlfsi was the sole vector, the parasite developed well in B. rohlfsi but was refractory in B. globosus. However, complete separation of the two strains is uncommon in Ghana because extensive mixing has already occurred owing to migration of people and snails.


Preparation and laboratory testing of plain and aluminum hydroxide-adsorbed cholera vaccines used in a field trial in Indonesia. TWO TYPES OF CHOLERA VACCINE WERE PREPARED: a plain vaccine and an aluminium hydroxide-adsorbed vaccine, by using the Inaba NIH 35A3 and Ogawa NIH 41 serotypes of Vibrio cholerae. For cultivation, a solid medium was used and the cultures were inactivated with 0.02% thiomersal and by heating for 1 hour at 56 degrees C. The final vibrio concentration of the vaccines was adjusted to 16 x 10(9) vibrios/ml (equal proportions of the two serotypes). The antigenicity of the vaccines was assessed by the active mouse protection test and by the antibody production test, i.e. by determinating the vibriocidal antibodies in the sera of immunized mice. The results of the active mouse protection test showed that the antigenicity of the Inaba and Ogawa components of both vaccines met the WHO Requirements. The antigenicity of the Inaba component of both vaccines was about the same. The antigenicity of the Ogawa component of the plain vaccine appeared to be somewhat higher than that of the adsorbed vaccine. In the antibody production test, the adsorbed vaccine elicited a higher and longer-lasting immune response than the plain vaccine.


The use of cycloheximide-treated cells for isolating trachoma agents under field conditions. Standard procedures for the isolation of Chlamydia trachomatis require pretreatment of the tissue culture cells. We evaluated the use of cycloheximide, an antimetabolite that can be added to the cells with the inoculum. Cycloheximide-treated cells provided a sensitive system for isolating trachoma agents. This system was applicable to field studies as requirements for equipment were minimal and the cells were 2 weeks old when inoculated.


Early detection of antigen and estimation of virus yield in specimens from patients with Marburg virus disease. Autopsy specimens from patients with Marburg disease having at least 10(4.5) TCID(50) of virus per gram of tissue were found to contain sufficient fluorescent antigen-positive cells to make a specific diagnosis possible in less than 3 h. Liver, heart, spleen, and kidney tissues were found to contain significant amounts of virus. Tissue suspensions, as well as blood or serum samples, inoculated into Vero cell cultures produced virus-specific immunofluorescence within 2-5 days. At least one specimen of all virus-positive persons yielded Marburg virus-specific antigen on day 2 or 3 after inoculation. Furthermore, tissues with at least 10(5.5) TCID(50) of virus/g had Marburg antigen of sufficient titre to be used in complement fixation tests.


Poliomyelitis: Epidemiology and prophylaxis. 6. Geographic synchronism in poliomyelitis epidemics in Kenya. In the 1950s, van Loghem drew attention to what he called "synchronism" in the epidemics of poliomyelitis in western Europe. The 1952 epidemic in the Netherlands affected Belgium and neighbouring parts of the Federal Republic of Germany at the same time. A comparable phenomenon is described from Kenya. Notwithstanding the fact that in the three population concentrations of the country the three poliovirus types may well be endemic, epidemics of poliomyelitis repeatedly occurred synchronously in these areas. However, there seems to be no synchronism between poliomyelitis epidemics in Kenya and those in neighbouring East African countries. Tentative explanations are put forward for the similarities and differences between Europe and East Africa. The importance of the phenomenon as observed in Kenya for control by mass immunization campaigns is stressed.


Quality control in laboratory investigations on Schistosoma mansoni in St. Lucia, West Indies. Maintenance of artificial prevalence as a laboratory aid. A method is described of maintaining an apparent S. mansoni prevalence rate of 10% in an area estimated to have a natural rate of below 5% following two chemotherapy campaigns. To sustain interest and therefore accuracy among microscopists engaged on screening, known S. mansoni-positive stools were seeded, without their knowledge, among those collected in the field. The problems of achieving a desired level of seeding, and of a possible further dimension of the scheme are discussed.


A field test for detecting iodine-enriched salt. One of the most effective and well-established methods for the prevention of endemic goitre is the enrichment of table salt with appropriate amounts of iodine. A simple field test has been developed by which anyone, without special chemical training, can verify whether a sample of table salt has been enriched with iodine as required by local health regulations. Since all the equipment needed can conveniently be assembled as a small portable kit, the proposed method, which is highly sensitive, is appropriate for health workers in areas prone to endemic goitre.


Reutilization of 125I-labelled anti-IgE antibody and paper discs in PRIST and RAST IgE determination. In the paper radioimmunosorbent test (PRIST) anti-human IgE coupled paper discs are used for the estimation of total IgE in blood serum: in the radioallergosorbent test (RAST) allergen-coupled paper discs are used for the estimation of specific IgE in blood serum. The bound IgE or specific IgE is quantified by a 125I-labelled anti-human IgE. The non-bound 125I-labelled anti-human IgE can be collected and used in new assay. By a 4-h incubation of the used paper discs with 1 M glycine-HCl buffer (pH 2.7) the IgE-labelled anti-IgE complex can largely be removed. The paper discs treated in this manner can be used in a new assay.


The concentration of alpha-1-antitrypsin in cerebrospinal fluid and serum in a series of 40 intracranial tumors. Forty patients with histologically proved intracranial tumors were submitted to preoperative lumbar and venous punctures. The concentration of alpha-1-antitrypsin in the serum and in cerebrospinal fluid was determined by radial immunodiffusion technique. In the series, both serum and cerebrospinal fluid alpha-1-antitrypsin concentrations are significantly higher than the mean normal values. No statistical differences are observed in serum alpha-1-antitrypsin levels between benign and malignant tumors, but cerebrospinal fluid alpha-1-antitrypsin is significantly increased in the group of malignant tumors if cases undergoing steroid treatment are excluded. The diagnostic value of alpha-1-antitrypsin determinations in groups of patients with intracranial tumors is suggested.


alpha1-Antitrypsin deficiency in twins and parents-of-twins. Serum-trypsin-inhibitory-capacity (STIC) and alpha1-antitrypsin (AAT) genotypes were evaluated in 83 twins and 112 paired parents-of-twins. An increased prevalence (17.0--21.9%) of intermediate AAT deficiency (STIC less than 0.95 units/ml) was detected in both of these groups as compared to a prevalence of 4.1% in 1,841 healthy controls. PiS and PiZ molecular variants of AAT were also found more frequently in the twin and parent groups, but this was not statistically significant. Low levels of protease inhibition may enhance fertility and a tendency towards twinning, since proteolytic enzymes are involved in fertilization of ova by sperm and in gametogenesis. Increased fertility and twinning may be heterozygous advantages for AAT deficiency.


Isolated congenital ectopia lentis with autosomal dominant inheritance. Although autosomal dominant inheritance of isolated ectopia lentis has been described, the literature contains old and unclear reports concerning the evaluation of skeletal or metabolic abnormalities. We report a family in which congenital isolated ectopia lentis occurs in five members of two generations in a pattern consistent with autosomal dominant inheritance.


Adult Haemophilus influenzae type B vertebral osteomyelitis: a case report and review of the literature. Osteomyelitis in adults due to Haemophilus influenzae is exceedingly rare. We report a case of H. influenzae type b vertebral osteomyelitis in an adult. Review of the English literature reveals one other adult patient with H. influenzae osteomyelitis, and sporadic pediatric cases. Although a variety of predisposing host resistance factors have been postulated to account for this infection, the deficiency responsible for adult infection remains undelineated. Bone biopsy is mandatory for diagnosis when blood cultures are negative. The isolation and identification of H. influenzae may be delayed because of its fastidious growth requirements. Treatment with ampicillin or chloramphenicol appear to be most efficacious considering the antibiotic sensitivities of the organism.


Management of acute pain in trauma.

Management of acute pain in trauma. In acute pain, TENS, ice packs, and a calm, reassuring attitude and voice are useful in reducing pain. Narcotic requirements can be reduced, and chronic pain may be prevented. Complications such as paralytic ileus and atelactasis can also be reduced. These techniques can be used in the emergency ward, the recovery room, and the doctor's office.


Experience with a Fourier method for determining the extracellular potential fields of excitable cells with cylindrical geometry. In this chapter, well-known solutions that utilize a Fourier transform method for determining the extracellular, volume-conductor potential distribution surrounding elongated excitable cells of cylindrical geometry are reformulated as a discrete Fourier transform (DFT) problem, which subsequently permits the volume-conductor problem to be viewed as an equivalent linear-filtering problem. This DFT formulation is fast and computationally efficient. In addition, it lends itself to the application of some rather well-known techniques in linear systems theory (e.g., the DFT for convolution and least mean-square (Wiener) filtering for optimal prediction of a signal in random noise). Two specific examples are employed to demonstrate the utility of this discrete Fourier method: (1) the single, isolated, active nerve fiber in an essentially infinite volume conductor and (2) the isolated, active nerve trunk in a similar type of extracellular medium. In each of these, our DFT method is employed to obtain both the classical "forward" and "inverse" potential solutions for each volume conductor problem. In the case where the single, active nerve fiber is the bioelectric source in the volume conductor, simulated action-potential data from an invertebrate giant axon is utilized, and potentials at various points in the extracellular medium are calculated. The calculated potential distributions in axial distance z, at various radial distances r, are consistent with well-known experimental fact. When the active nerve trunk acts as the bioelectric source, the DFT method provides calculated potential distributions that are fairly consistent with experimental data under a variety of experimental conditions. For example, in these experiments, a special, isolated frog spinal cord preparation is used that permits separate or combined stimulation of the motor and sensory nerve fiber components of the attached sciatic nerve trunk. By manipulating the stimulus intensity applied to the motor (ventral) or appropriate sensory (dorsal) roots of the spinal cord, a variety of multiphasic extracellular volume-conductor potentials can be recorded from the sciatic nerve. The excellent agreement of model-generated and experimental data, regardless of the complexity of surface potential waveform, tends to validate the modeling assumptions and offer encouragement that this computationally efficient DFT method may be usefully employed in volume-conductor problems where both the bioelectric source, and the surrounding volume conductor, are of a much more complicated nature.


Serum immunoglobulin levels and tissue antibodies in psoriasis. Serum samples from psoriatic patients were subjected to quantitation of serum IgA, IgG and IgM levels and screening of tissue autoantibodies including ANA, GPA, MTA and SMA. Serum IgA was found to be significantly elevated and incidences of ANA and GPA were also increased. Their significance and possible mechanism were discussed.


The desaturated panel D-15.

The desaturated panel D-15. The Desaturated Panel D-15 is analogous in design to the standard Panel D-15 but of lower purity (chroma 2 Munsell); the test is more sensitive to mild and moderate losses in chromatic discrimination ability. Combination of the results of both tests allows recognition of several degrees of chromatic discrimination loss.


The new color test.

The new color test. The New Color Test allows estimation of the neutral zone (separation phase) and the characteristic color confusions (classification phase) using Munsell colors. The width of the neutral zone is estimated by the ranges of hues confused with grey. The severity of chromatic discrimination loss for a given axis is estimated by the range of chromas confused with grey.


[Prolymphocytic leukaemia (author's transl)]. Prolymphocytic leukaemia occurred in two women aged 75 and 57 years, respectively. In both instances the lymphatic cells fulfilled the morphological criteria of the disease picture. In one patient the disease was characterised by immunological and physical methods as being a B-cell lymphoma, in the other a T-cell lymphoma. Acid phosphatase was of special significance among cytochemical studies. While the patient with the T-cell lymphoma died after three months, the one with B-cell lymphoma is still alive 16 months later. Splenectomy resulted in marked improvement in the latter patient's condition and may turn out to be the treatment of choice in prolymphocytic leukaemia.


[Analgetic and anti-inflammatory action of glaucine]. The authors examined the analgetic and antiinflammatory action of glaucine. They used the following methods for evaluation the analgetic action: chemical irritation, heating plate, heat-ray irritation, mechanical irritation of the normal and inflammatory tissues, electrical irritation and analgetic test. The following methods were used for evaluation of antiinflammatory action: effect on the edema of the rat paw and granulation phases of the inflammation in rats. Codeine and acetysal were used as control drugs. The results from the experiments showed that glaucine successfully inhibited the granulation phase of inflammation and did not affect edema of the rat paw, induce by yeast beer. The analgetic action of glaucine was weak and without practical significance.


Specific binding of poly(I)-poly(C) to the membrane of murine B lymphocyte subsets. Indirect immunofluorescence revealed that 13% of BALB/c and 33% of CBA spleen cells of B type carry specific binding sites at their surface for double-stranded poly(I).poly(C). Pretreatment of BALB/c spleen cells with anti-mouse immunoglobulin serum increased the number of B cells capable of binding poly(I).poly(C) indicating the existence of a second B lymphocyte subpopulation carrying masked poly(I).poly(C)-binding sites. Pretreatment of the cells with mitogenic doses of either lipopolysaccharide (LPS) or single-stranded polynucleotides, e.g. poly(I) or double-stranded poly(A).poly(U), failed to affect binding of poly(I).poly(C) to the cells. Poly(I).poly(C) converts small poly(I).poly(C)-binding lymphocytes into lymphoblasts carrying poly(I).poly(C)-binding sites. Lymphoblasts derived from LPS-stimulated cells do not carry poly(I).poly(C)-binding sites. Thymocytes or splenic T cells failed to bind poly(I).poly(C). As measured by thymidine uptake, CBA mice containing a higher percentage of poly(I).poly(C)-binding cells, are high responder mice to poly(I).poly(C), compared with low responder BALB/c mice.


Failure of medial forebrain bundle or raphe ablation to alter the daily temperature rhythm of the rat. The data presented in the present study suggest that neither the ascending noradrenergic fibres confined to the MFB nor the serotonergic fibres originating in or passing through the mesencephalic raphe are essential for periodicity in body temperature. Both control and experimental groups, i.e., rats subjected to medial forebrain bundle or raphe ablation presented circadian periodicity in body temperature and neither the phase, amplitude or overall mean of experimentals differed significantly from controls.


The fine structure of growing and non-growing whole glia cell preparations. Human glia cells become blocked in G1 if starved of serum. The characteristics of the GI blocked state are flattening on the substrate, and absence of cell translocation, ruffling and macropinocytosis. Re-entry into the cell cycle, as a result of growth factor stimulation, is accompained and even preceded by the return of this cellular locomotion. We have studied the fine structure of intact human glia cells and ultrathin sections of these cells when proliferating normally in vitro, when starved of serum and during their return to the cell cycle following stimulation with mEGF (mouse epidermal growth factor). Particular attention was paid to morphologically definable components of the cellular musculoskeletal system. Proliferating interphase glia generally had a leading lamella containing few organelles and oriented bundles of 7 nm microfilaments with structureless lamellipodia at their tips, which often formed ruffles. The perinuclear area was thick and contained many cell organelles, including mitochondria and secondary lysosomes. Glia starved of serum were thinly spread; their peripheral cytoplasm was filled with a diffuse mat of microfilaments, they had no structureless lamellipodia and their perinuclear areas, although thinner, contained cell organelles in equal amounts and of similar type of those found in proliferating cells. On EGF stimulation, after approximately 2 hours the perinuclear area of the cells thickened, and structureless lamellipodia subsequently appeared at the tips of the leading lamellae, forming ruffles. The cells finally began to translocate, the process being accompained by the reorientation and packing of the microfilaments into bundles. As the kinetics of EGF binding and break down by glia cells are similar to those described for fibroblasts, the findings do not support the concept of EGF receptor interactions inducing ultrastructurally demonstrable microfilament or other musculoskeletal structural changes in the cell. They do, however, define the differing cellular morphologies of motile and immobile structures.


alpha1-Antitrypsin in pancreatic diseases. Lowered, normal or raised alpha1-antitrypsin levels were found in 81 patients with acute or chronic relapsing pancreatitis and pancreatic carcinoma. 51 patients with chronic pancreatitis did not have alpha1-antitrypsin deficiency. Thus, in contrast to other reports, alpha1-antitrypsin deficiency and chronic pancreatitis do not seem to be in common association.


Detection of H2-b and Thy-1.2 surface antigens on the differentiating murine otocyst using Nomarski optics. The 12th postcoital day otocyst appears as a hollow cellular ball of pseudostratified columnar epithelium that has entered into its inital stages of differentiation and organogenesis. H-2b antigen was demonstrated on the ectodermally derived epithelial cells of the otocysts and on the mesodermally derived cells of the surrounding mesenchyme. Thy-1.2 antigen was detected in the mesenchymal cells, but not on the epithelial cells of the otocyst. The use of Nomarski optics as a new method for detecting cell surface staining that would otherwise be undetected by bright field optics was demonstrated.


[The effect of transcutaneous nerve stimulation on labor pain (author's transl)]. The analgesic effect of transcutaneous electric nerve stimulation (TNS) during delivery has been studied. 57 (55.9%) of 102 women treated considered TNS had given them good or very good relief from pain; 24 (23.5%) reported that they had received some relief, while 21 patients (20.6%) were of the opinion that they were not helped by the technique. CTG monitoring ocurred in all cases. No side effects on the fetus or the mother have been noted. A positive aspect of TNS was the quick course of delivery and the absence of obstetrical complications in the cases treated with this method. Therefore the designation of TNS as a new, riskless, but effective technique for pain relief during childbirth seems justified.


[Developments in the diagnosis of colorectal carcinoma. Comparison of various diagnostic groups]. Epidemiological observations on colorectal cancer and the consequences of modern diagnostic methods are reported on patients treated in the Medical and Surgical Hospital of the University of Erlangen during the past 9 years. In this period the distribution of the rectal carcinomas according to the Dukes-classification was constant. Using coloscopy consequently as routine method and by proving occult intestinal bleeding as screening method, we succeeded in diagnosing colorectal carcinomas in an earlier stage of Dukes' classification.


[Improved gastric tolerance of antirheumstic agents by means of concomitant gastrozepin therapy]. A double blind trial is described in which the effect of the specific gastric secretion inhibitor, Gastrozepin, was tested on gastric disturbances during treatment with the antirheumatic drug indometacin. It was shown on further treatment with indometacin and concomitant Gastrozepin therapy that the symptoms could be improved or completely relieved.


Cellular differentiation markers in lymphoproliferative diseases. Immunologic progress has resulted in precise definition of different lymphocyte populations that participate in normal immune responses. It has also led to an understanding of the nature of lymphomas and leukemias as malignant expansions of the various cell types. By using characteristic cell markers, it is now possible to classify many malignancies on the basis of the cell types involved.


Changes in T-cell subsets and their clinical significance in cancer patients. The proportion of T cells that have receptors for IgG-Fc (Fc R+ T cells), the functioning of T cell helpers in immunoglobulin production and the blastogenic response of lymphocytes to PHA and Con A were measured in cancer patients. Increases in the percentage of IgG-Fc R+ T cells were observed in most patients; these were greater in patients with advanced tumours and fell within the normal range after complete surgical removal of the tumour. The functioning of T cell helpers in immunoglobulin production and response of lymphocytes to PHA were poor in those patients in whom IgG-Fc R+ T cell percentages were increased. The lymphocytes of such patients responded well to Con A. These changes in T-cell subsets appear to be related to the presence and progress of tumours.


A histopathological study of lymphoid tissue reaction to metastatic nasopharyngeal carcinoma in nude mice. In attempts to heterotransplant human NPc into nude mice, using seven cultured cell lines, we have succeeded in growing a carcinoma simplex, composed of Epstein-Barr virus-determined nuclear antigen-positive and Epstein-Barr virus genome-positive cancer cells, at the injected site with two of the cell lines. These originated from a spindle-cell carcinoma (Chinese NPC-204) and from a combined-cell carcinoma (Chinese NPC-501), respectively. During the first few passages, wandering macrophages were prevalent and increased in number in response to the presence of the tumours. In conjunction with a gradual decrease in the number of wandering macrophages in the medullary sinuses, diffuse hyperplasia of lymphocytes occurred in regional lymph nodes. As a result of the release of lymphocytes and macrophages into the peripheral lymph nodes, the spleen underwent extensive change, as manifested by the collapse of the splenic cords and the formation of septa studded with granulomas. Under these conditions of immunosuppression, lymphatic metastases were observed during the periods between the 11th and 14th generations and the 24th and 30th generations with NPC-204 and between the 9th and 14th generations with NPC-501. The neighbouring lymph nodes, like the spleen, were often studded with epithelioid-cell granulomas, formed by the aggregation of macrophages around nuclear debris in the subcortical areas. We assume that the clumps of debris are the remnants of metastatic cancer cells which were probably killed by macrophages or by sensitized lymphocytes. If the lymph nodes contain a barrier of granulomas, they are not invaded by tumour cells from the cortical sinuses, except in the rare case of retrograde metastasis from the hilus. It would appear that macrophages can replace T lymphocytes, which are found in very small numbers in the nude mice used in this study, in killing tumour cells and, furthermore, in protecting the lymph nodes from the spread of metastases. Metastasis cannot occur in these nude mice when their lymphoreticular system, especially that of the spleen, is working in a stable balance.


Effects of theophylline, epidermal chalone and x-irradiation on proliferation and differentiation of human keratinocytes in vitro. Outgrowth cultures of normal human epidermis were used to study a possible relationship between growth inhibition and differentiated function. The effects of theophylline, epidermal chalone and x-irradiation on mitoses and the characteristic production of epidermal keratohyaline granules (KG) were examined at various intervals after the treatment. Theophylline (an inhibitor of cyclic nucleotide phosphodiesterase) or epidermal chalone inhibited mitoses and enhanced KG production. X-irradiation inhibited mitoses but had no effect on KG formation. These results indicate that inhibition of proliferation per se is not sufficient to enhance keratinization of human epidermal cells.


The effect of haemorrhage on gastric circulation and acid output in the dog. Blood flow in the portal vein and the left gastric artery was measured electromagnetically and gastric mucosal perfusion was determined by pertechnetate clearance in anaesthetized dogs. Bleeding the animals to arterial pressures of 100 and 60 mmHg respectively reduced portal venous flow and markedly increased the mesenteric inflow resistance. Left gastric arterial and gastric mucosal blood flow were decreased without significant vascular resistance change only in proportion to perfusion pressure reduction. Gastric acid output decreased but did not stop even at the lower level of haemorrhagic hypotension. It is concluded that ischaemia and acid, probably in the presence of regurgitated bile, may play an important role in the development of stress ulcers.


Nature and specificity of effector cells in cell-mediated cytolysis of mouse adenovirus-infected cells. The type of effector cells in immune spleen cells (ISC) responsible for cell-mediated cytolysis of mouse adenovirus-infected cells was characterized. When ISC were pretreated with anti-mouse thymocyte or anti-Thy1.2 serum and complement, their cytolytic activity assayed by the (51)Cr release test was completely abolished, whereas it was not significantly reduced either when ISC were pretreated with anti-mouse immunoglobulin serum and complement or after ISC were kept standing at 37 degrees C for 2 h in a plastic dish to remove adherent cells. These data indicate that the effector cells in ISC are T cells. The release of nonspecific or specific soluble cytotoxic factor(s) from ISC upon contact with mouse adenovirus-infected cells was not demonstrated, but about 30 U of interferon activity per ml was detected. However, 10 times as many units of exogenous interferon or more showed no effect on (51)Cr release from target infected cells or on the inhibition of viral antigen synthesis in infected cells. Experiments with mouse cells of different major histocompatibility antigens indicated that the cytotoxicity of ISC is effective when sensitizer and target cells share all or part of the same H-2 gene complex but not effective when they are of a different H-2 gene complex.


Transfer of immunity against Listeria monocytogenes by T cells purified by a positive selection technique. Affinity columns prepared with rabbit antibody to the F(ab')(2) fragment of rat immunoglobulin were used to separate rat thoracic duct lymphocytes into sub-populations that differ with respect to the density of their surface membrane immunoglobulin. Using this technique, it was shown that lymphocytes in the DNA synthetic (S) phase of the mitotic cycle are added in increased number to the lymph of rats infected with Listeria monocytogenes. The great majority of these S-phase cells lacked a high density of surface immunoglobulin as indicated by their failure to bind to the immunoabsorbent. Cells which can protect recipient rats against a challenge infection with L. monocytogenes also segregated with nonadherent thoracic duct lymphocytes obtained from Listeria-immune donors. These protective cells realized their full immunological potential only in recipients that shared histocompatibility-gene-coded structures with the immune lymphocyte donors. The above findings accord with the view that immunity to L. monocytogenes is mediated in rats by activated T cells which are formed as part of the animal's cell-mediated response to infection. Although Listeria-protective lymphocytes concentrate in the nonadherent, T-cell-enriched fraction, it was consistently observed that the adherent, B-cell-enriched fractions of immune donor thoracic duct lymphocytes also could transfer a low level of antimicrobial resistance. This immunity was restricted in allogeneic recipients, a finding which implies that the protection afforded by the adherent population is related to its content of T cells. Nonadherent S-phase lymphoblasts moved in substantial numbers from the blood into peritoneal inflammatory exudates induced by L. monocytogenes. The above finding encourages the belief that recently activated T cells realize their protective function locally in centers of infection where they have secondary effects on macrophages.


Cellular changes in lungs of mice infected with influenza virus: characterization of the cytotoxic responses. Transpleural lavage of lungs from uninfected C3H mice yielded an average of 300,000 leukocytes per mouse. This number increased eightfold within 6 days after intranasal inoculation with virulent influenza A/Hong Kong/68 (H3N2) virus. Macrophages and lymphocytes in approximately equal numbers comprised 90% or more of the leukocytes both before and during infection. B, T, and null lymphocytes comprised, respectively, 9, 21, and 18% of the leukocytes before infection and 7, 26, and 5% by day 6. In absolute numbers, macrophages and T lymphocytes provided the major increments during infection. Cytotoxic activity of mononuclear cells from lung lavages was compared in a chromium release assay using syngeneic L929 target cells with the activity of mediastinal lymph nodes, spleens, and peripheral blood of uninfected and infected C3H mice. Nonspecific cytotoxicity for target cells infected with H3hkNeq1 or B/Lee influenza virus was found with mononuclear cells from uninfected mice. This activity tended to be highest with lavage leukocytes and was associated with adherent cells, presumably macrophages. Increased virus-specific cytotoxicity was detected with lavage cells by day 6 and persisted through day 9, the period of maximal pneumonia. Similar cytotoxic activity also appeared in cells from the nodes and spleen at this same time but was not detected in peripheral blood cells. The virus-specific cytotoxicity of lavage cells was due largely to a nonadherent cell possessing Fc receptors and theta antigen but lacking C3 receptors; these properties are compatible with actively cytotoxic T lymphocytes. The cytological characteristics of the infiltrating leukocytes and the cytotoxicity data suggest that the local T cell response to influenza virus infection in the lung is a major contributor to the pneumonia observed in this mouse model.


Enzyme-linked immunosorbent assay for detection and quantitation of capsular antigen of Haemophilus influenzae type b. An enzyme-linked immunosorbent assay was developed to detect the presence of the ribose-ribitol phosphate capsular antigen of Haemophilus influenzae type b in laboratory and clinical specimens. The assay is simple, sensitive, specific, and quantitative and should prove to be of value in the diagnosis and management of H. influenzae infections.


Selective binding of blood group-reactive salivary mucins by Streptococcus mutans and other oral organisms. Strains of Streptococcus mutans of four genetic groups and five serotypes, and strains of S. sanguis, S. mitis, S. salivarius, Actinomyces naeslundii, and A. viscosus, were found to bind blood group-reactive (BGR) mucin isolated from whole human saliva. The bacteria studied bound mucins with blood type A or B reactivity to a similar extent, suggesting that the carbohydrate moieties responsible for the A and B antigenic determinants were not involved. The organisms studied appeared to bind different fractions of BGR mucin molecules because preparations absorbed with cells of a given oral species no longer contained BGR molecules which bound to homologous organisms but still possessed BGR components which bound to varying degrees to other bacteria. Differences were even noted among S. mutans strains belonging to different genetic groups and serological types. Immunoglobulins could not be detected in the mucin preparations, and addition of anti-human immunoglobulin A (IgA), IgG, or IgM serum to reaction mixtures did not affect binding. Mucin pretreated with periodate or iodoacetate no longer bound to S. mutans H12 cells, suggesting that carbohydrate moieties and sulfhydryl groups played an essential role. Active cell metabolism was not required for BGR mucin binding; however, pretreatment of H12 cells with periodate or heat (100 degrees C for 15 min) reduced binding. Mucin labeled with [(14)C]phenyl isothiocyanate appeared to bind to S. mutans H12 cells comparably to untreated mucin; the binding also appeared to be specific because less than 15% of the labeled material became bound when incubated with an excess of streptococci. Binding of [(14)C]phenyl isothiocyanate-labeled mucin was not affected by neutral sugars tested or by preparations of c antigen, glycerol teichoic acid, dextran, or crude glucosyltransferase. However, binding was inhibited by several amines. BGR salivary mucins are present in the acquired pellicle covering teeth; the ability of bacteria to selectively bind such components suggest that they may serve as receptor molecules involved in the attachment of bacteria to teeth.


Absence of inhibitory effect of leprosy sera upon normal E rosetting. Inhibitory serum factors in certain infectious diseases (leprosy, tuberculosis, histoplasmosis) and malignant conditions (Hodgkin's disease, primary intracranial neoplasms) are said to be partially responsible for decreased cell-mediated immunity (CMI) and consequent anergy. The immunologic derangement in leprosy is not yet completely understood. In order to determine the effect of sera from patients with leprosy upon the rosetting capacity of normal T. lymphocytes, sera from untreated lepromatous (L) and tuberculoid (T) patients were studied. Control sera were obtained from normal volunteers and from patients with other dermatologic conditions (contact dermatitis and leg ulcer). The data indicated that test sera did not inhibit either spontaneous E rosette formation or active rosetting of normal lymphocytes.


T-lymphocytes and hepatitis B serology.

T-lymphocytes and hepatitis B serology. The incorporation of 14C-thymidine by peripheral blood lymphocytes stimulated by phytohemagglutinin (PHA) and the proportion and absolute number of E-rosettes were determined in 28 prostitutes and the results were correlated with hepatitis B virus (HBV) serology. Women were tested for hepatitis B surface antigen (HBsAg) and its antibody (anti-HBs) as well as for antibody to the hepatitis B core antigen (anti-HBc). It was found that women who were carriers of HBsAg had significantly lower incorporation of 14C-thymidine (median value 14451 counts per minute-cpm) compared to women positive for anti-HBc but negative for the other two markers (median value 28590 cpm) as well as to women negative for all the tested markers (median value 30600 cpm). No significant difference was found among the three groups studied with respect to either the absolute number or the percentage of E-rosettes. The results indicate that the presence of anti-HBc alone, is not related to the responsiveness of lymphocytes to PHA.


Effects of fatigue and recovery on contractile properties of frog muscle. The contractile properties of frog sartorius muscles were evaluated during development of fatigue and recovery. Muscles were stimulated under anaerobic conditions at a rate of 30 stimuli/min. Twitch tension (Pt) decreased 59% and tetanic tension (Po) decreased 52% during 15 min of stimulation. Contraction time and one-half relaxation time increased markedly during the first 6 min and then leveld off. The peak rate of twitch tension development (dP/dt) progressively declined to 33% of its initial value. Maximum shortening velocity did not change significantly. Large increases in Pt and twitch dP/dt occurred during the first 15 s of recovery while Po did not increase significantly in this time. Thereafter, Pt, Po, and, dP/dt all progressively returned towards normal over 30 min. These results show that the initial rapid recovery in Pt is not due to an increase in the capacity to generate force. Po is a better indicator of the force-generating capacity of a muscle because, unlike Pt, it is not affected by changes in the rate of tension development.


Polyene macrolide antibiotic cytotoxicity and membrane permeability alterations. I. Comparative effects of four classes of polyene macrolides on mammalian cells. The relationship between polyene macrolide-induced early membrane damage and cytotoxicity in B1 (hamster), B82 (mouse), and RAG (mouse) cells has been investigated. Filipin (FIL) induced the greatest immediate damage, as monitored by 51Cr release, followed by mediocidin (MED), amphotericin B-deoxycholate (Fungizone) (FZ) and pimaricin (PIM). For long term effect, PIM was the least toxic followed by MED, FZ, and FIL as indicated by 24-hour survival, 72-hour viability, and growth rate of cells. In evaluating polyene macrolide-induced permeability alterations and cytotoxicity two types of interactions with mammalian cells were found: (1) cell toxicity at polyene macrolide levels not eliciting immediate membrane permeability changes; and (2) immediate membrane damage without long range toxicity.


Changes in the values of dental students and dentists over a ten-year period. This paper investigates value changes in dental students and dentists over a ten-year period through a cross-sectional study of all dental students at the University of Minnesota in 1966 and 1976, and a ten-year longitudinal study of a class of dental students who entered in 1967. Findings in both studies showed significant differences in values over the ten-year period, but they could not be attributed to the dental school experience. Findings also showed that the values of the dentists in the longitudinal study changed significantly over the ten years from 1967 to 1977, to resemble those of dental school freshmen in 1976. Comparisons of the two studies indicated that changes in social values and the social pressures of professional role development could have accounted for the findings.


The immune response during aging.

The immune response during aging. Complex studies were carried out on humoral and cell mediated immunity among persons over 60 years of age and persons aged 18-40. Humoral immune responses were not profoundly disturbed in the group of older persons. The level of isoagglutinins was lower in older subjects, but the level of immunoglobulins and antibodies to widespread bacterial and virus antigens (S. typhi O, Kunin's CA, Parainfluenza types I, II and III) was the same in both groups. Cell mediated immunity was more greatly changed. Response to PPD in skin tests, lymphocyte stimulation tests, and the migration inhibition test was reduced in older subjects. Also, in this group, PHA in lymphocyte stimulation tests and the number of E- rosette forming cells was lower than among younger adults. However, responses to other antigens in skin tests, lymphocyte stimulation tests, migration inhibition tests (Candida albicans, SK-SD, Trichophyton) and responses to other stimulants of the lymphocyte stimulation tests (Con A, PWM) were well preserved in older subjects.


Immunochemical investigations on water frog eggs: comparative studies on Rana ridibunda, Rana lessonae and their hybrid Rana esculenta. Eggs of Rana ridibunda, Rana lessonae and their hybrid Rana esculenta were examined for their immunochemical properties. The reaction spectra obtained confirm the hybrid origin of Rana esculenta.


Nile blue fluorescence signals from cut single muscle fibers under voltage or current clamp conditions. A method is presented for recording extrinsic optical signals from segments of single skeletal muscle fibers under current or voltage clamp conditions. Such segments, which are cut from intact fibers, are maintained in a relaxed state, while exhbiting otherwise normal physiological properties, including healthy delayed rectifier currents. Extrinsic fluorescence changes are demonstrated, using the permeant potentiometric probe, Nile Blue A. These changes vary nonlinearly with the controlled surface membrane potential, in a manner which suggests that they arise from potential changes in the sarcoplasmic reticulum. According to this interpretation, a simple model based on the gating charge movement implicated in excitation-contraction coupling, provides a self-consistent description of the voltage dependence of the signal that requires no additional parameters.


Location of the gene for theta antigen in the mouse. II. Three-point crosses place Thy-1 in proximal region of chromosome 9. Males of a partially inbred mouse stock homozygous for cw and d were crossed to AKR/ABom females. Progeny obtained by backcrossing heterozygous F1 females to cw d/cw d males were analyzed for the markers cw, Thy-1, d, and Mod-1. Three- and four-point recombination data are consistent with the map: cw--29--Thy-1--12--d--5--Mod-1, in which cw is nearest to the centromere. These recombination data are discussed in relation to previous multiple-point recombination studies of chromosome 9.


Circadian rhythmicity in the methylation of 5-hydroxyindoles and norepinephrine in the pineal gland of 10 day old rats. In pineals of 10 day old rats 5-hydroxytryptophan, 5-hydroxyindole-3-acetic acid, N-acetylserotonin/5-hydroxytryptophol and norepinephrine are methylated following a circadian rhythm. During the night HIOMT and COMT activities were measured for the above mentioned substrates, while HIOMT activity for 5-hydroxytryptophan and N-acetylserotonin/5-hydroxytryptophol was also determined during daytime.


The Babinski sign and the pyramidal syndrome. The presence or absence of a Babinski sign can be puzzling, but in the light of existing pathological studies it is more fruitful to consider which pyramidal tract fibres release it than whether they release it. This was investigated clinically, by looking for correlations with other reflex changes and with motor deficits in the leg. A survey of 50 patients with a unilateral Babinski sign and six patients who lacked it in spite of other pyramidal tract signs was supplemented with follow-up of the patients who had acute lesions. Appearance of the Bibinski sign proved to depend on the interaction of two factors: (1) activity (not necessarily hyperactivity) in the segmental pathways of the flexion synergy; (2) a motor deficit of the foot, in some cases consisting only in an impairment of rapid foot movements, and probably representing a disturbance of direct pyramidal tract projections to distal motoneurones.


Relation between myelin sheath thickness and axon size in spinal cord white matter of some vertebrate species. The relation between number of myelin lamellae and axon size in the CNS was examined by electron microscopy of spinal cord white matter fibres in different vertebrate species (cat, rabbit, guinea pig, rat, mouse, frog and perch). The results show that the number of myelin lamellae increases with increasing axon size in a non-linear fashion. Below an axon size of 4--5 micron the relation follows a fairly straight line but above this size rectilinearity is lost. The mouse and the frog differ from the pattern shared by the other animals. In the mouse the lamellar number increases more slowly with axon size and the relation is close to linear. In the frog the number of lamellae increases very slowly with axon size and the relation is markedly curvilinear. Measurements of the myelin repeating period show that in the mammals and the frog the average period of thick sheaths is about 85% of that in thin sheaths, in accordance with previous findings in the cat. In the perch a clearcut difference in this respect between thick and thin sheaths is not found. Calculations of the g-ratio on the basis of the findings indicate that it increases with increasing fibre size. This is most pronounced in the perch and the frog in which the g-ratio for the largest fibres far exceeds the functionally optimal value defined in theoretical analyses on impulse propagation.


Glial membrane specializations in extraparanodal regions. Previous freeze-fracture studies of central myelinated nerve fibres have demonstrated a distinctive junction in the paranodal region formed between the terminal loops of the glial cell and the axolemma. This unique junction is characterized by the presence of diagonally oriented rows of particles in the P face and to a lesser extent in the E face of the glial cell and an equivalent pattern in the axolemma. In both, the rows are spaced at 250--300 A intervals. Although this junction was originally thought to be peculiar to the paranodal region, examples of the same pattern have now been seen in extraparanodal regions in the central nervous system where they appear as circumscribed patches of membrane exhibiting a pattern identical to that in the paranodal glial loops. All examples found were in the immediate vicinity of myelinated nerve fibres and in one case the membrane containing the specialized patch was identified as a lamella of a myelin sheath. These observations constitute evidence that this distinctive membrane specialization is not limited to the paranodal axoglial junction but can also be found in glial membrane specialization is not limited to the paranodal axoglial junction but can also be found in glial membranes not in immediate contact with the specialized membrane of the paranodal axolemma.


Cellular accumulation of amines and amino acids in the central ganglia of a gastropod mollusc, Planorbis corneus: an autoradiographic study. The distribution of radioactivity was examined autoradiographically in ganglia exposed to 10 different tritium-labelled compounds, some putative transmitters and the others transmitter precursors. The autoradiographic pattern was found to vary greatly for different substances, suggesting the presence of several different accumulating systems in the ganglia. Identified amine-containing neurons take up their own transmitter substance specifically. However, whereas uptake by dopamine-containing, and presumed histamine-containing neurons occurs over both perikarya and processes, in 5-HT-containing neurons it appears restricted to axon processes. The transmitter precursors L-DOPA and 5-hydroxytryptophan were taken up by the perikarya of both dopamine- and 5-HT-containing neurons, possibly by the same uptake system. In high concentrations, tyramine was selectively accumulated by cells containing dopamine and by non-dopamine (possibly octopamine- or tyramine-containing) neurons, but in low concentrations it labelled only the latter. GABA labelled a separate population of neurons and was particularly concentrated in their processes. Some, if not all, of the neurons specifically labelled after exposure to glutamic acid are neurosecretory cells. Tyrosine and glycine appeared to be accumulated in a non-specific manner and many of the substances were also accumulated by glial cells or by parts of the connective tissue capsule.


Isolated fourth ventricle as a complication of ventricular shunting. Report of three cases. Signs of cerebellar dysfunction combined with signs suggestive of shunt malfunction developed in three children with obstructive hydrocephalus. Shunt function was normal. In all cases, the cerebellar signs persisted and computerized tomography scans revealed enlargement of the fourth ventricle. Shunting of the fourth ventricle returned the patients to normal function.


Isolated histiocytosis X of the hypothalamus. Case report. Failure to consider histiocytosis X in the differential diagnosis of hypothalamic masses may lead to inappropriate empirical radiotherapy. This report concerns a case of histiocytosis X of the hypothalamus, unassociated with systemic histiocytic lesions, in which early biopsy allowed specific therapy with subsequent total regression of the lesion.


Splenoportography in the pediatric age group. Eleven splenoportograms were performed in 10 patients between the ages of 2.5 and 17 yr. A definitive diagnosis was made in every instance. There were no complications despite the fact that 6 patients had platelet counts less than 100,000/mm3. Fear of potential complications is unwarranted, and splenoportography should be an essential part of the workup of a child suspected of having portal hypertension. Splenoportography, when combined with measurement of splenic pulp pressure, provides precise information regarding the presence of and/or change in portal hypertension and its underlying cause. With this information, therapy for the pediatric patient with portal hypertension can be individualized and managed in a logical fashion.