Effects of specific inhibitors of 5-hydroxytryptamine uptake on thermoregulation in rats. 1. The effects of two inhibitors of uptake pump in serotonergic neurons, Lilly 110140 and chlorimipramine, on the thermoregulatory responses of unanaesthetized rats to different ambient temperatures (Ta) of 8, 22 and 30 degrees C were assessed. 2. Intraperitoneal administration of either Lilly 110140 or chlorimipramine produced dose-dependent hypothermia at 8 and 22 degrees C Ta. At 8 degrees C Ta the hypothermia was due to a decrease in metabolic heat production. At 22 degrees C Ta, the hypothermia was brought about by both a decrease in metabolic heat production and an increase in cutaneous temperature of the tail and the footsole. 3. However, at 30 degrees C Ta, there were no changes in rectal temperature in response to either Lilly 110140 or chlorimipramine application. 4. The data suggest that an increase in serotonergic receptor activity or in functional serotonin in brain decreases heat production and/or increases heat loss and leads to hypothermia in rats.


Mode of action of levamisole.

Mode of action of levamisole. Levamisole is a heterocyclic compound that is an effective antihelminthic agent and is also immunoregulatory. Its likely immuno-regulatory mode of action is by mimicry of the thymic hormone thymopoietin. Chemically, levamisole may form a thymopoietin-mimetic tertiary structure, stimulate lymphocytes by its imidazole component, or be metabolized to O.M.P.I., a reducing compound which affects radical scavenging in multiplying lymphocytes. Physiologically, thymopoietin affects many components of the immune system including both neutrophils, macrophages, and lymphocytes and its therapeutically important actions are probably targeted at stimulation of phagocytosis and stimulation of regulatory T cells to restore homeostasis in a perturbed immune system.


Power density spectra of frog skin potential, current and admittance functions during patch clamp. Clamp current fluctuations in frog skin of areas down to 0.07 cm2 are dominated by low frequency components (less than 100 Hz). Patch clamp of 0.001 cm2 under high density fluorosilicone oil exhibits components up to 5000 Hz, often including a peak in the current power density spectrum. The admittance spectrum also exhibits a peak at the same frequency. In some skins no peak was observed, but the break in the curve was too sharp to be Lorentzian. In all instances the final limiting slope approached 1/f2. The resonance peak was observed in either Cl- or SO = 4 Ringer's but disappeared when Na+ was replaced with K+. Resonance frequency varied from 100 to 700 Hz.


Effect of amiloride on catecholamine-induced changes in ion transport in short-circuited frog skin. The effect of amiloride (10(-6) M), added either before or after the catecholamine, on the adrenaline- or isoprenaline-induced changes in short-circuit current and Na and Cl fluxes of isolated skin of Rana temporaria was investigated. At the catecholamine concentration used the increment in short-circuit was the same in the absence or presence of amiloride (ca. 7.1 neq.cm-2.min-1) and the amiloride inhibition was the same in the absence or presence of catecholamine (ca. 9.4 neq.cm-2.min-1). Amiloride inhibited the Na and Cl influxes of the control period (by --8.63 +/- 1.28 and --2.08 +/- 0.75 neq.cm-2.min-1, respectively) but did not prevent the increase of these fluxes on the addition of adrenaline. There was no evidence of amiloride inhibition of the Na and Cl effluxes. There was an association between the increase of Na efflux and net Cl efflux following adrenaline, which if secreted together by a neutral NaCl pump would not contribute to the increased short-circuit current. The increased short-circuit current was correlated with the increased Na influx throughout the experiment if allowance is made for the periods where there is a lag between the current and isotopic measurement (i.e., the period immediately after the addition of a drug). It is tentatively suggested that the catecholamine-induced increase in Na influx is not altered by the amiloride concentration used in this study. In addition the magnitude of the changes induced by catecholamine in the influx and efflux of both Na and Cl seem to be unaffected.


Interdependence of the two borders in a sodium transporting epithelium. Possible regulation by the transport pool. Specific binding of 14C-amiloride to the mucosal surface of frog skin epithelium (Rana temporaria) has been used as a measure of the number of sodium entry sites. All binding measurements were made with the mucosal surface bathed in a solution containing 1.1 mM sodium. When manipulations were used which increased the intracellular concentration of sodium the amount of amiloride bound was reduced. The manipulations included flushing the mucosal surface with solutions containing 111 mM sodium after serosal efflux was inhibited with ouabain or potassium removal. Similar results were obtained when cells were loaded with lithium. These effects on amiloride binding did not appear to depend on changes in membrane potential or upon changes in affinity of amiloride for its binding site. It appears that inhibition of serosal sodium efflux from the epithelium causes a reduction of mucosal sodium influx by making entry sites unavailable. This latter may be a result, directly or indirectly, of the sodium concentration in the sodium transport pool.


Nonhormonal mechanisms for the regulation of transepithelial sodium transport: the roles of surface potential and cell calcium. An attempt to define the main categories of regulatory mechanisms of transepithelial sodium transport across tight epithelia is presented. In particular, evidence suggesting two types of mechanisms, changes in surface potential and the level of cell Ca, are described in greater detail. We have measured the effects of conditions that affect surface potential on the transepithelial sodium transport. Those conditions that increase the screening of negative charge and therefore depolarize the outer membrane are expected to have effects homologous to a depolarization caused by external current. Indeed, when the composition of the outside solution was modified by (i) increasing ionic strength, (ii) adding polyvalent cations (La+++, Co++, Ni++, Cd++), or (iii) lowering pH, an increase in active Na transport was detected. Moreover, the presence of small concentrations of polyvalent cations which screen surface charge, markedly dampens or even eliminates the effects of pH or ionic strength on Na transport. These findings provide additional support for the notion that a potential-sensitive component regulates Na movements across the apical membrane of the frog skin, and offer a framework to understand the effects of numerous cationic agents on transepithelial transport that hitherto remain unexplained. With respect to the role of intracellular Ca we have found that procedures that increase cell Ca, like removal of sodium in the basal solution or addition of ionophore A23187, reduce transepithelial Na transport. Moreover, conditions that block the increase in cell Ca prevent the inhibition of transport. These observations suggest that the level of intracellular Ca may determine the rate of transepithelial Na transport.


Morphological aspects of some sodium transporting epithelia suggesting a transcellular pathway via elements of endoplasmic reticulum. Electron microscopic studies of sodium transporting epithelia from frog skin, sheep choroid plexus, rabbit gallbladder and small intestine, and rat kidney revealed the presence of a complex intracellular system of tubulo-cisternal endoplasmic reticulum which appeared to connect apical (luminal) and baso-lateral cell surfaces. The system was present in the tight epithelium of frog skin but was most abundant in leaky epithelia with low transepithelial resistance and isotonic transport. The basic structural features of the system and its relationship with some associated components are described. Our result, coupled with preliminary physiological studies, indicate that developmental and seasonal (hormone-induced) changes in the configuration of the tubulo-cisternal endoplasmic reticulum may be closely correlated with specific changes in epithelial permeability. The findings are discussed in the light of the hypothesis that epithelia possess two sodium transporting systems: One based on pump sites in the plasma membrane producing a hypertonic transportate and another located in the membranes of the tubulo-cisternal endoplasmic reticulum which, due to its extensive surface, would be well suited for producing an isotonic transportate.


Fine structure of the secretory and non-secretory ameloblasts in the frog. II. Fine structure of the non-secretory ameloblast. The non-secretory ameloblasts present at the enamel-free surfaces of maxillary teeth in the frog Rana pipiens were examined by electron microscopy at different stages of tooth development. Their main fine structural features seem to reflect a transport function. During early tooth development, the non-secretory ameloblasts adjacent to odontoblasts and predentin exhibit extensive lateral surface specializations and numerous cytoplasmic vesicles. During late tooth development, the non-secretory ameloblasts adjacent to mineralizing dentin show numerous cellular junctions, well-developed intercellular channels with numerous interdigitating processes and labyrinthine configurations at their distal surfaces. An intact basal lamina is present between the non-secretory ameloblasts and the dentin surface until the dentin becomes fully mineralized. At this stage the adjacent cells no longer exhibit surface specializations. It is suggested that the non-secretory ameloblasts may participate in the mineralization of adjacent dentin at the enamel-free surfaces. This surface dentin becomes fully mineralized at a later stage of development than the underlying dentin.


Galvanic disruption of vestibulospinal postural control by cochlear implant devices. All subjects with implanted cochlear stimulators demonstrated evidence of abnormal postural stability without their stimulators activated. Instability increased when they were tested with cochlear stimulation units turned on, and additional instability was demonstrated in four of these subjects when tested in noise. These findings suggest that the electrical stimulation delivered by the cochlear prosthesis is not limited to the auditory system. The precise characteristics of electrical stimulation devices designed for stimulations limited to the cochlea and their spurious effects upon motor performance should be investigated. The design of future intralabyrinthine auditory electrical prostheses must include hardware designs and stimulus paradigms that avoid undesirable vestibular system stimulation.


Host range restriction of vaccinia virus in Chinese hamster ovary cells: relationship to shutoff of protein synthesis. Chinese hamster ovary cells were found to be nonpermissive for vaccinia virus. Although early virus-induced events occurred in these cells (RNA and polypeptide synthesis), subsequent events appeared to be prevented by a very rapid and nonselective shutoff of protein synthesis. Within less than 2 h after infection, both host and viral protein syntheses were arrested. At low multiplicities of infection, inhibition of RNA synthesis with cordycepin resulted in failure of the virus to block protein synthesis. Moreover, infection of the cells in the presence of cycloheximide prevented the immediate onset of shutoff after reversal of cycloheximide. Inactivation of virus particles by UV irradiation also impaired the capacity of the virus to inhibit protein synthesis. These results suggested that an early vaccinia virus-coded product was implicated in the shutoff of protein synthesis. Either the nonpermissive Chinese hamster ovary cells were more sensitive to this inhibition than permissive cells, or a regulatory control of the vaccinia shutoff function was defective.


T lymphocytes inhibiting factors in renal cancer: evaluation of differences between arterial and renal venous blood levels of E rosette forming cells. The cellular immune response has been reported to be impaired in patients with renal cancer and to be increased by removal of the tumor bulk. T lymphocyte levels in the vein of the neoplastic kidney were investigated in 4 patients to assess the presence of a T lymphocyte inhibiting factor produced by the tumor. T lymphocyte levels resulted in significantly decreased tumorous venous blood, whether compared to arterial, contralateral or peripheral blood. A similar result was not found in 10 control patients. Some hypotheses on the nature of this T lymphocyte inhibition are discussed.


Electrical stimulation for incontinence in myelomeningocele. Urinary incontinence is the most obvious urinary tract complication in children with myelomeningocele. Incontinence is owing to a hyperreflexic (spastic) bladder and/or pelvic floor weakness, which responds to functional electrical stimulation. Of 33 incontinent children the criteria for functional electrical stimulation were absent in 21 because of denervation of the pelvic floor muscles. Of 6 children who used functional electrical stimulation 5 had a successful result. However, incontinence recurred in 3 of the 5 patients between 6 and 18 months after functional electrical stimulation treatment was completed and they are awaiting repeat treatment.


Electrical stimulation for voiding dysfunction after spinal cord injury. Incontinence and frequency of voiding were present after spinal cord injuries in 18 patients. A hyperreflexic bladder and/or pelvic floor weakness was found in these patients. Functional electrical stimulation resulted in relief or improvement of symptoms in 9 of the 11 patients in whom this procedure was used. An increase in anal sphincter pressure with functional electrical stimulation was a more reliable criterion than an increase in maximum urethral pressure in the selection of patients for the procedure.


[State of the distal bed of the cardiac coronary arteries in ischemic heart disease]. The condition of the distal bed of the cardiac coronary arteries was studied in 150 patients with ischemic heart disease. It proved to be affected with stenotic atherosclerosis in 20,6% of cases. The distal bed in patients with the chronic stage of ischemic heart disease hardly differed from that in patients with acute myocardial infarction. Total revascularization may be accomplished in 33% of cases with affection of three vessels of the cardiac coronary bed with stenotic atherosclerosis and in 96,5% of cases with affection of one vessel.


[Field of vision established by perimetry in achromatopsia (author's transl)]. The results of perimetry especially of profile perimetry is in cases of achromatopsia so typical and unmistakable that it can be referred to for the differentia.  l diagnosis of this disease. This follows from an examination of 33 cases with congenital achromatopsia. In all cases profile perimetry was flattened in the fixation area but not nearly as strong as it is usually the case if visual acuity is decreased to 0,1. 7 times there was found a small central scotoma at the margin of which it is fixated. The reason for the diverging of light difference sensitivity and visual acuity is discussed.


[The significance of fluorescein angiogarphy in ocular toxocara granuloma (author's transl)]. Four serologically-proved cases of intraocular toxocara infections are demonstrated. Three different manifestations in the following way were found: 1. Solitary granuloma on the posterior pole (2 patients). 2. Anterior and posterior uveitis of both eyes with granuloma near the ora (1 patient). 3. Iridocyclitis of both eyes (1 patient). The fluorescein angiography examination in two cases with solitary granuloma have been repeated over a period of time and the relation of the satisfactory results to the further development of the disease is shown.


[Penetration of gentamycin into the aqueous humor of non-inflamed and inflamed human eyes (author's transl)]. The penetration of gentamycin into aqueous humor after parenteral application (i. m., i. v., s. c.) of non-inflamed and inflamed human eyes was investigated. The dose of gentamycin was 80 mg i.m. and i. v. respectively. A doses of 40 mg gentamycin was used by s. c. injection. With Agar-diffusions test it could be demonstrated that the level of gentamycin was higher in inflamed than in non-inflamed eyes.


[Concentration of minocycline in human aqueous humor after oral administration (author's transl)]. For antibacterial prophylaxis in intraocular surgery minocycline was administered in oral dosage in 22 cataract-patients. The concentration levels reached in the aqueous humor were determined. The detected levels ranged in some cases from 0.08 to 0.2 mcg/ml, the majority was below 0.06 mcg/ml.


[Results of Nandrolone therapy (Keratyl) in lesions and diseases of the cornea (author's transl)]. The authors report on clinical experiences with the topical application of the synthetic hormone Nandrolon (Keratyl) in diseases of the cornea caused by exogenic, neurogenic, and combined exogenic-endogenic factors. In all cases a positive regenerative effect on epithelium and stroma of the cornea seemed to exist. The present results seem to allow the following range of indications: 1. injuries of the epithelial tissue; 2. ulcera of the cornea (combined with antibiotics); 3. dystrophic diseases of the cornea; 4. certain postoperative treatment after keratoplastic surgery.


[Loss of inhibitors of the blood coagulation system in protein-losing enteropathy (author's transl)]. The investigation of the haemostasis of a 11 6/12 years old boy with protein-losing enteropathy revealed signs of hypercoagulability of the coagulation system, due to a decreased plasma concentration of antithrombin III and alpha1-antitrypsin, that were lost with other proteins in great amounts into the intestinal tract. The loss of these two important inhibitors of the coagulation system can lead to thrombotic complications in patients with protein losing enteropathy.


Antibasement membrane disease. II. Mechanism of glomerular injury in an accelerated model of Masugi nephritis. Rabbits were given injections of preformed complexes of purified goat antirabbit glomerular basement membrane antibody and rabbit antigoat immunoglobulin. When the animals were killed 24 hours later, examination of their kidneys revealed diffuse glomerulonephritis with widespread areas of localized loop necrosis, associated with extensive accumulations of polymorphonuclear leukocytes. By electron microscopy, accumulations of polymorphonuclear leukocytes in various degrees of disintegration were associated with areas of the basement membrane that appeared to be losing their structural integrity, suggesting that the damage to the membrane was brought about by the action of lysosomal enzymes. Reduction of the number of circulating polymorphonuclear leukocytes by pretreatment of the animals with nitrogen mustard completely prevented the lesions. Reduction of circulating complement levels by pretreatment of the animals with cobra venom factor prevented the occurrence of localized necrosis but allowed the development of the diffuse lesion.


Mitogenic response to epidermal growth factor: relationship to number, affinity, and down-regulation of EGF receptors in three murine embryo cell lines. Swiss 3T3 and C3H-M2 cells have a greater mitogenic response to epidermal growth factor (EGF) than do C3H10T 1/2 cells. The latter cell line, however, has a number of EGF receptors per cell intermediate between the two cell lines that have a more vigorous response to EGF. Scatchard analysis of binding data indicate that all three cell lines have one class of EGF receptor, with indistinguishable affinity for the ligand. When exposed to 10-nM EGF all three cell lines "down-regulate" their EGF receptors with the same time course, and to the same percentage of initial receptors.


Iowa results of acoustic neuroma operations. The records of 10 patients, who underwent removal of small vestibular schwannomas by the middle cranial fossa approach at the University of Iowa Department of Otolaryngology and Maxillofacial Surgery between October 1974 and November 1977, are reviewed. The principal deviation from previously described operative techniques is that after identification of appropriate landmarks, the internal auditory canal is first unroofed in its medial portion near the porus rather than following the facial nerve to the fundus of the canal. There were no intraoperative complications, but one patient died after a postoperative brain stem vascular accident. Another patient developed a cerebrospinal fluid leak and, subsequently, meningitis. Auditory function was preserved postoperatively in 8 of 10 patients, but only 6 retained auditory function after discharge from the hospital. Facial nerve function was normal immediately after surgery in 6 of the 10 patients, but return was incomplete in 2 patients more than 1 year after surgery. Postoperative routine and special audiometric studies are discussed.


Stapedectomy--in depth analysis of 2405 cases. An optical reader system used in conjunction with a CDC 6400 computer was utilized to obtain data summaries related to the stapedectomy procedure. Medical and audiological data of 2405 cases undergoing surgery for otosclerosis were analyzed. Results are reported in tabular, figurative and descriptive forms.


Increased von Willebrand factor in diabetes mellitus. Abnormal platelet function may play a role in the genesis of vascular complications in diabetes mellitus. We measured plasma levels of ristocetin-Willebrand factor and factor VIII antigen in 75 subjects and also measured aggregation-enhancing factor in subsets. We found increased levels of ristocetin-Willebrand factor in all groups of diabetics studied, even in mild diabetics free of vascular disease. Factor VIII antigen was increased only in diabetics with vascular disease. We could not find an aggregation-enhancing factor in any group.


Medical students, medical records and clinical skills. 140 Liverpool medical undergraduates from all three clinical years completed a two part questionnaire. The first part gave their opinion on the contents of medical case records and how they personally recorded and used them. The second part showed the usefulness to students of their teachers' assessments of their clinical skills. The results indicated that the present case record and assessment of clinical skills were unhelpful in the students' education. The type of record-keeping which students thought best was very similar to the problem-orientated medical record (POMR). The kind of assessment of clinical skills which they would like was very similar to the educational audit linked with POMR. In view of these findings, the introduction of POMR into the undergraduate curriculum is strongly advocated.


Treatment of demyelinating and degenerative diseases by electro stimulation of the spinal cord. Electrical stimulation was applied to the spinal cord of 75 patients who had demyelinating and degenerative diseases of the central nervous system, and 3 patients who had sustained spinal cord injuries. The electrical energy was delivered to the central nervous system by the percutaneous technique. The amount of electrical energy required to produce the perception of paresthesias was measured in 11 patients. The minimum power necessary was 76.89 muW, the maximum was 868 muW, and the average was 448.8 muW. The patients were evaluated by 4 examiners by means of routine neurologic examination, videotape movies, and measurement of urinary bladder function. Continued improvement in neurological status, which allowed the patient to live a better lifestyle, occurred in 30 of the 61 patients with multiple sclerosis, and 6 of the 10 patients with ataxia. The patient with transverse Myelitis, the patient with primary lateral sclerosis, and 1 patient with olivopontocerebellar atrophy; also noted similar enhancement of neurological function. The patients with amyotrophic lateral sclerosis and spinal cord injuries had no changes of significance. Thirty-two out of 44 patients who were ambulatory had significant improvement, whereas 10 of the 19 patients who were not ambulatory had improvement. There was no evidence that electrical stimulation of the spinal cord, when applied via dorsally placed percutaneous electrodes and when carried only to the perception of a paresthesias, has any adverse effect on neurological function. It is hypothecated that the electrical current alters neurotransmitters to enhance the transmission along nervous and neurochemical pathways. The exact mechanisms are unknown at the present time.


The role of pre-replication and post-replication processes in mutation induction in Haemophilus influenzae by N-methyl-N'-nitro-N-nitrosoguanidine. Studies were carried out on the repair and fixation of premutational damage induced in Haemophilus influenzae by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). The studies employed a temperature-sensitive DNA elongation mutant (dna9) and its combinations with mutants defective in pyrimidine dimer excision (uvr1, uvr2) and in recombination (rec1). The dna9 mutant is shown to be leaky, allowing about 1% of the normal rate of DNA synthesis at the restrictive temperature. Repair of premutational lesions was detected by a decline in mutation frequency with increasing delay in DNA replication in dna9 at the restrictive temperature. This repair is unaffected by the pyrimidine dimer excision system. Mutation fixation was detected by the ability of DNA from treated and then lysed cells to transfer mutants to recipient cells by transformation. Some fixation occurred at the restrictive temperature but much less than at the non-restrictive temperature suggesting that an appreciable minority of the mutations resulted from lesions introduced near the replication fork but that the majority of mutations arise from lesions introduced at some distance from the fork, perhaps randomly. The DNA synthesized immediately after MNNG treatment is of lower molecular weight than normal and returns to normal with time. This return is blocked in the rec1 mutant, suggesting that recombination is involved. The possible role of this process in MNNG mutagenesis is discussed.


Coronary bypass for stable angina: a prospective randomized study. To evaluate the effects of coronary-artery bypass, 100 patients with stable, disabling angina were randomized to medical (49) or surgical (51) therapy. There was no statistical difference in major cardiac events after three years (death in five medical vs. four surgical, infarction in eight vs. 10, and unstable angina requiring operation or reoperation in eight vs. three cases). Surgical patients with three-vessel disease had fewer major events (P less than 0.05) than the comparable medical group and less unstable angina requiring operation (P less than 0.02). All unstable angina was less frequent in the surgical group (15 vs. six, P less than 0.01). Functional classification improved more in surgical patients at six months (P less than 0.01) and at late followup examination (P less than 0.05). After six months, surgical patients achieved significantly higher exercise work loads (P less than 0.01), exercise heart rates (P less than 0.05), maximum paced heart rates (P less than 0.01) and myocardial lactate extraction (P less than 0.01). On the basis of this interim report of a relatively small group of patients, we conclude that bypass results in greater functional improvement and less unstable angina than medical therapy. The likelihood of death and myocardial infarction is unchanged by operation.


Evidence for defective immunoregulation in the syndrome of familial candidiasis endocrinopathy. We studied three children with candidiasis endocrinopathy syndrome, together with their parents and five siblings, to explore the possibility that defective immunoregulation allows autoimmune phenomena to be involved in the pathogenesis of this syndrome. Inheritance of the syndrome appeared to be autosomal recessive. Immunologic abnormalities in this family included hypergammaglobulinemia, selective IgA deficiency, anergy, autoimmune endocrinopathies and active chronic hepatitis. Defective suppressor T-cell function was noted in the two surviving children with clinically apparent disease and in a clinically normal sibling. Analysis of the immunologic abnormalities in the family suggests that defective immunoregulation rather than disordered effector mechanisms may explain the large number of immunologic defects noted. These defects, in turn, may result in the clinical manifestation of the syndrome.


In vivo and in vitro effects of thymosin and adenosine deaminase on adenosine-deaminase-deficient lymphocytes. Two siblings with adenosine deaminase deficiency were studied before and during "enzyme replacement" therapy (partial exchange transfusions with normal red cells containing the missing enzyme). The younger sib showed improvement of immunologic function during red-cell therapy alone, whereas in the older sib this improvement occurred only when the transfusions were supplemented by thymosin injections. Their clinical courses correlated with in vitro findings: lymphocytes from the younger sib differentiated to T-cell-rosette-forming cells upon addition of adenosine deaminase alone; lymphocytes from the older sibling required supplemental thymosin to form these cells. Thymic factors appear to influence the response to transfusion therapy in some patients deficient in adenosine deaminase, and supplementation of red-cell transfusion with thymic factors may be required.


The action of caffeine in promoting ultrastructural damage in frog skeletal muscle fibres. Evidence for the involvement of the calcium-induced release of calcium from the sarcoplasmic reticulum. 1. Caffeine at concentrations above 5 mM was shown to cause rapidly extensive ultrastructural damage to the myofibrils of frog skeletal muscle. 2. The effect was promoted at lower temperatures, whereas the myofibrils were protected by prior exposure to procaine. 3. It is argued that caffeine causes a Ca2+-induced release of Ca2+ (the CROC) from the S.R. and that the consequent rise in [Ca2+]i promotes the ultrastructural damage observed. 4. Myofibril digradation is also produced by treatment of the muscle with the divalent cation ionophore A23187; this effect is not protected by either procaine or Dantrolene sodium. 5. It is suggested that A23187 causes the release of Ca2+ from the S.R. by a mechanism that differs from both excitation and the CROC; the resultant rise in [Ca2+]i again causes myofibril degradation. 6. The ways in which a marked rise in [Ca2+]i could cause muscle damage and the possible relevance of these findings to the sequence of events in the development of myopathies of human skeletal muscle are discussed.


Thymic and peripheral blood T- and B-cell levels in myasthenia gravis. We have compared the percentage of T and B lymphocytes in the thymus and peripheral blood populations of patients with myasthenia gravis. There were significantly fewer thymic T cells in myasthenic hyperplastic thymus (MG-H), but not in myasthenia gravis-thymoma (MG-T), compared with normal thymus biopsies obtained at cardiac surgery. Conversely, B cells were increased in MG-H versus MG-T and normals. Peripheral blood T and B cells were not different in any group of myasthenic patients compared to normal populations. In vitro autologous mixed lymphocyte reactions between thymus and peripheral blood lymphocytes occurred in MG-H, but did not correlate with the degree of thymic B-cell increases in these patients.


[Role of platelet serotonin in hyperperistalsis after digestive hemorrhages]. Intestinal transit accelerates during gastroduodenal haemorrhage. To test a personal theory that the reason is to be found in serotonin released by platelets and absorbed by the intestine, the behaviour of serotoninaemia has been studied. This proved to be 1.35-9.7 microgram/l (mean: 4.175 microgram/l; E.S. +/- 1.39) in patients with haematemesis and melena, compared to 0.49-0.9 microgram/l (mean: 0.728 microgram/l; E.S. +/- 0.07) in the controls (p less than 0.001). The increase in circulating serotonin to significant values is probably due to hormone release. This dose not occur in cases of melena alone, probably owing to the organism's high capacity for catabolism.


[Activity of proteases, leucine arylamidase and alpha-amylase in pancreatic tissue during nickel deficiency]. In studies on the essentiality of nickel, important differences of enzyme activities and also of substrates were established. The results of the present paper show that these changes cannot be explained by a lowered reduction of dietary proteins, since the activity of the proteases rather increased during Ni deficiency. However, the digestion of the starch by alpha-amylase, being 57% lower, could have been partially responsible for the large differences in the activities of the hepatic enzymes and in the concentrations of the hepatic metabolites and also in the weight gains.


The influence of chronic cerebellar stimulation on respiratory muscle coordination in a patient with cerebral palsy. The effect of chronic cerebellar stimulation on respiratory muscle coordination has been evaluated using a relatively simple and objective target breathing test on one patient. Seven normal subjects were used as controls. Magnetometer recordings were used to determine whether abdominal and rib cage expansion were in phase. Subjects were asked to match their breathing frequency to a metronome signal. Their ability to control respiratory timing voluntarily was assessed in terms of the coefficient of variation (CV) of inspiratory time (Ti) and of expiratory time (Te). The CV's of Ti and Te were much greater in the patient in the absence of cerebrellar stimulation than they were in normal subjects. Both at 3 weeks and 6 months after implantation of the stimulator, a significant improvement in the performance of the patient was demonstrable with the stimulator on, although normal values were never achieved. This demonstrable influence of chronic cerebellar stimulation on respiratory muscle coordination has important implications for both the avoidance of respiratory complications and the potential improvement of speech in patients with cerebral palsy.


Active pharmacologic management of the third stage of labor. A comparison of oxytocin and ergometrine. Postpartum hemorrhage is a common and serious complication of the third stage of labor resulting in anemia and increased morbidity in the puerperium. Administration of uterotonic drugs and suitable mechanical assistance in delivery of the placenta may significantly reduce this hazard. Ergometrine and oxytocin have been used for a long time in markedly different doses and by various routes of administration with varying success. In order to compare these two oxytocics with regard to their hemostatic effects as well as their possible interference with the physiologic placental separation mechanism, three groups (ergometrine, oxytocin, and control) of women have been studied during a 2-year period. Ergometrine (0.2 mg) and oxytocin (10 IU) administered in the stated doses and as single intravenous injections are comparable with regard to hemostatic efficiency, but oxytocin seems to promote placental separation and expulsion better and thereby reduces the risk of partial retention and trapping with bleeding reguiring further emergency measures as a frequent consequence.


Allergies of the dental pulp.

Allergies of the dental pulp. A review of publications relating to the allergies of the dental pulp is presented. The pulp--especially when inflamed--contains antigens, lymphocytes, plasmocytes, IgG, IgM, IgA, and IgE antibodies, mast cells, histamine, and possibly C3. However, no antibody-mediated allergy (hypersensitivity) of the pulp has yet been demonstrated. On the other hand, two types of cell-mediated allergy--the graft-rejection reaction and contact hypersensitivity--have been reported, as well as autoimmunity.


Electro-ejaculation of a complete paraplegic followed by pregnancy. After having experimented with electro-stimulation on monkeys, the authors have put it into practice with the paraplegic. They report observations on pregnancy of a woman with a complete paraplegic below T4 who was injured 15 years ago. Nineteen electro-stimulations and seven artificial inseminations were necessary. The electro-stimulation is easy and can be repeated at will.


Clinical implications of preseptal (periorbital) cellulitis in childhood. The available hospital records of all pediatric patients diagnosed as having periorbital, preseptal or orbital cellulitis over a five-year period were reviewed and compared to previously reported series. Only two of 39 patients had orbital cellulitis. The 37 patients with preseptal cellulitis had two characteristic clinical presentations. Twenty-two children had local trauma, abscesses, insect bites, or impetigo as the inciting event for their cellulitis. Infection was usually caused by staphylococci or streptococci. In contrast, 15 children, 12 of whom were under 36 months, had associated upper respiratory tract infections and otitis. Haemophilus influenzae was the most commonly implicated pathogen and the children were at risk of bacteremia and metastastic infection. Determination of the location of the infection in the orbit and consideration of the clinical presentation of the patient with infection in and about the orbit are of assistance in choosing appropriate therapy. Young children who have upper respiratory tract symptoms in association with preseptal cellulitis should receive antibiotic coverage for Haemophilus.


Meningitis due to Haemophilus influenzae other than type b: case report and review. A 4-month-old female infant with meningitis caused by Haemophilus influenzae type f had a hospital course complicated by sterile subdural effusions and persistent neurologic abnormalities. One year later she was normal in all respects. The infant's mother had serum bactericidal antibodies to H. influenzae type b but not to type f. During recovery the patient had no bactericidal antibodies to type b, and the type f organism could not be maintained in her serum. Review of the literature identified 40 cases of meningitis reported as caused by H. influenzae other than type b. An evaluation of the ten cases described as due to encapsulated strains (a, e, and f) shows that the age distribution and clinical features are similar to those of meningitis caused by type b. Only five cases of meningitis caused by unencapsulated H. influenzae have been described. Four of the patients were older than the usual age range for type b meningitis and two had prior head trauma. A large clinical trial in Finland with a two-year observation period has demonstrated no untoward increase in non-b H. influenzae meningitis in recipients of a type b vaccine. Serious infections caused by other H. influenzae types will continue to occur sporadically and may increase in frequency when an effective vaccine against type b is widely used in infants.


An outbreak of Pneumocystis carinii pneumonia at a pediatric hospital. Eleven cases of Pneumocystis carinii pneumonia were diagnosed during a 3 1/2-year period at a pediatric hospital where this infection had never been identified previously despite appropriate studies. The incidence of infection was 3.0, 7.4, and 4.2 cases per 1,000 patient months in children being treated for acute leukemia, neuroblastoma, and rhabdomyosarcoma, respectively. The outbreak coincided with increased intensity of chemotherapy for these malignancies. Ten of the patients had received four or more chemotherapeutic agents within three months of the onset of infection. Because no exogenous source of the epidemic was found, latent endogenous infection activated by immunosuppression was presumed to be the ultimate cause of the outbreak. Increased intensity of chemotherapy may result in P carinii outbreaks and may be an indication for anti-Pneumocystis prophylaxis with trimethoprim/sulfamethoxazole in patients at risk.


The current voltage relationship of the delayed outward current in the heart of the frog (Rana esculenta) and the tortoise (Testudo germani). Steady state and non steady state I-V relationships of the resting membrane and delayed rectifying membrane were analysed by applying trapezoid voltage clamp pulses on atrial fibres isolated from the frog and the tortoise. The fibres were disposed in a perfusion chamber for double sucrose gap. In both types of preparation, a component of delayed rectification current was identified which was activated following a comparable time course. The amplitude of the delayed rectification current, when expressed either as normalized to the calculated membrane capacity or to the initial background current, is significantly larger in the frog than in the tortoise. Full activation of the delayed rectifying system can be demonstrated in the tortoise, while in the frog this process is presumably complicated by simultaneous accumulation of K ions in the extracellular region. The difference in magnitude of the delayed outward current has no influence on the duration of action potential which is recorded over the sucrose gap.


Elevating serotonin levels in brain with 5-hydroxytryptophan produces hypothermia in rats. The effect of the 5-hydroxytryptamine (5-HT) precursor 5-hydroxytryptophan (5-HTP) on the thermoregulatory responses of unanesthetized rats were assessed at three different ambient temperatures (Ta) of 8, 22 and 31 degrees C. Intraperitoneal administration of either 5-HTP alone or 5-HTP plus R04-4602 (the peripheral decarboxylase inhibitor) produced dose-dependent hypothermia at both Ta's of 8 and 22 degrees C. The hypothermia was brought about solely by a decrease in metabolic heat production at 8 degrees C Ta. At 22 degrees C Ta, the hypothermia was due to both a decrease in metabolic heat production and an increase in tail and footsole skin temperature. However, at 31 degrees C Ta, there were no changes in rectal temperature in response to either 5-HTP or 5-HTP plus R04-4602 application. The data suggest that an increase in 5-HT levels in brain decreases heat production and/or increase heat loss and leads to hypothermia in rats.


Inward rectification in skeletal muscle: a blocking particle model. Inwardly rectifying potassium currents were measured in resting frog skeletal muscle in different [K]o. A modle is presneted for inward rectification which supposes that the potassium conductance depends on the K+ concentration within a channel and is reduced by a blocking particle which is driven into the channel by depolarization.


[Polar acid phosphatase as T lymphoma marker (author's transl)]. The comparative morphological and histochemical studies of human thymic lymphocytes and 2 T--cell lymphomas allow the authors to emphasize the diagnostic value of a polar cytoplasmic acid phosphatase activity. This simple cytochemical method can provide permanent documentation easily stored and counted. It provides additional arguments to identify the stem cell of some human lymphomas.


Patient education. Developing a health care partnership. Increasingly, patients are insisting on becoming partners in their own health care. Physicians who welcome such involvement should try to determine the medical IQ and knowledge base of the patient and then provide appropriate educational experiences. An atmosphere encouraging genuine dialogue is essential to a successful partnership.


Evidence for RNA synthesis-dependent and -independent pathways in stimulation of neurite outgrowth by nerve growth factor. Studies on the mechanism of action of nerve growth factor (NGF) were carried out with PC12 rat pheochromocytoma cells. PC12 cells are uniquely useful for such studies because they respond to, but (unlike normal neurons) do not require, NGF and may undergo either generation or regeneration of neurites in response to NGF. Regeneration is defined here as NGF-dependent regrowth of neurites within 24 hr after subculture of NGF-treated PC12 cells. As in cultures of normal NGF-responsive neurons, neurite regeneration by PC12 cells occurs even in the presence of high concentrations of RNA synthesis inhibitors. Generation of neurites is defined as the de novo initiation of outgrowth when PC12 cells are exposed to NGF for the first time. In contrast to regeneration, neurite generation takes place with a lag of at least 24 hr and is blocked by low concentrations of RNA synthesis inhibitors. Such findings suggest that there are both RNA synthesis-dependent and -independent pathways in the mechanism whereby NGF stimulates neurite outgrowth. In addition, NGF-treated PC12 cells undergo a time-dependent loss of the capacity for neurite regeneration after pretreatment with RNA synthesis inhibitors or withdrawal of NGF. Such findings suggest that (i) initiation of neurite outgrowth requires NGF-stimulated, RNA synthesis-dependent accumulation of intracellular material(s), (ii) once such accumulation occurs, RNA synthesis-independent regeneration can occur (but only in the presence of NGF), and (iii) the turnover of such material(s) in the absence of their replacement leads to loss of the capacity for regeneration. A tentative sequence is presented for the events whereby NGF may stimulate neurite outgrowth.


H-2 complementation in anti-H-Y cytotoxic T-cell responses can occur in chimeric mice. Cytotoxic T-cell responses against the H-Y antigen in mice are under the control of major histocompatibility complex genes. Not only must cytotoxic T cells recognize both H-Y antigens and "self" H-2K/D molecules to lyse male target cells, but also "appropriate association" between H-Y antigens and H-2K/D antigens is required to induce such cytotoxic responses. Furthermore, it is suggested that appropriate association with H-2-I antigens may also be required to generate H-Y specific helper cells for the cytotoxic response. BALB/c(KdIdDd) mice are nonresponders against syngeneic H-Y antigens, because they lack appropriate associative H-2K/D antigens. This results in the failure of generation of anti H-Y cytotoxic cells, although helper cells may be induced. F1 hybrid mice (BALB/c X C3H/He)F1 or H-2 recombinant mice C3H-OH(KdIdDk) are responders, because H-2Dk (and H-2Kk in the F1) molecules offer appropriate association to H-Y antigens. We here report that allophenic chimeras (H-2d reversible H-2k) and irradiation bone marrow chimeras [H-2d + H-2k leads to F1(H-2d X H-2k)] generate anti-H-Y cytotoxic responses but that cells of the BALB/c(H-2d) genotype comprise most if not all of the cytotoxic cells. A working model is proposed to account for major histocompatibility complex control over anti-H-Y cytotoxic T-cell responses.


Effects of various periods of food deprivation on serotonin synthesis in the lateral hypothalamus. One hr following an infusion of 3H-L-tryptophan, the lateral hypothalamus was perfused with physiological bacteriostatic saline for 40 min. Samples of perfusate, which corresponded to 75--90 min post-infusion, were analyzed by thin layer chromatography for estimation of 3H-labelled L-tryptophan, 5-hydroxytryptophan and 5-hydroxytryptamine. The results indicate that tryptophan uptake and serotonin synthesis are enhanced as a function of hours of food deprivation.


Synergistic action of p-chloroamphetamine and fluoxetine on food and water consumption patterns in the rat. The distribution of eating, drinking and body weight changes during the 24 hr day were examined following brain 5-HT depletion with p-chloroamphetamine (PCA). Following a baseline period, measurements of food and water intakes and body weights were recorded 1, 2, 3, 6, 12, 20 and 24 hr following PCA, 5.0 mg/kg, or saline. Other animals were pretreated with fluoxetine, 10.0 mg/kg, prior to either PCA or saline in an attempt to block the PCA effects. The results indicate acute hypophagia, hypodipsia, and body weight losses. These decreases were not influenced by the time of day when PCA was administered. Pretreatment with fluoxetine enhanced rather than blocked these effects. No long term changes in ingestive behavior were seen. These results are discussed with respect to the possible role of 5-HT in the control of ingestive behavior.


Implementation of the problem-oriented progress note in a skilled nursing facility. Problem-oriented style progress notes were implemented in a skilled nursing facility where problem-oriented medical records were not in use. The problem-oriented note consists of subjective information, objective information, analysis or assessment of the problems, and plan for treatment, and is called a SOAP note. Six physical and occupational therapists used the method of note writing for an eight-week trial period. The author audited the records for errors in using the SOAP note throughout the experimental period. Therapists responded to a questionnaire following the study to assess their attitudes on using the SOAP note. Implementation of the problem-oriented progress note was satisfactory, with the exception of defining the problem list. The therapists reacted positively toward using the problem-oriented method of recording patient progress or status and recommended that its use be taught to physical and occupational therapy students.


A Concord chair for improved contrast ventriculography. This paper describes the adaptation of the G.E.C. Concord X-ray couch for controlled contrast ventriculography. The addition of a chair fixture and head-fixing device coupled with a suitable radiographic procedure has made contrast ventriculography a fairly simple and sure technique.


Cerebellopontine angle tumor: diagnosis by oblique projection vertebral angiography. Oblique projection vertebral angiography is the simplest and most accurate angiographic method of detecting small cerebellopontine angle tumors. The vascular blood supply to the tumor and brainstem is displayed as the surgeon will encounter it during lateral suboccipital craniotomy. The procedure is comfortable for the patient, technically easy to perform, and reproducible. Interpretation is relatively unaffected by variations in vascular anatomy or superimposed vessel or bone images. This method can be used to supplement routine views, or be performed alone with stereoscopic filming.


Factors affecting the development of penicillamine side-effects. Characteristics of patients on penicillamine therapy for rheumatoid arthritis were correlated with the occurrence of different side-effects. Patients developing proteinuria tended to have lower sheep-cell agglutination test titres prior to therapy, but no other correlations were found. It is postulated that rheumatoid factor reacts with immune complexes, causing their precipitation and reducing renal glomerular deposition and therefore the incidence of proteinuria. Penicillamine would surely be the first choice of anti-rheumatic therapy if it were not for its side-effects. It is capable of controlling the disease, but in many cases treatment must be interrupted because of some potentially serious side-effects, such as thrombocytopenia, rash or nephropathy. Understanding the mode of action of a drug may lead to the development of new and better compounds. Similarly, understanding the mechanism of the side-effects may lead to their elimination. This survey was designed to identify factors which influenced the development of particular side-effects in patients receiving penicillamine for rheumatoid arthritis.


Mixed connective tissue disease in children. A diagnosis of Mixed Connective Tissue Disease (MCTD) had been made in five juveniles in the past two years. All have antibodies to the ribonucleoprotein (RNP) component of extractable fluorescence pattern. No child has had life-threatening complications, though three have required steroids to control their symptoms. Antibodies to ENA were looked for in the other sub-groups of Juvenile Chronic Arthritis (JCA); only two of 75 patients with chronic iridocyclitis and antinuclear antibodies had weakly positive tests.


Biochemical characteristics of chronic lymphocytic leukaemia. Glucocorticoid receptors, B and T lymphocyte surface markers, concanavalin A-induced agglutination and thymidine incorporation. Chronic lymphocytic leukaemia (CLL) has a variable clinical course and there is a great need of new prognostic laboratory parameters in this disease. 24 CLL patients were subjected to routine haematological and clinical investigation. The leukaemic cells were analyzed for surface immunoglobulins, complement and sheep red blood cell receptors, Concanavalin A-induced agglutination, cytoplasmic glucocorticoid receptor and for proliferative activity by measurement of tritiated thymidine incorporation. The surface markers studied indicated that all cases were of B-cell origin. Only 5 of 23 patients studied had normal serum immunoglobulin levels. These cases showed a nonprogressive disease. 8 patients had increased infection tendency, all of whom had subnormal IgG levels; 4 of them also had subnormal IgA and IgM and 2 had subnormal IgA levels. 5 out of 6 patients with progressive disease and 3 of 11 with nonprogressive disease had an increased proliferative index, indicating a correlation between this parameter and disease progression. ConA agglutinability was not correlated to disease activity. Cells from 17 of 22 patients showed measurable amounts of glucocorticoid receptor. The 5 patients lacking this receptor had inactive disease.


[Severe alpha 1-antitrypsin deficiency: clinical observations of 21 patients]. The disease course is described in 21 patients with low serum concentrations of alpha1-antitrypsin of the phenotype Z (genotype pi ZZ). 13 of these patients have long-standing disease characterized by bronchitis or dyspnea beginning before the age of 40 and progressing to emphysema (11 patients) and to corpulmonale (7 patients). The remaining 8 patients are children with hepatopathy characterized by prolonged jaundice at birth, persistent hepatomegaly and persistently elevated liver enzymes. In 2 children, the evolution to cirrhosis was ascertained by biopsy.


[A new functional interpretation of malignant lymphomas. The Lukes-Collins classification and its basis]. The revolutionary developments in immunology have profoundly altered our understanding of malignant lymphomas as tumors of the immune system. The current commonly used classifications of non-Hodgkin's lymphomas do not take this new evidence into account and often contain cytologically heterogenous types. The new functional approach to lymphomas and the classification proposed by LUKES and COLLINS in 1974 separate the malignant lymphomas into better defined cytologic types and relate them to the presently known functional lymphocyte subtypes. It is therefore morphologically more accurate and biologically more meaningful than the present Rappaport nomenclature. This review discusses the morphologic and immunologic foundation of the Lukes-Collins concept and compares their classification with the other major currently used nomenclatures, mainly the one of RAPPAPORT. Special reference is made to the Kiel nomenclature which is very similar to the Lukes-Collins approach and is better known in Europe. Technical methods necessary to apply the Lukes-Collins concept are briefly discussed.


An operational model to achieve accountability for social work in health care. This paper describes a social work accountability structure developed and implemented at the Social Service Department of University of Minnesota Hospitals. The structure is founded in a framework derived from Management by Objectives and is composed of the following elements: (a) a transaction-based Management Information System; (b) service definitions developed by the Southern Regional Educational Board; (c) problem identification and record keeping with Problem-Oriented Medical Records; and (d) outcome evaluation through Goal Attainment Scaling. The purpose of the structure is to monitor and document departmental activities, providing feedback reports to staff, management reports to the director, and summary reports to hospital administration. The structure is not a response to a particular set of organizational problems, but an attempt to develop a coherent operational model to guide department development, remaining responsive to future as well as current needs.


The social work stake in problem-oriented recording. Pressure for adoption of Problem-Oriented Recording (POR) is coming from various sources outside of the helping professions: from commercial third-party payers who have a legitmate need to scrutinize claims for payment; from all levels of government, out of concern for cost containment and for decisions regarding the allocation of limited resources; and from consumers and others who demand quality assurance and accountability mechanisms. POR is an ecological approach that promotes the concept of comprehensive health care. As social work is concerned with both the person and his environment, with the causes and the sequelae of illness and the interrelationship of problems, this problem-oriented approach is of immense interest to the profession. The social worker in an ecologically oriented health care system immediately becomes a more significant provider of health care.


Dissociation of factor VIII in the presence of proteolytic inhibitors. When gel filtration of factor VIII is performed with buffers of high ionic strength (1.0 M NaCl or 0.25 M CaCl2), the procoagulant activity elutes with proteins of relatively low molecular weight. It has been suggested that in the presence of proteolytic inhibitors, the procoagulant activity would appear at the void volume. To test this hypothesis, chromatography with buffers of high ionic strength was performed in the presence of benzamidine hydrochloride, soy bean trypsin inhibitor, heparin, DFP, and aprotinin. Under all of these conditions, the procoagulant activity continued to elute with proteins of low molecular weight. Similar findings were obtained after chromatographing cryoprecipitate prepared from the plasma of a normal subject who had received heparin. Thus, at present there is no direct evidence to suggest that proteolysis is involved in the dissociation of factor VIII by buffers of high ionic strength.


Altered factor VIII complexes in patients with acute respiratory insufficiency. Acute respiratory failure is an often-fatal syndrome of multiple etiologies in which altered factor VIII may be a marker of endothelial disease. 12 women with overwhelming viral pneumonia were studied with serial factor VIII antigen, procoagulant activity, and von Willebrand's factor assays. Antigen levels were elevated (range: 86--1644%) out of proportion to procoagulant activity (range: 35--521% by a one-stage assay), and factor VIII antigen to activity ratios were as high as 16:1. Von Willebrand's factor was normal but correlated best with procoagulant activity. All patients had abnormal antigen patterns on crossed immunoelectrophoresis, with increases in protein of both fast and slow mobility. These changes in factor VIII correlated with the patient's clinical courses.


Corneal dystrophies. II. Endothelial dystrophies. In general, endothelial dystrophies present three types of clinical manifestations: 1) production of collagenous tissue posterior to Descemet's membrane which appears as cornea guttata, polymorphic excrescences or gray sheets; 2) a disrupted endothelial mosaic in specular reflection; and 3) corneal edema as a reflection of decreased endothelial barrier and pump functions. In this review, the authors discuss three endothelial dystrophies -- Fuchs', posterior polymorphous and congenital hereditary. They describe the clinical, histopathologic and biochemical features, and illustrate each dystrophy with a composite drawing. Dystrophies of the epithelium, Bowman's layer, and stroma were reviewed separately in the September-October 1978 issue of this journal.


[Internistic risk patients in dental treatment]. From the viewpoint of internal medicine, the author deals with risks encountered in the dental treatment of certain patients. Special attention is paid to local anaesthetics and certain risk factors such as chronic ischaemic disease, pacemaker, hypertension, and circulatory lability. Furthermore, haemorrhages are treated with special regard to haemophilia. The group of the diabetics requires consideration. The significance of endocrine diseases, allergies and vegetative disorders should not be underrated.


[Analysis of hemorrhagic diatheses treated in hospital]. An analysis of the patients hospitalized for haemorrhagic diatheses during the years 1970--1976 leads to the statement that their number had been increasing. It is concluded that the number of stationary treatments might by considerably reduced by regular stomatological check-ups of these patients. Therefore, the authors advocate the establishment of several facilities for regular stomatological check-ups of this group of patients in each district of the GDR.


[The orofacial manifestation of various hemoblastoses]. In everyday practice the stomatologist is sometimes confronted with symptoms that are indicative of malignant diseases. For malignant lymphoma, lymphogranulomatosis and myeloic leucosis, as examples, the authors present in tabular form orofacial symptoms such as bleedings, gingival hyperplasia, ulcerations and others, the occurrence of which requires diagnostic assessment.


Antigens in human monocytes. III. Use of monocytes in typing for HLA-D related (DR) antigens. Monocyte preparations were obtained from the peripheral blood by adherence to plastic dishes. The number of monocytes obtained was significantly greater than the number of B cells recovered from similar samples. Monocytes could be frozen and thawed with relatively little loss in cell numbers or viability. Cytotoxicity tests were performed most reliably at 20 degrees C. Under these conditions, autoantibodies were rare, and normal sera were consistently negative. Serologic reactions obtained with monocytes correlated well with the known specificities of the monocyte panel. Typing results in both normal and diseased populations were similar to results obtained with B lymphocytes. Moreover monocyte cytotoxicity tests were more convenient and easier to read than similar tests performed with B cells.


Structure analysis of small proteins by electron microscopy: valinomycin, bacitracin and low molecular weight cell growth stimulators. Dark field electron microscopy was combined with optical filtering to study at high resolution the structure of the cyclopeptide antibiotics, bacitracin and valinomycin, and two proteins of unknown structure, LMW-CSA N and B, low molecular weight granulocyte colony stimulating activity isolated from medium conditioned with normal or leukemic leukocytes. For bacitracin and valinomycin the images faithfully represented the known structural features at a resolution of 0.5 nm or better, depicting a two-ring structure for bacitracin, as well as the position of the potassium ion in valinomycin. Both proteins of unknown structrue had at least one cyclic peptide portion. LMW-CSA N had a size of 2.0 nm, LMW-CSA B of 2.4 nm. A potential site of the calcium ionophoric activity in the latter protein was found to be in the larger of the two ring portions constituting the molecule.


[Spontaneous rosette test in peptic ulcer of the stomach and stomach cancer]. The authors present the results from the study of the cellular immunoreactivity of immunocompetent lymphoid cells in 23 patients with gastric carcinoma and 30 patients with ulcer disease of the stomach, by applying the test for the confirmation of rosette-forming T-lymphocytes, according to the method of Bach and Lay. A significantly decreased number of T-lymphocytes was found both in case of ulcer disease of the stomach and gastric carcinoma. Best manifested is the depression of the cellular immunoreactivity in gastric carcinoma and it corresponds to the degree of the generalization of the process.


[Coronary heart disease; surgical aspects (author's transl)]. Aspects of indication, of the surgical technique as well as long-term results are discussed on the basis of own experiences in 279 coronary artery operations. Patients suffering from unstable angina pectoris should be operated on as soon as possible. In cases with stable angina pectoris due to a triple vessel disease the long-term results are better with surgery than without.


The effect of serum and allogeneic antiglobulin preparations on the mitogenic reactivity of peripheral blood lymphocytes from patients with rheumatoid arthritis. In vitro transofrmation of peripheral blood lymphocytes (PBL) by phytohaemagglutinin (PHA) and concanavalin A (Con A) was found to be decreased in 17 RA patients. The addition of 50 microliter RA serum or serum from normal controls exhibited an inhibitory effect on the mitogenic reactivity to Con A but not to PHA of both normal and RA patient's PBL. Allogeneic antiglobulin preparations (a-Ig) stimulated the spontaneous in vitro DNA synthesis of PBL from normal control and, to a smaller degree, also from RA patients. The simultaneous addition of a-Ig's and mitogens to PBL of normal controls and RA patients did not exhibit a significant effect on the mitogenic reactivity.


HLA-B27-positive oligarthritis.

HLA-B27-positive oligarthritis. 68 cases with polyarthritis were selected from 406 HLA B 27 positive patients with various rheumatic diseases excluding ankylosing spondylitis (AS) or Reiter's disease. 23 fulfilled at least 5 criteria of the ARA for the diagnosis of rheumatoid arthritis (RA). 5 suffered from polyarthritis and psoriasis. The remaining 40 patients expressed an asymmetric oligarthritis especially of the lower limbs (knee, ankle) affecting predominantly young adult men. Sacroiliitis was observed in 10 cases. Joint erosions, rheumatoid factors and visceral manifestations were uncommon. The arthritic pattern of B 27 positive oligarthritis differed clearly from rheumatoid arthritis (n = 34) and psoriatic arthritis (n = 15), but was similar to peripheral joint involvement in AS (n = 32) except for the higher incidence of coxitis in AS. HLA typing is helpful not only in the early diagnosis of AS but also in the differential diagnosis of unclassifiable polyarthritis.


[Mechanical characteristics of isotonic work and high-energy phosphates in frog ventricle after 1-fluoro-2,4-dinitrobenzene]. The blocking of the creatinphosphokinase by 1-fluoro-2,4-dinitrobenzene (FDNB) allows to investigate the relationship between ATP-supply, contractility and relaxability of the frog's myocardium. In isotonically working isolated ventricles of frogs the time of work, systolic and diastolic volume, velocity of contraction and relaxation as well as the levels of CP, ATP, ADP and AMP were measured at different intervals until termination of each experiment. CP shows a small variation, ATP decreases to 60% and ADP + AMP increase for the same amount under FDNB during the development of a slight inhibition of contractility and a continuously growing inhibition and retardation of relaxation until systolic arrest. ATP content and volume of relaxation correlated strictly. The contracture and the diminished contractility are caused by the decrease of ATP, producing a lack of substrate for Ca transport and actin-myosin-ATPase. This models the course of events during an insufficiency like in angina pectoris and in myocardial infarction.


[6-(2,4-Dinitrophenyl)-mercaptopurine, a stronger immunosuppressive drug than 6-mercaptopurine to primary humoral T-cell dependent immune response in mice]. The suppressive effect of 6-(2,4-Dinitrophenyl)-mercatopurine (DNP-MP) and 6-mercaptopurine (MP) was investigated on the early primary immune response of mice against the T-cell dependent antigens DNP49-bovine gamma globuline (BGG), sheep red blood cells (SRBC) or FITC8-BCG and the T-cell independent DNP22-Ficoll. The number of IgM antibody forming cells (AbFC) to the hapten determinants and to the SRBCs per 10(6) spleen cells was determined. DNP-MP reduced the number of AbFCs after the immunisation with the T cell dependent antigens always stronger than the MP, independently of the antigen type by which the mice had been immunised. The Anti-DNP22-Ficoll immune response was suppressed equally by both immunosuppressive drugs. DNP-MP is not a specific immunosuppressive drug for the anti-DNP-B-lymphocytes. Helper T-cells and macrophages are discussed as target cells for the stronger unspecific action of DNP-MP.


[Concentration and composition of gangliosides in portions of the vertebrate brain]. Studies have been made on gangliosides from various parts of the brain in 5 species of cartilaginous fishes, 2 species of teleosts, 2 amphibian species, 2 avian species and 3 species of mammals. Almost in all the species investigated, the highest content of gangliosides per weight unit of the brain were found in the forebrain (determinations were carried out by sialic acid, sometimes by sphingosine). Ganglioside content of brain structure in warm-blooded animals is higher that in corresponding structures of fishes and amphibia. Comparative studies on ganglioside composition in the brain of fishes and mammals indicate that brain structures exhibit the same pattern of molecular organization, as the whole brain of the species studied (high polysialoganglioside content in teleosts, predominance of gangliosides with a short carbon chain in cartilaginous fishes, etc.). Besides this fact, peculiarities of composition typical of the brain structures were found as well (more polar composition of gangliosides of the cerebellum and some other ones).


[Meningiomas of the 3d cerebral ventricle]. Meningiomas of the third ventricle, especially those located in its anterior part, are a rare occurrence. Two patients with meningiomas of the third ventricle are described. In one of them the tumor was removed successfully. Pneumoencephalography and positive ventriculography are of decisive importance in the diagnosis of these tumors. Analysis of the data in the literature and the authors' personal observations shows that timely removal of these tumors with the use of rational approaches and microsurgical techniques may yield satisfactory results.


[Ventriculography with dimer-X].

[Ventriculography with dimer-X]. The data of ventriculography using a water-soluble contrast medium Dimer-X are discussed. The examination was conducted on 9 patients with tumors. Clear outlines of the ventricular system were demonstrated. The method is distinguished by high informativeness since in demonstrates all parts of the ventricular system simultaneously and makes it possible to study in dynamics the spreading of the contrast medium along the ventricular system with the use of the roentgenotelevision apparatus. The patients endure the examination well.


An electron microscopic investigation on the pathogenesis of human vaginal trichomoniasis. The fine structure of Trichomonas vaginalis and its acid phosphatase activity in the vaginal medium was investigated with the aid of the electron microscope. The relationship among trichomonads, desquamated epithelial cells, macrophages and bacteria was examined with special attention directed towards their phagocytic behavior. Acid phosphatase activity was observed in the Golgi apparatus, phagolysosomes and in the chromatic granules of Trichomonas vaginalis. Macrophages and leukocytes also exhibited activity for acid phosphatase, particularly during phagocytosis. Phagocytosis and digestion of epithelial cells and bacteria by trichomonads was demonstrated. The study of trichomonads in the vaginal medium is considered to be an important approach towards the understanding of the pathogenesis of lesions induced by this parasite.


Circulating B and T lymphocytes in chronic active liver disease. The number of circulating total lymphocytes and the number of B and T lymphocytes from the blood were estimated in 22 patients with biopsy-verified chronic active liver disease. The total number of lymphocytes and the number of rosette-forming cells (T lymphocytes) were decreased in patients with liver disease. The number of IgG,- IgA- and IgM-bearing lymhocytes (B cells) did not change significantly while the number of null cells increased in patients vs. a control group.


T lymphocytes in peripheral blood from patients with neurological diseases. Absolute and relative numbers of T lymphocytes in peripheral blood were determined in 19 different groups of patients with neurological diseases, using the E-rosette test. A significantly decreased total number of T lymphocytes was found in the following groups: acute Guillain-Barré syndrome (GBS), active multiple sclerosis (MS), and malignant cerebral tumor. A less pronounced and not significant reduction was observed in patients with amyotrophic lateral sclerosis (ALS). In all other groups of patients normal total numbers of T lymphocytes were found, thus indicating that the decrease in T lymphocyte counts in GBS, MS and malignant cerebral tumors is not due to nonspecific injury of nerve tissue.


Spheroid degeneration of cornea and conjunctiva. Prevalence among Eskimos in Greenland and Caucasians in Copenhagen. The incidence of spheroid degeneration has been studied in a series of 659 Eskimos from Arctic South-West Greenland and one of 810 Caucasians in Copenhagen with its temperate climate. The over-all prevalence was highest among the Eskimos (12.3% against 4.1% among the Copenhageners, P less than 0.001). The prevalence was found to be independent of sex, but to rise with increasing age (however, with a fall again after the age of 70 years in Copenhagen). The spheroid deposits were present on the conjunctiva in 74%, on the cornea in 18%, and at both sites in 8%. 71% of the subjects displayed autofluorescent globular deposits. These constituted 10% of the total number of globules. The number of globules per subject averaged 30. Spheroid degeneration was rarely found temporally in Eskimos. Spheroid degenerative processes are most frequently seen in pingueculae, but are not considered bear any relation to pterygium.


[Colony-stimulating factor (CSF) and granulopoietic activity (GA) in various mouse organs]. The colony stimulating factor and granulopoietic activity were determined in the homogenates of mouse kidney, liver, spleen and bone marrow. The activity of CSF and GA were highest in the kidney. The homogenate of this organ was fractionated then by ultracentrifugation. The distribution of CSF and GA in subcellular fractions and homogenates may suggest that kidney cells are the source of a substance causing, both, colony stimulation and granulopoietic activity.


Age-related changes of thymus--morphological and functional aspects. The thymus involutes progressively throughout life, beginning at around the sexual maturation. In long-lived BC3F1 hybrid mice, the thymic capacity to induce T cell differentiation begins to decline earlier than the onset of thymic involution, although the magnitude of the decline is different by the subpopulation of T cells. Morphologically, the most active secretory structure seems to be limited exclusively to the neonatal thymus and certain structural changes, reflective of a decline in secretory function, can be detected early in life and they become more pronounced with age. Heterogeneity of thymic epithelial cells is suggested by the facts that age-related and radiation induced decline of immune activities are different in degree by subpopulation of T cells, and the concept is also supported from a morphological viewpoint. It is thus apparent that age-related thymic involution results in decrease of recruitment of fresh capable T cells and increase of old exhausted T cells, eventually bringing about T cell insufficiency in the aged individuals. Such an impaired immune function in the aged mice can be effectively restored by the combined grafting of young bone marrow and newborn thymus, and the thymus is apparently the most limiting factor in the aged. The biological signficance of age-related thymic involution is also discussed.


Visual suppression of caloric nystagmus in cats. A newly devised animal box with which caloric tests can be easily performed in the awake cat is presented. This device is also useful for position and optokinetic tests. Visual suppression of caloric nystagmus was investigated in such vertebrates as monkeys, cats and rabbits. There was a definite species difference in the rate of visual suppression of caloric nystagmus. It may be that the difference among species is due to a difference in fixation function among animal species.


Acquired von Willebrand's disease caused by a monoclonal antibody. A 67-year-old man with malignant lymphoma and acquired von Willebrand's disease is described. His bleeding symptoms started late in life and at this time a monoclonal IgGK serum protein was found. He had a prolonged bleeding time, decreased platelet adhesiveness, low values for factor VIII clotting activity (VIII:C), factor VIII related antigen (VIIIR:Ag) and ristocetin co-factor activity (VIII:Rcof). Infusion of factor VIII concentrates (fraction I-0) did not correct the abnormalities. No inhibitory activity in vitro of the patient's plasma or IgG fraction could be demonstrated against VIII:C, VIIIR:Ag and VIII:Rcof. In order to demonstrate an antibody that binds factor VIII without inhibiting its biological activities in vitro, advantage was taken of the fact that staphylococcal protein A strongly binds the Fc part of IgG molecules. Addition of staphylococci to mixtures of patient IgG and a factor VIII preparation resulted in removal of all factor VIII activities (VIII:C, VIIIR:Ag, VIII:Rcof) from the supernatant at sedimentation of the bacteria. The active binding principle was the M-component, i.e. probably a monospecific antibody molecule. We hypothesize that the complex is formed in vivo and eliminated at an accelerated rate.


Autoantibodies and serum immunoglobulins in chronic liver diseases. In a prospective consecutive study, 68 patients with various liver diseases and 67 control persons were examined for the occurrence of smooth muscle antibodies (SMA), antinuclear antibodies (ANA) and mitochondrial antibodies (MTA) of IgG, IgA and IgM class. A determination of serum immunoglobulins (S-IgG, S-IgA and S-IgM) was also performed. IgG-SMA in titres of greater than 80 occurred in 8 of 12 patients (67%) with hepatitis B antigen (HBag)-negative chronic active liver disease (CALD) and not in other diseases. Apart from one patient with primary biliary cirrhosis (PBC), IgG-ANA in titres of greater than 40 were likewise detected only in HBag-negative CALD (33%). The titres of IgG-SMA and IgG-ANA varied analogously with the biochemical liver parametres. There was a mutual exclusion between HBag and IgG-SMA/-ANA in titres of greater than 20, while IgM-SMA occured in titres of 80 in two patients with HBag-positive CALD. The incidence and titres of IgM-SMA and -ANA were not higher than in the controls. IgA-SMA and -ANA were detected only sporadically. The MTA demonstrated were of IgG PCLASS AND TITRES OF GREATER THAN 40 WERE FOUND ONLY IN PATIENTS WITH PBC (4 of 5). Som of the patients in all groups had an increased conenctration of one or more of the serum immunoglobulins. S-IgG levels were found to be significantly higher in CALD than in the other groups


Embryonic and postnatal development of afferent innervation in cat vestibular receptors. The maturing process of afferent innervation of the vestibular sensory cells in the cat was studied during both the fetal and postnatal stages. Although the type II cells from the 36th day of gestation already have an innervation similar to that found in the adult, it is not the same for the type I receptor cells. Only 75% have a complete innervation from the 7th postnatal day onwards. Most often, the formation of a continuous nerve calyx is caused by the fusion of the neighbouring membranes of the different dendritic elements belonging to the same neuron. Following the polyneuronal innervation of certain type I cells, numerous competition phenomena can be seen between the fibre endings coming from different neurons. The hypothesis that, during ontogenesis, type I cell innervation passes through a stage which corresponds to type II cell innervation is presented in the Discussion.


Vitamin A status of children in Sri Lanka. A representative country-wide rural nutrition status survey determined the extent and distribution of vitamin A deficiency in Sri Lanka in children 6 through 71 months of age. Trained paramedical personnel recorded the presence or absence of selected ophthalmological signs and symptoms associated with vitamin A deficiency in 13,450 children. The results of the country-wide clinical survey indicate that a vitamin A deficiency problem of public health importance may exist in two of 15 health areas. Serum vitamin A levels were determined on 346 survey children from two of 15 health areas and compared with clinical findings for these areas. The lowest mean serum vitamin A, 26.3 microgram/100 ml, occurred in children with clinical eye findings. A high prevalence of clinical eye findings, 34%, and the low mean serum vitamin A value, 28.2 microgram/100 ml, were found in the group of chronically undernourished children--children who are less than 90% of their expected height for age. The survey results enabled planned redirection of the distribution of vitamin A capsules to preschool children in Sri Lanka to areas shown to have the highest prevalences of ophthalmological signs and symptoms and/or the highest prevalence of chronic undernutrition.


Some observations on the in vivo effect of propranolol on platelet aggregation and release. Platelet function was investigated in four normal volunteers, one patient with a mild form of von Willebrand disease, and one with a thrombocytopathy, all taking propranolol. No effect on platelet function attributable to this drug could be demonstrated in any of these subjects. It is suggested that propranolol administered in conventional doses does not impair platelet hemostatic function.


The immunogenicity of dinitrophenylated polyacrylamide and the adjuvant effect of polyacrylamide. Dinitrophenyl-substituted polyacrylamide (PAAm-DNP) is weakly immunogenic in guinea pigs and rats. Only 2-mercaptoethanol-sensitive IgM antibodies are elicited, and no immunological memory in guinea pigs is appreciated. A 15000-fold carrier excess, given 6 days before an immunogenic dose of PAAm-DNP, does not impair the anti-DNP response. Different doses of PAAm failed to increase the level of natural anti-DNP or anti-sulfanilic acid antibodies, either in guinea pigs or rats. Nevertheless, when given together with sheep red blood cells. PAAm increases the anti-sheep red blood cell humoral immune response in rats. It is suggested from the above data that the PAAm-DNP immunogenicity is not accounted for by the 'two-signal' model of B-cell activation (via 'associative antibodies'), nor by a model that ascribes B-cell activation to the polyclonal B-cell activating properties of the carrier. However, the possibility that the adjuvant effect showed by PAAm plays a role in allowing the conjugate PAAm-DNP to be immunogenic, remains an open question, and must be further investigated.


Lymphocyte subpopulations in colo-rectal cancer. Preoperative evaluation. The percentage and absolute numbers of T, T active and B cells determined by rosette and immunofluorescence procedures, together with the lymphocyte response to PHA stimulation, were studied in 50 patients with colo-rectal adenocarcinoma before surgery. In addition, a group of these patients were tested for the presence of circulating CEA. Sixty percent of the patients studied presented a decrease in absolute numbers of T cells. The percentage and absolute number of Ea rosettes were significantly reduced (p less than 0.01), showing a selective loss of the active T cell subpopulations. In 62% of the cases there was a notable decrease in the lymphocyte response to PHA stimulation. There were no significant variations in the B lymphocyte populations. CEA values showed a close correlation with the clinical tumour staging according to the Dukes classification. Pre-operative immunological testing may have prognostic value in tumours of the large intestine and its results can subsequently be used to evaluate the results of surgery and to indicate avenues which may improve and complete the treatment.


The effects of some variable factors on the T and B lymphocyte rosettes. In this study the number of E rosettes increases with an incubation period at 4 degrees C up to 20 to 24 hours. Both EAC and especially E rosettes are shown to be sensitive to mechanical forces; vigorous shaking causes decrease of their number.


Chromosomes and B and T cells in mycosis fungoides. Because mycosis fungoides (MF) and Sézary syndrome (SS) share several features, some investigators have considered them to be different stages of the same disease. Others view them as separate entities. Cytogenetic studies in four typical MF patients showed that the chromosomal abnormalities were different from those reported in SS patients, and the abnormalities were found with almost equal frequency in both B and T cells. In addition, we found the frequencies of the T cells in six of the eight peripheral blood determinations in three patients were within normal range. These observations support the possibility that MF and SS are two separate disease entities.


Tinnitus: diagnosis and treatment.

Tinnitus: diagnosis and treatment. Few conditions are seen as commonly by the otologist and are more poorly understood than subjective tinnitus. Tinnitus has been reported in as high as 80% of patients seen in an otolaryngology practice. This symptom is especially marked in patients with a hearing problem and can be so severe that it becomes incapacitating. Careful diagnosis and classification of tinnitus is important for understanding of the problem. Identification of the frequency and intensity of masking, using a tinnitus analyzer, is useful in selecting the form of treatment. Analysis of the history, physical findings and the use of special electrocochleography and brain stem evoked response audiometry help to identify the site of lesion, which may be within the cochlea, cochlear nerve, cochlear nucleus, brain stem, midbrain or auditory cortex. Specific disease entities should be identified and treated. Lesions of the end-organ or cochlear nerve can be treated when necessary by translabyrinthine or middle cranial fossa section of the cochlear nerve. Tinnitus from cervical nerve lesions can be treated by rhizotomy. The use of a hearing aid or introduction of a sound with a tinnitus masker has been found to be 82% effective in suppressing tinnitus. Maskers can be combined with a hearing aid in some cases. The pathogenesis of tinnitus is discussed, but the method of action of tinnitus relief by auditory stimulation is still unclear. A thoughtful and complete examination with our new diagnostic tools and the judicious selection of therapy now makes it possible to give relief to the majority of patients suffering with disturbing tinnitus.


Vestibular responses to bithermal caloric and harmonic acceleration. Vestibulo-oculomotor responses from 33 patients with either peripheral labyrinthine or central pathology were compared using the standardized Fitzgerald-Hallpike bithermal caloric and harmonic accelerations. In numerous cases (40%), patients with normal caloric responses reflected abnormalities in either their phase relationships or labyrinthine preponderance to sinusoidal acceleration. Results clearly indicate that harmonic acceleration provides additional information to the clinician in the evaluation of vestibulo-oculomotor pathology that is not reflected in the responses to standard caloric tests.


Performance of six sunscreen formulations on human skin: a comparison. Indoor and outdoor tests were performed on human volunteers to determine the protection offered by six commercially available products containing single sunscreen ingredients and combinations of ingredients. Indoor solar simulator studies were performed to determine the inherent efficacy of each product, including use of a whirlpool treatment to evaluate the resistance of each product to wash off. The outdoor study included a ten-minute swimming period followed by sunlight exposure. In all tests, the combination of 7% octyl-dimethyl p-aminobenzoic acid ester and 3% oxybenzone was substantially more effective in protecting against sunburn than any other formula tested, including 5% p-aminobenzoic acid (PABA).


Asymmetry of the internal auditory canals without acoustic neuroma. During the past five years, nine patients with "significant" unilateral enlargement of one internal auditory canal by polytomography were subsequently found to have freely filling canals on contrast posterior fossa myelography. The radiographic appearance of the enlarged canals varied greatly and included all the various configurations usually suggestive of acoustic neuroma. Likewise, the clinical presentation varied greatly from asymptomatic to highly suggesting of cerebellopontine angle tumor. This series underscores the essential nature of posterior fossa studies in the evaluation of potential acoustic neuromas and the variability of the normal architecture of the internal auditory meatus.


Depressed non-specific lymphocyte reactivity in psoriasis. T-lymphocyte number and functions were studied in 24 patients with psoriasis guttata as compared to healthy controls. A decrease was found of the in vitro ability to synthetize DNA in response to stimulation with phytohemagglutinin (PHA), concanavalin A, poke weed mitogen and PPD, which was statistically significant for PHA. The percentage and absolute numbers of both T and B peripheral blood lymphocytes were not altered.


T and B lymphocyte subpopulations in black patients with diabetes mellitus. A modified method of assaying T and B lymphocytes was used to investigate the T and B cell subpopulations in black patients with diabetes mellitus. Thirty-eight black diabetic patients were compared to 55 non-diabetic patients (20 blacks and 35 whites). The diabetic patients had an increased T-lymphocyte population (73.4 percent +/- 7.9) as compared to the black controls (66.2 percent +/- 1.7, p less than 0.001) and the white controls (68.1 percent +/- 3.5, p less than 0.001). Black non-diabetic patients had a decreased T-cell population compared to the white non-diabetic patients. This suggests race was not an explanation for the increased T-cell percentages observed in the diabetic population. No difference was demonstrated in the percentage of B-lymphocyte subpopulations between any group.


Electron microscopic study of thymus and bone marrow derived mouse lymphocytes: morphological differences and evolution of surface markers before and after in vitro mitogenic stimulation. T and B lymphocytes from spleen, lymph nodes, thymus and bone marrow of unstimulated CBA mice have distinct ultrastructural features: respectively the Th type (dense dark appearance, smooth margin, high nucleocytoplasmic ratio, rare cytoplasmic organelles) and the Bm type (low electronic density, villous margin, low nucleocytoplasmic ratio, numerous cytoplasmic organelles). Correlations between Th or Bm morphology and presence of specific T or B surface markers (theta antigen or surface Ig) have been established. The Th/T and Bm/B equivalence do not however hold in all circumstances: first, there are morphologically intermediate types termed In (less than 13%) that may be theta- or Ig-positive; second, some Bm lymphocytes are theta-positive in CBA thoracic duct and some Th lymphocytes are Ig-positive in Nude mice spleen. Purified T-or B lymphocyte populations stimulated by selective mitogens (ConA or LPS respectively) undergo ultrastructural modifications before their surface markers (theta or Ig respectively) disappear. A time, some theta-positive T lymphocytes show a Bm-like morphology. The results suggest that the basis for the usual T-B ultrastructural differences in unstimulated mice resides in the normally different functional state of metabolic activity of these two types of cells: the cell metabolism would be higher in Bm (the usual form of unstimulated B lymphocytes) than in Th (the usual form of unstimulated T lymphocytes). This view may explain the paradoxical results observed in thoracic duct and Nude mice spleen as well as conflicting data reported by several authors.


Ultrastructural detection of Haemophilus ducreyi in biopsies of chancroid. During an endemic appearance of chancroids (26 cases) in Berlin (West) coccobacilli were disclosed in biopsies by electron microscopy. The bacteria were aggregated predominantly in groups in the extracellular space. Their cell wall is approximately 120 A thick and trilaminar as in Gram-negative bacteria. Concerning the cell wall structure and the cytoplasmic composition, the detected coccobacilli are identical to culturally grown Haemophilus ducreyi obtained from chancroids.


[Adherent cell and T lymphocyte cooperation for the "in vitro" production of Brucella-induced interferon by murine spleen cells (author's transl)]. Although Brucella is a good in vivo inducer of interferon, in vitro infection of murine spleen cells by Brucella suis has not, to the present time, led to in vitro synthesis. In the present work we show that normal spleen cells can however synthetize interferon in vitro when cultured together with adherent cells obtained from the spleens of syngeneic mice 45 min after in vivo inoculation. Induction and synthesis are thus shown to be distinct phenomena. Moreover soluble factors are shown to be involved in the induction phenomenon and T cells to be essential for synthesis. This in vitro brucella-induced interferon differs from in vivo brucella-induced interferon: its acid lability and its antigenic properties are characteristic of type II "immune" interferon.


Implications of heterophile antigens in immunological infertility in males. Immunological study was conducted on serum and hydrocel fluids from males belonging to an equatorial African population heavily contaiminated by Filaria and Schistosoma. Anti-spermatozoa antibodies were detected by agglutination in 31 of 64 sera and 24 of 60 fluids, and by cytotoxicity in 19 of 64 sera and 8 of 60 fluids. Antinuclear antibodies were detected in 21 of 64 sera and 8 of 60 fluids. However, the titers of these antibodies were low, as were the frequency and titers of other tissues antibodies. The appearance of antispermatozoa antibodies is also correlated with extensive skin burns and infection by Pseudomonas aeruginosa or severe Candidiasis.


Immunological consequences of vasectomy: I. Prospective study through one-year postvasecotomy. Autoimmunity to sperm developed in two-thirds of men within 1 year after vasectomy as measured by sperm agglutinating and sperm immobilizing antibody tests. Sperm antibody responses to vasectomy were greater in younger than in older men. A direct relationship was apparent between increasing incidence of sperm immobilizing antibody and genetic predisposition to autoimmune disease. Some vasectomized men developed immune responses to autoantigens other than spermatozoa. Increased antithyroglobulin activity was evenly divided between patients who formed sperm antibody and those who did not. Antinuclear activity was more frequent in patients who were sperm antibody responders.


Partial inhibition of the abstinence syndrome in morphine tolerant-dependent mice following pharmacological denervation. Mice were chronically treated with either atropine, methysergide or pentobarbital in order to induce sensitivity changes resulting from adaptative adjustments in the central nervous system (CNS), and to examine the degree of tolerance to and physical dependence on morphine several days after the discontinuation of pretreatments. Subsequently to the chronic blockade of muscarinic or serotonergic receptors, the intensity of tolerance was unaffected, but some manifestations of the abstinence behavior induced by naloxone were reduced in part. This attenuation of the abstinence syndrome in the pretreated mice was reverted by an additional dose of either atropine or methysergide administered a few min before naloxone. Additional experiments with physostigmine or 5-hydroxytryptophan (5-HTP) in morphine-dependent mice yielded results compatible with the hypothesis that morphine physical dependence may be the manifestation of compensatory changes of sensitivity to serotonin and acetylcholine in the CNS. These results do not exclude the participation of other neurotransmitters or neurohormones in morphine dependence.


The acute pharmacologic effects of serotonin on the release of insulin and glucagon in the intact rat. Serotonin (5HT) (5 mg/kg-25 mg/kg; i.p.) induced a dose-related increase of plasma glucagon (IRG) (using 30K antibody) 3 to 60 min after administration to overnight fasted rats. Blood glucose (BS) also increased as early as 10 min post-injection whereas plasma insulin (IRI) increased in a non dose-related (30 min to onset) manner. Adreno-demedullation prevented the rise of BS and IRI, but not IRG. Pretreatment with reserpine (5 mg/kg; i.p.; 24 hr earlier) did not prevent the actions of 5HT. Pretreatment with the alpha-adrenergic antagonist phentolamine (3 mg/kg-6 mg/kg; i.p.) reduced but did not prevent the subsequent rise of IRG, whereas beta-adrenergic blockade with propranolol (5 mg/kg-10 mg/kg; i.p.) was without effect. Phentolamine and the lower dose of propranolol (5 mg/kg) reduced the 5HT-induced hyperglycemia; whereas the higher dose (10 mg/kg) prevented the hyperglycemia. Phentolamine potentiated and propranolol prevented (5 mg/kg) or reversed (10 mg/kg) the 5HT-induced IRI rise. Pretreatment with the 5HT-antagonist, methysergide, prevented all the effects of 5HT. Precursor loading with 5HTP (5 mg/kg-50 mg/kg; i.p.) also resulted in a dose-related increase of IRG and a slight increase of IRI. Blockade of the conversion of 5HTP to 5HT with Ro-4-4602 (an L-aromatic acid decarboxylase inhibitor) blocked the subsequent rise of IRG. These results suggest that the 5HT-induced changes in BS and IRI may be secondary to a release of epinephrine and/or norepinephrine, but that the effects of 5HT on the release of IRG cannot be explained solely by this mechanism.