Lack of effect of levamisole on the immune function in melanoma patients

Summary The immune function of 24 patients with local and regional melanoma receiving levamisole as adjuvant treatment was followed during 12–36 months. There were only minimal changes in the number of the peripheral blood lymphocytes and of E-rosette-forming cells. There was no essential improvement in the responses of peripheral blood lymphocytes to phytohemagglutinin (PHA), concanavalin A (Con A), and purified protein derivative of tuberculin (PPD) during levamisole treatment. Only eight of 24 patients were without recurrence during the observation time of 12–36 months. Our results indicate that adjuvant levamisole therapy in melanoma patients does not exert significant beneficial effects.     

Effect of absolute and relative changes of hematocrit on erythropoiesis in mice

The serial changes of peripheral reticulocytes and marrow erythroid progenitor cells (CFU-e) in mice were monitored under the conditions of absolute or relative changes in red cell mass to study the regulatory mechanism of erythropoiesis. A decreased number of marrow CFU-e and peripheral reticulocytes was observed in the mice with relative polycythemia induced by dehydration as well as in the mice with absolute polycythemia induced by hypertransfusion. On the other hand, a transient increase in the number of marrow CFU-e followed by a gradual increase in the number of peripheral reticulocytes was seen after a considerable amount of exsanguination. Similar stimulatory effects on marrow CFU-e were also observed either by rehydrating the dehydrated mice or by overhydrating the untreated mice to relatively decrease the level of hematocrit. The results suggested that in addition to factors relating to the balance between oxygen supply and requirement, which has been well known, erythropoiesis is greatly affected by hematocrit.     

Cytogenetic changes in the bone marrow cells of long-term irradiated rats]

The occurrence and characteristics of the chromosome structural changes in femur bone marrow cells under continuous irradiation with the exposure rate of 50 R/day within 90 days was followed. The 25% increase in the chromosome aberration frequency was observed within 7 days of the irradiation, and then the aberration rate was constant up to the end of the irradiation (90 days).     

Hemolymph ecdysteroid titer and ecdysteroid-dependent developmental events in the last-larval stadium of the silkworm,Bombyx mori: role of low ecdysteroid titer in larval-pupal metamorphosis and a reappraisal of the head critical period

The endocrine regulation of larval-pupal metamorphosis was studied in the silkworm, Bombyx mori, by measuring the following changes: hemolymph ecdysteroid titer, the secretory activity of prothoracic glands and the responsiveness of larvae to ecdysteroids and prothoracicotropic hormone (PTTH), with regard to developmental events such as the occurrence of spinneret pigmentation, initiation of cocoon spinning and onset of wandering stage as indicated by gut purge. These measurements were concentrated especially on the time before and after the head critical period (HCP) which falls 3-4 days before the gut purge ([Sakurai, 1984]). A small increase in the hemolymph ecdysteroid titer was first found during the HCP, and then the titer increased with daily fluctuations. Small but significant titer peaks were found prior to the occurrence of both spinneret pigmentation and gut purge, indicating that an individual titer peak could possess a specific role in development. Responsiveness of larvae to exogenous 20-hydroxyecdysone (20E) after the HCP was markedly higher than that before the HCP. The sensitivity of the prothoracic gland to PTTH also changed during the HCP. The results thus showed that the HCP is not the period after which an additional PTTH release is not required for the developmental events occurring on schedule, but rather it is the period during which complex events occur not only in the endocrine glands but also in the peripheral tissues. In addition, various developmental phenomena before gut purge are brought about by the hemolymph ecdysteroid whose concentration gradually increased with daily fluctuations, and these precise changes in the titer appeared to be important for the sequential occurrence of developmental events in the larval-pupal metamorphosis.     

The University of Manitoba Follow-up Study. A Prospective Investigation of Cardiovascular Disease: Part II. Build,Blood Pressure and Electrocardiographic Factors Possibly Associated with the Development of Coronary Heart Disease

The relationship of selected physical and electrocardiographic factors to the occurrence of coronary heart disease was examined in a cohort of 3983 healthy North American males followed up for 15 years. Variations in build or mean heart rate were not found to be related to the occurrence of coronary heart disease. The risk of coronary heart disease rose progressively as blood pressure increased. With readings of 160/95 mm. Hg or higher the risk was 1.77 times that of the population as a whole. Non-specific S-T and/or T wave changes in the electrocardiogram were associated with three times the risk of developing coronary heart disease. Individuals with the combination of a blood pressure of 160/95 mm. Hg and nonspecific T wave changes exhibited an augmented susceptibility to coronary heart disease, the risk being four times that of the whole population.     

Hypothalamic potentials evoked by electrical stimulation of the vaginal cervix in the estrous guinea-pig

Summary Evoked potentials were recorded from the hypothalamus of acutely-prepared estrous guinea-pigs responding to electrical stimulation of the vaginal cervix. The latency ranged from 38 to 60 msec. The peak of the first positive wave appeared 50 to 90 msec after the stimulation, usually followed by a negative wave in 120 msec. These responses were obtained from the mid-hypothalamus. The cervical stimulation subsequently induced the release of hypophysial luteotropin (LTH) as indicated by the occurrence of pseudopregnancy. According to the results, the mechanism triggering hypothalamic potential changes was discussed in connection with the LTH secretion.Research Fellow of the Alexander von Humboldt-Foundation in 1967/68.     

The value of the fluorescence histochemistry of biogenic amines in neurotoxicology

Conclusions Acid- and aldehyde-induced fluorescence offers a highly sensitive and specific instrument for the histochemical demonstration of biogenic amines. This technique can be used to advantage for the selective identification of those neuronal structures that contain biogenic amines, namely the peripheral postganglionic sympathetic neurones and the central aminergic neuronal systems.Structural changes of impaired aminergic neurones can be ascertained from their fluorescence microscope image and correlated with light and electron microscopical observations, so that selective neurotoxic changes, such as sympathetic denervation of organs, can be detected and the reversibility of these changes tested.The degree of functional and structural changes occurring in the above neuronal systems can be easily quantified by means of microfluorimetry.The histochemical approach is restricted by the necessity of using fresh and specially fixed tissues. The possibility of numerous pitfalls in the interpretation of histochemical reactions requires the simultaneous use of other optical methods, such as light and electron microscopy, or the testing of the uptake of exogeneous amines or their precursors, whenever the occurrence of neurotoxic effects is to be assessed.     

Regeneration restores some of the altered electrical properties of axotomized bullfrog B-cells

In bullfrog B-type sympathetic neurones axon injury produces substantial changes in somal membrane properties. These include a shortening of action potential afterhyperpolarization (AHP) and an increase in action potential (AP) duration. In the present experiments we compared two injury situations: nerve crush, which was followed by regeneration, and nerve cut, after which regeneration to the original target was prevented, to investigate whether these electrophysiological changes were related to axon regeneration. Both crush and cut injuries produced a similar maximum decrease in AHP duration (to 33 and 30%) by 14 days after axotomy. After nerve crush, AHP duration recovered to within control values by 42 days, while after cut it remained depressed. AHP amplitude decreased to the same extent after nerve crush or cut (to 62 and 58%), but the rate of decrease was slower following crush when compared with cut, and following both types of injury it still remained depressed at 42 and 49 days. Changes in AP duration also took longer to occur following nerve crush, reaching maximal values at 35-42 days, at which time AHP duration had returned to within the normal range. The early reduction in AHP duration and its rapid recovery in regenerating neurones suggests that the current underlying this membrane property is regulated by events associated with axon outgrowth and peripheral reconnection. In contrast, changes in AHP amplitude and AP repolarization appeared to be independent of the occurrence of axon regeneration and remained abnormal at 49 days despite the recovery of AHP duration. These results imply that the electrophysiological changes seen in B-cells following injury are differentially regulated during subsequent regeneration.     

Long-term survey data (1965-1972) on the occurrence of Anisakis larvae (Nematoda: Ascaridida) in herring, Clupea harengus L., from the North Sea

The occurrence of larval Anisakis in North Sea herring was examined during the period 1965-1972 using a sampling method which yielded comparable data for all eight years. Data on abundance of infestation in several herring stocks pointed to remarkable fluctuations over the study period with an increase in the period 1966-1968 followed by a decrease in the period 1968-1972. Of various hypotheses that may explain this situation, it is concluded that changes in the migration behaviour of the herring may be responsible. Other data and statistics are discussed with special reference to variations in infestation level in different samples and to the occurrence of adult nematodes in marine mammals.     

Early changes in peripheral blood T cells during primary infection of rhesus macaques with a pathogenic SIV

Primary infection of rhesus macaques with pathogenic strains of simian immunodeficiency virus (SIV) leads to rapid and dynamic changes in both viral load and T cell counts in the peripheral blood. We have performed a sequential analysis of peripheral blood CD4 and CD8 T cells in five macaques during the 8 weeks following SIVmac251 infection. We observed a transient lymphopenia of both CD4 and CD8 T cells during the first 2 weeks, followed by a rebound. The primary phase of infection was associated with changes in the T cells expressing CD25, CD69, or HLA-DR and with a priming of the peripheral blood CD4 and CD8 T cells for a process of apoptosis in vitro that was enhanced by CD95 (Fas) ligation, and was detected in two macaques as early as 7 days after infection. Despite the small numbers of animals studied, the importance of the early transient CD4 and CD8 T lymphopenia was positively correlated with the viral load. No correlation was found, however, between the level of activation markers expressed or of priming for apoptosis in peripheral blood T cells and the viral load. Our findings suggest the possibility that the early activation and priming for apoptosis of CD4 and CD8 T cells may involve indirect, host-related, mechanisms, or alternatively, that the T cells that remain in the peripheral blood during primary infection do not adequately reflect the viral-mediated changes in T cell activation and death that may occur in the lymphoid organs throughout the body.     

Early changes in peripheral blood T cells during primary infection of rhesus macaques with a pathogenic SIV

Primary infection of rhesus macaques with pathogenic strains of simian immunodeficiency virus (SIV) leads to rapid and dynamic changes in both viral load and T cell counts in the peripheral blood. We have performed a sequential analysis of peripheral blood CD4 and CD8 T cells in five macaques during the 8 weeks following SIVmac251 infection. We observed a transient lymphopenia of both CD4 and CD8 T cells during the first 2 weeks, followed by a rebound. The primary phase of infection was associated with changes in the T cells expressing CD25, CD69, or HLA-DR and with a priming of the peripheral blood CD4 and CD8 T cells for a process of apoptosis in vitro that was enhanced by CD95 (Fas) ligation, and was detected in two macaques as early as 7 days after infection. Despite the small numbers of animals studied, the importance of the early transient CD4 and CD8 T lymphopenia was positively correlated with the viral load. No correlation was found, however, between the level of activation markers expressed or of priming for apoptosis in peripheral blood T cells and the viral load. Our findings suggest the possibility that the early activation and priming for apoptosis of CD4 and CD8 T cells may involve indirect, host-related, mechanisms, or alternatively, that the T cells that remain in the peripheral blood during primary infection do not adequately reflect the viral-mediated changes in T cell activation and death that may occur in the lymphoid organs throughout the body.     

Microcirculatory changes in the cheek pouch mucosa of hamsters in the dynamics of experimental traumatic shock]

Acute experiments conducted on hamsters demonstrated significant disturbances of the microcirculation in the mucosa of the cheek pouch during a severe traumatic shock after a standardized mechanical injury of the hip. All the animals died in the course of the first 24 hours after this trauma. If the animals died not earlier than in one hour after the trauma the microcirculation changes were distinctly phasic in character; particularly there was seen a phase of temporary relative adaptation and stabilization of the peripheral circulation, invariably followed by the phase of decompensation, the terminal phase and death. In cases with a rapid lethal issue in the course of one hour no distinct phasic character of the microcirculation changes was observed, but there was a more or less rapid aggravation of all he indices. In difference from the majority of other investigators, no marked intravascular erythrocyte aggregation was seen by the authors in the experiments described.     

Status of hemapoiesis in residents of the Techa riverside villages in the period of maximum radiation exposure. Report 1. Evaluation of the cellular composition of peripheral blood and the role of comorbidities in the oppression of hemapoiesis

Residents of the Techa riverside villages chronically exposed to ionizing radiation (the average dose rate in 1951-1956 was 0.047 Gy/year, the maximum reached 2.44 Gy/year) developed marked changes in the cellular composition of peripheral blood. The maximum reduction of peripheral blood counts occurred in the years 1951-1953, after which the beginning of the restoration of cellularity to the control level was observed. The dose rate at this point (1956) was about 0.02 Gy/year. The factors of radiation and non-radiation nature (gender, the age at the onset of exposure, health related disorders) in different combinations affect the number of peripheral blood cells. The influence of dose rate of a chronic radiation exposure on a platelet count takes precedence over other factors. The factors of gender and dose rate determine the number of erythrocytes in exposed persons. The changes accompanying the health status and dose rate significantly affect the number of neutrophils. The influence of comorbidity, age and dose rate on the number of monocytes was noted. A lymphocyte count was mainly determined by the age at the onset of exposure and concomitant diseases. A joint influence of chronic radiation exposure and concomitant diseases increases a mutual action on erythro- and thrombocytopoiesis. The decrease of the dose rate was followed by a gradual predominance of the somatic disease influence on leukocyte (neutrophils, lymphocytes and monocytes) counts.     

Change in the alkaline phosphatase activity and glycogen content in the leukocytes of white rat blood under the influence of penicillin preparations]

The contents of alkaline phosphatase and glycogen in the neutrophils of the peripheral blood of unbred albino rats weighing 170-200 gm were determined. Benzylpenicillin and oxacillin in doses of 50000 and 20000 Units/kg respectively were administered intramuscularly once a day over a long period of time. Two-phase changes in the contents of alkaline phosphatase and glycogen under the effect of penicillin were found. An increase in their contents was observed on the 5-10th days then it was followed by a decrease. Increase in the contents of the metabolites proceeded simultaneously with enhancing of the digestive capacity of the leucocytes and activity of lysozyme in them.     

Seasonal changes of humoral and cellular immune responses to Japanese cedar (Cryptomeria japonica) pollen allergens in Japanese monkeys (Macaca fuscata) with pollinosis

The natural occurrence of Japanese cedar [Cryptomeria japonica (CJ)] pollinosis has been reported in Japanese monkeys (Macaca fuscata). The present study was designed to investigate seasonal changes in immunological reactions to CJ pollen allergens in monkeys with CJ pollinosis. Blood samples were collected from six monkeys with CJ pollinosis before and after CJ pollen season. Seasonal changes in specific IgE and IgG to major allergens (Cry j 1 and Cry j 2) were observed before and after CJ pollen season. The humoral responses decreased significantly before CJ pollen and increased after CJ pollen season. Similar seasonal changes in peripheral blood mononuclear cells proliferative responses to CJ allergens were observed before and after CJ pollen season. These humoral and cellular immune responses might serve as a biomarker for assessing new immunotherapies for monkeys with pollinosis.     

Ultrastructural differences during embryonic cell death in normal and peripherally deprived ciliary ganglia

Normally occurring neuron death and that brought about by prior removal of the peripheral target organ was studied ultrastructurally in embryonic chick ciliary ganglion in order to better understand the mechanism of cell death in this system. Before the period of cell death, all neurons in the normal ganglion developed a well-organized rough endoplasmic reticulum (RER) which coincided with peripheral synapse formation. None of the peripherally deprived neurons underwent this change, suggesting that some interaction with the periphery, possibly synapse formation, triggered them into the secretory state. Cell death in peripherally deprived neurons was signalled by nuclear changes followed by freeing of ribosomes from polysomes and RER and presumably cessation of protein synthesis. In contrast, normal cell death was brought about by dilation of the RER with eventual cytoplasmic disruption, nuclear changes appearing only secondarily. It is suggested that failure to form or maintain peripheral synapses could result in the accumulation of transmission-related proteins with consequent cisternal dilation, and eventual cell death.     

Effects of removal in late pregnancy of the corpus luteum, graafian follicle or ovaries on plasma progesterone, oestradiol, LH, parturition and post-partum oestrus in the tammar wallaby, Macropus eugenii

Concentrations of oestradiol-17 beta, progesterone, and luteinizing hormone (LH) were measured in plasma collected at 6- to 12-h intervals from tammars around the time of parturition and post-partum oestrus. Parturition occurred on Day 26 or 27 after reactivation of lactation-delayed pregnancy and coincided with a precipitous decline in progesterone levels. A sharp rise in oestradiol, from basal concentrations of less than 10 pg/ml to a peak of 13 to 32 pg/ml, as well as oestrus, followed the drop in progesterone by 8.3 and 9.8 h, respectively. The LH surge was dependent on the oestradiol rise and followed it by 7 h. Ovulation followed mating by about 30 h and the LH surge by 24 h. Removal of the ovary with the large Graafian follicle prevented the oestradiol rise, oestrus and the LH surge, but not parturition. Peripartum changes in peripheral oestradiol do not appear to be involved in initiation of parturition but the oestradiol rise and associated change in the oestradiol:progesterone ratio are important signals for post-partum oestrus and the LH surge.     

Changes in the blood system after its extracorporeal irradiation

One-stage extracorporeal beta-radiation of dog blood in a dose of 6-12 Gy is not followed by the development of radiation after-effects. Favourable changes in the peripheral blood content are marked. Erythrocyte carbohydrates undergo adaptation reconstruction with an increase in the percentage of nucleic acids. Over 7 to 30 days of observation the activity of nonspecific immunity factors such as lysozyme, lytic activity of beta-lysines, and phagocytosis also increases. At the same time the antimicrobial action of penicillin is potentiated. The data obtained can be used for correction of upset immune responsiveness.     

Spontaneous beat-by-beat fluctuations of total peripheral and cerebrovascular resistance in response to tilt

Beat-by-beat estimates of total peripheral resistance (TPR) can be obtained from continuous measurements of cardiac output by using Doppler ultrasound and noninvasive mean arterial blood pressure (MAP). We employed transfer function analysis to study the heart rate (HR) and vascular response to spontaneous changes in blood pressure from the relationships of systolic blood pressure (SBP) to HR (SBP-->HR), MAP to total peripheral resistance (TPR) and cerebrovascular resistance index (CVRi) (MAP-->TPR and MAP-->CVRi), as well as stroke volume (SV) to TPR in nine healthy subjects in supine and 45 degrees head-up tilt positions. The gain of the SBP-->HR transfer function was reduced with tilt in both the low- (0.03-0.15 Hz) and high-frequency (0.15-0.35 Hz) regions. In contrast, MAP-->TPR transfer function gain was not affected by head-up tilt, but it did increase from low- to high-frequency regions. The phase relationships between MAP-->TPR were unaffected by head-up tilt, but, consistent with an autoregulatory system, changes in MAP were followed by directionally similar changes in TPR, just as observed for the MAP-->CVRi. The SV-->TPR had high coherence with a constant phase of 150-160 degrees. Together, these data that showed changes in MAP preceded changes in TPR, as well as a possible link between SV and TPR, are consistent with complex interactions between the vascular component of the arterial and cardiopulmonary baroreflexes and intrinsic properties such as the myogenic response of the resistance arteries.