Environmental contaminants and intestinal function. THE ENVIRONMENTAL CONTAMINANTS WHICH HAVE THEIR MAJOR EFFECTS ON THE SMALL INTESTINE MAY BE CLASSIFIED INTO FIVE MAJOR CATEGORIES: (1) bacterial, viral, and parasitic agents, (2) food and plant substances, (3) environmental and industrial products, (4) pharmaceutical agents, and (5) toxic agents whose metabolic effects are dependent on interreaction with intestinal bacterial flora, other physical agents (detergents), human intestinal enzyme deficiency states, and the nutritional state of the host.Bacterial, viral, and parasitic agents are the most important of all such agents, being responsible for significant mortality and morbidity in association with diarrheal diseases of adults and children. Several plant substances ingested as foods have unique effects on the small bowel as well as from contaminants such as fungi on poorly preserved grains and cereals. Environmental and industrial products, in spite of their widespread prevalence in industrial societies as contaminants, are less important unless unexpectedly intense exposure occurs to the intestinal tract. Pharmaceutical agents of several types interreact with the small bowel mucosa causing impairment of transport processes for fluid and electrolytes, amino acid, lipid and sugars as well as vitamins. These interreactions may be dependent on bacterial metabolic activity, association with detergents, mucosal enzyme deficiency state (disaccharidases), and the state of nutrition of the subject.


Intestinal disease and the urban environment. Factors in the urban environments of highly industralized societies are important causes of disease. This review examines urban diseases of small and large intestine. The urban environment is pervaded by chemicals including drugs, food additives, pesticides, industrial products, etc., which are potential causes of disease. Examples of typical urban, as contrasted with rural, intestinal disease are considered in terms of differing etiological factors. Urban intestinal disease is examined from the following standpoints: the population at risk; the chemical agents to which the population is exposed; a model for the physiology of distribution and metabolism of chemicals in relation to the alimentary tract; the application of this model to treatment of an industrial disease; a major urban disease of the alimentary tract, carcinoma of the colon, considered in terms of this model; approaches to characterizing, identifying, and controlling urban intestinal disease.


Health and environmental impacts of increased generation of coal ash and FGD sludges. Report to the Committee on Health and Ecological Effects of Increased Coal Utilization. This paper focuses on the incremental impacts of coal ash and flue gas desulfurization (FGD) wastes associated with increased coal usage by utilities and industry under the National Energy Plan (NEP). In the paper, 1985 and 2000 are the assessment points using the baseline data taken from the Annual Environmental Analysis Report (AEAR, September 1977). In each EPA region, the potential mix of disposal options has been broadly estimated and impacts assessed therefrom. In addition, future use of advanced combustion techniques has been taken into account. The quantities of coal ash and FGD wastes depend on ash and sulfur content of the coal, emission regulations, the types of ash collection and FGD systems, and operating conditions of the systems and boiler. The disposal of these wastes is (or will be) subject to Federal and State regulations. The one key legal framework concerning environmental impact on land is the Resource Conservation and Recovery Act (RCRA). RCRA and related Federal and State laws provide a sufficient statutory basis for preventing significant adverse health and environmental impacts from coal ash and FGD waste disposal. However, much of the development and implementation of specific regulations lie ahead. FGD wastes and coal ash and FGD wastes are currently disposed of exclusively on land. The most common land disposal methods are inpoundments (ponds) and landfills, although some mine disposal is also practiced. The potential environmental impacts of this disposal are dependent on the characteristics of the disposal site, characteristics of the coal ash and FGD wastes, control method and the degree of control employed. In general, the major potential impacts are ground and surface water contamination and the "degradation" of large quantities of land. However, assuming land is available for disposal of these wastes, control technology exists for environmentally sound disposal. Because of existing increases in coal use, the possibility of significant environmental impacts, both regionally and nationally, exists regardless of whether the NEP scenario develops or not. Existing baseline data indicate that with sound control technology and successful development and implementation of existing regulatory framework, regional scale impacts are likely to be small; however, site-specific impacts could be significant and need to be evaluated on a case-by-case basis. Both Federal and privately-funded programs are developing additional data and information on disposal of FGD sludges and coal ash. Continuation of these programs will provide additional vital information in the future. However, further information in several areas if desirable: further data on levels of radionuclides and trace metals in these wastes: studies on biological impacts of trace metals; and completion of current and planned studies on disposal problems associated with advanced combustion techniques like fluid bed combustion.


Methods for the analysis of intestinal function. The intestinal tract, an organ of considerable complexity, requires application of numerous techniques for analysis of its physiology and perturbations by toxicologic agents. This review describes the methodology of importance in analysis of the absorptive function of the intestine and the transit of intestinal contents. Methods for studying absorption are categorized according to the technique for administering the test substance such as inclusion in the diet or by gastric and intestinal placement and the method of quantitating the degree of absorption such as determining the appearance of a test substance in systemic fluids or its disappearance from its site of administration in the intestine. In vitro techniques which have no in vivo analogs, such as the use of the everted sac, are briefly described and their limitations emphasized. Procedures of importance in the clinical diagnosis of malabsorption or in the experimental analysis of absorptive function in man are included and distinguished from techniques used in animal models. In addition, methods for studying aspects of gastrointestinal motility, including the use of luminal markers and analysis of the contractile and electrical activity of intestinal smooth muscle, are reviewed.


Acid mine drainage and subsidence: effects of increased coal utilization. The increases above 1975 levels for acid mine drainage and subsidence for the years 1985 and 2000 based on projections of current mining trends and the National Energy Plan are presented. No increases are projected for acid mine drainage from surface mines or waste since enforcement under present laws should control this problem. The increase in acid mine drainage from underground mines is projected to be 16 percent by 1985 and 10 percent by 2000. The smaller increase in 2000 over 1985 reflects the impact of the PL 95-87 abandoned mine program. Mine subsidence is projected to increase by 34 and 115 percent respectively for 1985 and 2000. This estimate assumes that subsidence will parallel the rate of underground coal production and that no new subsidence control measures are adopted to mitigate subsidence occurrence.


Potential health and environmental effects of trace elements and radionuclides from increased coal utilization. This report addresses the effects of coal-derived trace and radioactive elements. A summary of our current understanding of health and environmental effects of trace and radioactive elements released during coal mining, cleaning, combustion, and ash disposal is presented. Physical and biological transport phenomena which are important in determining organism exposure are also discussed. Biological concentration and transformation as well as synergistic and antagonistic actions among trace contaminants are discussed in terms of their importance in mobility, persistence, availability, and ultimate toxicity. The consequences of implementing the President's National Energy Plan are considered in terms of the impact of the NEP in 1985 and 2000 on the potential effects of trace and radioactive elements from the coal fuel cycle. Areas of needed research are identified in specific recommendations.


Health effects of coal mining and combustion: carcinogens and cofactors. Some polynuclear aromatics (PNA) have been found to be potent carcinogens for all tissues and organs of experimental animals that have been exposed to them, but different dose levels are needed for these effects. They have been known for decades to cause cancer at the site of application but also at certain sites distant from the area of contact. Although some hydrocarbons are potent and complete carcinogens, the majority of related hydrocarbons was originally found to be inactive. Since they generally appear together, it was important to know more about their interaction, particularly whether they would synergize, or antagonize. The polycyclic hydrocarbons have been studied by subcutaneous injection, where they prove very potent carcinogens. They are also very active on the skin of mice where they produce cancer on prolonged application. Inhalation studies, require larger doses yielded negative results until particulate matter was introduced which facilitated the development of lung tumors. Although iron oxide dust was used initially, other dusts were also capable of enhancing the response of the tissue to benzo(a)pyrene carcinogenesis. This point is of importance, particularly since the inhalation of PNA in situations of air pollution or coal mining involves particulates, although of a different type. Soot is not a homogenous substance and several factors determine its properties. Soots will lose some of the absorbed chemicals during their residence in air, but they retain their PNAs for long periods of time when they reach the soil. The carcinogenicity of PNAs in the adsorbed state may be completely absent, depending on particle size of the soot and availability of eluting capability of the tissues or cells in contact with the soot. Whenever the carcinogenic polynuclear aromatics can be eluted they will be active in producing cancer if their residence is adequate. There seems to be no reason to assume that a large increase in coal combustion in the future will by necessity lead to greater risks of cancer to the coal miners or the general urban dweller, because activities to be started now can take into consideration the requirements necessary for control of air pollution in mines as well as in cities. If new uses of coal will be developed, it will be a completely different situation, and statements about the carcinogenic risk from coal utilization do not apply there. Although some of the same carcinogenic PNAs are involved in the health hazards from those processes, other carcinogens and also cocarcinogens will be present, and the exposed workers will not have the apparent benefits of adsorption of PNAs on soot.


Intestinal metabolism.

Intestinal metabolism. The anatomy of the intestine is outlined. The kinetics of cell proliferation, differentiation, and migration in intestinal epithelium are described. The distribution of cell types between the proliferation and differentiation compartments of the epithelium is summarized. Seven preparations of intestine in current use for metabolic studies are listed. An outline review is presented of recent results on glucose, amino acid and ketone body metabolism obtained with three of these preparations: the ligature-isolated loop of intestine in vivo; the vascularly and luminally perfused intestine in vitro; and suspensions of respiring intestinal epithelial cells in vitro. Reasons are given for thinking that these experimental systems are among the most useful currently available for metabolic studies, perhaps especially in the investigation of the metabolic fate of potentially toxic materials to which animal species may be exposed.


Occupational safety and health implications of increased coal utilization. An area of major concern in considering increased coal production and utilization is the health and safety of increased numbers of workers who mine, process, or utilize coal. Hazards related to mining activities in the past have been especially serious, resulting in many mine related accidental deaths, disabling injuries, and disability and death from chronic lung disease. Underground coal mines are clearly less safe than surface mines. Over one-third of currently employed underground miners experience chronic lung disease. Other stresses include noise and extremes of heat and cold. Newly emphasized technologies of the use of diesel powered mining equipment and the use of longwall mining techniques may be associated with serious health effects. Workers at coal-fired power plants are also potentially at risk of occupational diseases. Occupational safety and health aspects of coal mining are understood well enough today to justify implementing necessary and technically feasible and available control measures to minimize potential problems associated with increased coal production and use in the future. Increased emphasis on safety and health training for inexperienced coal miners expected to enter the work force is clearly needed. The recently enacted Federal Mine Safety and Health Act of 1977 will provide impetus for increased control over hazards in coal mining.


Intestinal structure and function related to toxicology. The study of toxic effects on small intestinal function is complicated by the integration of the activity of the small intestine with the activities of other regions of the GI tract. Also, the barrier and portal functions of the intestine are not as clearly defined as sometimes assumed. The intestinal surface functions as a barrier to the ingress of large quantities of large water soluble molecules. Lipidic substances enter the body quite readily as do small water-soluble molecules. The small intestinal surface is more a portal than a barrier, with its portal functions divided between nonspecific diffusional entry, which depends on physical properties and electric charge, and entry by specific membrane transport, which depends upon chemical structure. The implications of these properties of the small intestine for toxicological studies are stressed.


Thermal pollution consequences of the implementation of the president's energy message on increased coal utilization. The thermal consequences of coal utilization are most meaningfully assessed in comparison with the form of power generation replaced by coal which is most likely nuclear. The different effects are influenced by siting decisions and the intrinsic thermal efficiencies of the two fuel systems. Nuclear power plants discharge 50% more waste Rheat to the atmosphere through cooling towers or to a water body than coal-fired plants. Coal-fired plants require about 2/3 as much water as nuclear power plants. Nearly every property of water is affected nonlinearly by temperature, and biological effects may amplify these changes because protein denaturation takes place more rapidly above 30 degrees C and these high temperatures affect bactericidal and viricidal activity of chlorine compounds. Usually algal populations change from a dominance of diatoms and green algae to dominance by blue-green algae. All organisms experience elevated metabolic rates at higher temperatures which may affect total energy needs, foraging ability, reproduction, migration and susceptibility to disease. Intake structures inevitably draw many organisms into the cooling system of a power plant, but the number and kind are influenced by its location, configuration, and mode of operation. Use of water recirculation systems reduces water use and with it, the number of organisms entrained. Mechanical damage in the cooling system to small organisms is generally low, but fish and their larvae and eggs may be seriously damaged. Discharge effects may also be severe but are generally local. The near field, where there are strong shear velocities and rapid temperature changes are particularly stressful to fish, and stringent limitations on the timing and strength of discharges may be required to reduce these stresses to nondamaging levels. Off-stream cooling systems may increase cloudiness, ground fog, precipitation, temperature and local winds, but these effects generally extend no further than 1000 m even in winter. There is considerable potential for using condenser cooling water for agricultural and aquacultural purposes such as irrigation, frost protection, undersoil heating, greenhouse heating and climate control. However, over the next few decades little of this waste heat is likely to be used creatively. The thermal consequences of implementing NEP are locally serious but do not pose regional problems. Creative use of the waste heat for aquaculture, agriculture, cogeneration, and power for energy intensive industries can be a powerful means of mitigating undesirable effects.


Intestinal transport: studies with isolated epithelial cells. Isolated intestinal epithelial cells have been extremely useful for characterizing the nature of intestinal absorption processes and for providing insight into the energetics of Na(+)-dependent transport systems. This report describes a number of experimental approaches which have been used for investigating the specific epithelial transport systems involved in sugar absorption, but provides information which ultimately should prove useful for characterizing a number of different intestinal transport events. Similar experiments should also prove useful for exploring the effect of environmental agents on the function of intestinal tissue. In the case of sugars, net absorption is accomplished via a mucosal, Na(+)-dependent concentrative transport system acting in sequence with a passive serosal system which does not require Na(+). The serosal system limits the full gradient-forming capability of the muscosal system. Agents such as phloretin or cytochalasin B which inhibit serosal transport allow the cells to establish sugar gradients as high as 70 fold in contrast to 10-15 fold gradients observed for control cells. Seventy-fold sugar gradients cannot be explained in terms of the energy available in the electrochemical potential for Na(+) if the Na(+):sugar coupling stoichiometry is 1:1 as commonly assumed. New information indicates that the true Na(+):sugar stoichiometry is in fact 2:1. Flow of two Na(+) ions per sugar molecule down the transmembrane electrochemical potential for Na(+) provides more than sufficient energy to account for observed 70 fold sugar gradients. If flow of sugar by other routes could be completely inhibited, theoretical sugar gradients as high as 400 could be achieved assuming that the cells maintain a membrane potential of -36 mV as measured for intact tissue.


Lipid absorption and metabolism.

Lipid absorption and metabolism. Metabolic processes occurring within the mucosal cell are critical in determining results of interactions between environmental agents and the alimentary tract. The absorption, metabolism, and transport of lipids affects most those agents which are lipid soluble. The understanding of the process involved in lipid absorption and transport is therefore important for both appreciation of the mechanism of uptake of these toxins and for an effective interference with it. Most of the detailed mechanisms of lipid absorption and transport have been proposed from in vitro studies with soluble cell-free systems. The present review integrates these results with recent in vivo and in vitro findings with intact animal tissues and isolated mucosal cells. While there is much general agreement occasional startling differences are also observed, which may have a bearing on the mechanism of normal fat absorption and on the understanding of the transport of the fat-soluble toxins across the mucosal villus cell.


Intestinal absorption and metabolism of xenobiotics. There are five possible processes of intestinal absorption of xenobiotics. These are active transport, passive diffusions, pinocytosis, filtration through "pores," and lymphatic absorption. The passive diffusion is major process for transport of foreign chemicals across the intestine. Though the lymphatic absorption of drugs is not of any major therapeutic significance, the uptake of toxic chemicals such as 3-MC, benzpyrene, and DDT through lymphatics may enhance their toxicity, since they are distributed to other organ systems in the body without being metabolized by liver. A number of factors such as diet, motility of intestine, interference with gastrointestinal flora, changes in the rate of gastric emptying, age of the animal, and dissolution rate of xenobiotic can alter the rate of absorption of chemicals. Liver is the major site of metabolism of xenobiotics, but the contribution of intestinal metabolism of xenobiotic can influence the overall bioavailability of chemicals. The xenobiotic metabolizing enzymes located in endoplasmic reticulum of intestine possess biochemical characteristics similar to that of liver. In general, the rate of metabolism of xenobiotics by intestinal microsomal preparation is lower than that observed with similar hepatic microsomal preparations. The in vitro intestinal metabolism of xenobiotics is affected by several factors including age, sex, diurnal variations, species, and nutritional status of the animal. The intestinal xenobiotic metabolizing enzymes are stimulated by the pretreatment of animals with foreign chemicals, but this depends on the route of administration of chemicals, drug substrate and the animal species used. Rabbit intestinal drug metabolizing enzymes seem to be resistant to induction by foreign chemicals.


Properties and biological significance of the ileal bile salt transport system. The properties of a specific transport system for bile salts, which is located in the ileum of the small intestine are described. The system operates by a sodium ion cotransport mechanism, and it functions in maintaining a normal enterohepatic circulation of bile salts. Analysis of structure-activity data allows us to depict our hypothesis for the interaction of bile salt and Na with the membranal recognition site of this transport system. The sequellae of metabolic disorders which can arise following disease or surgical ablation of the ileal region of the intestine which result in an interrupted bile salt enterohepatic circulation are described. We suggest that these findings hold interest to toxicologists, since it is not beyond reason that toxic agents might exist which impair the function of this transport system specifically or which could poison the ileal mucosal cell. Such agents might be detected by the presence of some of the described metabolic disorders. Finally, we discuss the ileal transport of the sulfated esters of bile salts and the possibility that this might relate to that aspect of detoxification pertaining to their enhanced excretion.


A review of the salient features of osteochondrosis in the horse. There appears to be an increasing incidence of osteochondrosis in young fast-growing horses in Europe and the USA. The disease is thought to be congenital in type and affects endochondral ossification in growing bones. It can be localised to one joint or may be a generalised condition. The clinical manifestations of the disease lead to a secondary chronic degenerative joint disease in adult animals. There is a genetic predisposition to the condition which is associated with rapid growth and excessive high energy feeding. The careful genetic selection of bloodstock and restricted intake in early life can greatly assist in decreasing the incidence of the disease.


Bacteria isolated from uterine washings from mares in the Sudan. Uterine washes collected from 200 barren mares were examined at the Khartoum veterinary clinic during the period May 1977 to May 1978. A variety of bacteria was isolated from 77 per cent of the mares investigated. Thirty mares were treated by parenteral injection and intrauterine infusion of the appropriate antibiotics. Twenty-one of these mares conceived, of which 17 delivered normal foals and 4 had early embryonic deaths.


Equine verminous arteritis. An arteriographic evaluation of the larvicidal activity of albendazole. Albendazole was an effective larvicidal anthelmintic against the fourth stage Strongylus vulgaris larvae as late as one month post-infection. The drug was administered at a dose rate of 25 mg/kg three times daily for 5 days. Diarrhoea occurred in 3 of 4 foals treated and of these one died during belated intravenous therapy for dehydration. Arteriography allowed for an in vivo assessment of the development and regression of lesions in infected-treated foals compared to the continued development of lesions in infected-untreated foals. The arteriographic findings were confirmed at necropsy.


A technique for the conduct of nutritional balance experiments in horses. Standardbred geldings were used in a number of nutritional balance experiments. These consisted of 28-day cycles each of an 18-day equilibration period in yards and a 10-day settling  and collection period in metabolism crates. The crates were made of galvanised metal tubing over wooden flooring covered by rubber matting and rubber sheets. Total faeces were collected in trays at the rear of crates and total urine by canvas funnels slung beneath the sheath of each horse.


Tissue and plasma activity of lactic dehydrogenase and creatine kinase in the horse. Lactic dehydrogenase, although widely distributed in most tissues, was more highly concentrated in skeletal muscle, cardiac muscle, kidney and liver. Isoenzyme patterns showed a selective concentration of LDH5 in skeletal muscle while in the heart LDH 1 and 2 were predominant. In contrast, creatine kinase was only present in substantial concentration in skeletal and cardiac muscle. The serum concentrationof both enzymes showed a wide range of activity.


A re-evaluation of the D (+) xylose absorption test in the horse. The absorption of d-xylose forms the basis of a useful screening test in the investigation of small intestinal disorders in the horse. A comparison has been made of different assay methods and there was no significant difference between the results obtained with the parabromoaniline (PBA) method or the ferric chloride-orcinol (FCO) method. The orthotoluidine method was unsatisfactory. The anticoagulant agent did not affect the test. A dose of 0.5 g commercial grade xylose/kg body weight as a 10 per cent solution given by stomach tube, produced a peak plasma xylose level after 90 min and should discriminate normal from abnormal absorption. The FCO method was preferred for the occasional test performed in practice, and a 2-hour sampling period would be adequate.


Assessment of myocardial function in the horse. 2. Experimental findings in resting horses. The paper describes observations on 8 horses at rest using catheter-mounted microtransducers to record intracavity pressures. In 5 of them records were obtained from both left and right sides and in 3 horses from the right heart only. Twelve indices were measured. Variations in left ventricular end-diastolic pressure seemed to influence the results on many of the parameters. It is suggested that left ventricular end-diastolic pressure itself may be a useful guide to left ventricular functional efficiency but more work is necessary to further evaluate these indices as possible measures of myocardial function in the horse.


A survey of early pregnancy losses in West German thoroughbred mares. Embryonic resorption is reported as the main reason for early pregnancy losses in the West German Thoroughbred mare. An analysis of breeding records for the last 11 years showed a resorption rat of 8.4 per cent. Evidence was obtained that these early embryonic losses were associated with too early conception after foaling and with the state of lactation.


A gas chromatographic screening procedure for the detection of non-steroidal anti-inflammatory drugs in horse urine. A gas chromatographic screening procedure for the non-steroidal anti-inflammatory group of drugs is described. The method invovles on-column methylation of the carboxylic acid group using trimethylanilinium hydroxide as the methylating reagent. Fifteen such drugs were studied. Eight of these were detected in urine collected from horses that had received these compounds orally and for these drugs, rates of urinary excretion are recorded. Seven other members of this group of drugs were shown to be detectable by this procedure but in these cases the drug was added to urine and not administered to the horse.


Bridging the gap - some problems of communication and empathy in nutrition education. Among the approaches needed for improving the nutritional status of children, an important one is helping families to develop and use their present resources better. This means, however, bridging the gap in understanding so that feasible advice is given and taken, and mutual trust established between rural people and those who try to serve them. The present paper discusses some of the reasons for this gap and possible ways in which it may be bridged.


Who pays the piper?

Who pays the piper? To what extent have food manufacturers become nutrition educators simply by virtue of the products they advertise, the audiences they address and the intensity of their selling campaigns? Can the food industry do objective nutrition education? Should the food industry be engaged in nutrition education at all? Interest in nutrition education has increased over the last decade, and these questions have become important in both developed and developing countries. The following review attempts to draw some lessons from the United States experience with commercial nutrition education, in the hope that they may prove instructive for nations where food industry educational activities are as yet minimal.


Fish protein concentrate type B - a more promising approach. Dried fish has, from time immemorial, been an important item of the diet. Reduction to a powder for ease of use or storage is only an extension of the process and is by no means a new idea. Intensive efforts have been made in the last twenty years to develop and introduce nutritious low fat, powdered fish products, high in protein and suitable for mass feeding of malnourished populations in the developing world. However, the odourless, low-fat product known as Type A (described in Fd Nutr. Vol. 4, No. 1-2, 1978) failed to attract consumers. Attention is now focussed on Type B, a product containing up to 10 percent fat and tasting and smelling of fish. Its potential as a medium for improving the protein nutrition of vulnerable groups, particularly in developing countries is assessed in this article. Extensive acceptability trials show that up to 35 g per person per week may be included in food-aid programmes among populations accustomed to eating fish. Commercial prospects centre mainly on its use as a food product ingredient.


Nutrition research in the People's Republic of China. According to Mellander (1973), childhood malnutrition has been eliminated in the People's Republic of China, without recourse to international conferences, unusual protein sources, systems analysis, and apparently no applied nutrition programmes. The secret? "A genuine family level approach, providing simple food and simple advise to all families on a basis of absolute administrative priority for prevention in health services and in medical and paramedical education".


Economic importance of breastfeeding.

Economic importance of breastfeeding. While an increasing body of research has documented the importance of breastfeeding for infant health, very little research has been done on its economic implications. From an economic perspective, breast milk can in many respects be regarded like any other food commodity. For example, it could be stored in milk banks, and redistributed from areas of surplus to areas of scarcity. But breast milk is inique in that many of its benefits are associated more with its method of delivery than with its physical or nutritional properties per se. In this study based on field work in West Africa, the authors evaluate the economics of breast-feeding versus artificial feeding, but point out that the major impact of breastfeeding at national level is associated with its health-promoting and birth-spacing effects, neither of which are quantifiable at present.


Malformation of embryonic neural retina elicited by BrdU. Exposure of neural retina tissue from early chick embryos (5 and 6-days) to 5-bromo-2'-deoxyuridine (BrdU) for 24 h irreversibly prevented normal histogenesis and resulted in the formation of chaotically disorganized tissue. The sensitivity of the retina to this effect decreased with embryonic age and declined sharply after the commencement of cell stratification. Examination by electron microscopy revealed the following progressive morphologic changes resulting from BrdU treatment: complete breakdown of the outer limiting membrane due to disappearance of its constituent tight junctions which normally anchor cells at the outer retinal surface; collapse and endocytosis of cilia, resulting in the absence of photoreceptor processes; increasing disorganization of the cells which commenced at the outer surface of the retina and progressed inward, resulting in chaotic distortion of the histologic architecture of the retina. Ultrastructural differences were noted between cells in the malformed retina, indicating the presence of several cell types. Possible mechanisms of this BrdU-elicited malformation are considered in the Discussion.


[Direct cardiac massage in refractory heart arrest. 2 cases sucessfully treated in the coronary care unit]. The open chest, or direct cardiac massage may be indicate in instances where closed chest techniques are ineffective. Direct cardiac massage was successfully applied by us in two patients who failed to resuscitate with closed chest massage. The patients, an 49 year old man with acute myocardial infarction and an 53 year old man who had a history of previous myocardial infarction with subsequent development of a ventricular aneurysm, had ventricular fibrillation who not responded to closed chest cardiac massage and to repeated electrical countershocks. When the pupils became dilated the decision was made to open the chest and apply direct massage. After several minutes of manual cardiac compression a single D.C. countershock returned the heart to a normal sinus rhythm in each of the patients. Although the thoracotomy was performed outside the operating room, none of the complications of the open chest resuscitation occurred, such as intrathoracic infection, rupture of the heart, and postresuscitative bleeding. The first patient recovered from the infarction, has been discharged from the hospital and is alive and well after 5 months. The second patient has been discharged from the U.C.C. and is alive and well after 15 days.


[A new endocardiac electrode for permanent cardiac stimulation]. A modified pacemaker lead has been designed for permanent cardiac pacing. This can be inserted by percutaneous puncture of the subclavian vein using the Seldinger technique. Its use may be advantageous when isolation of an adequate vein for electrode insertion is difficult or impossible.


[Systolic time intervals: echocardiographic study of the right and left ventricle. (author's transl)]. Right and left ventricular systolic time intervals are measured in 40 cardiopathic subjects and compared with the respective values concerning 20 normal subjects. The results show a modification: a) of the values concerning the right ventricle in presence of pathology interesting this ventricle; b) of the values concerning the left ventricle in presence of pathology interesting this ventricle; c) of the values concerning both the ventricles in presence of left ventricular pathology which has, also, interested the right ventricle. The AA. emphasize the importance of the right and left ventricular systolic time intervals not only to separate pathology interesting the right ventricle from that interesting the left ventricle, but also, to evaluate the ventricular performance and the stage of evolution and extension of the cardiopathy.


[Validity of the radiofrequency programmed stimulation in the treatment of the sick sinus syndrome. (author's transl)]. It is presented a patient sick sinus syndrome with the periods of the sinus bradycardia and of the superventricular tachycardia, treated with the implanted of a permanent ventricular inhibited pacemaker  and a passive radio- receiver connected with a ventricular electrocatheter. The tachycardia was interrupted by ventricular way with a discharge of beaths high frequency, utilizing a radiofrequency device connected with a exterior programmed stimulation. It is solicited a more large employment of the radiofrequency stimulation's system in the relapsing and persistent tachycardia, alternately with the pharmacologyc therapy and the DC shock.


[Mitral insufficiency associated with interatrial defect (ostium secundum). Problems of diagnosis and surgical treatment]. Of the 255 patients under observation of the AA. with ostium secundum interatrial defect who underwent surgery, 23 (9%) presented an associated mitral regurgitation. All patients had a hemodynamic test and a complete contrahistography, 8 patients polygraphic and 5 patients echocardiographic examinations. The clinical data alone, ecgraphic and Rx, supplied sufficient indications for a correct diagnosis in 87% of the cases. 22 patients underwent surgery: the septal defect was corrected in all patients, mitral regurgitation only in 9; in 5 by valve substitution, in 4 through conservative techniques. Only one patient died of cerebral coma. A report is made on the data relative to the clinical history, Rx, ecgraphic and hemodynamic examinations of the 23 patients under observation, the various anatomosurgical aspects of the valvular alterations, and the criteria adopted for the surgical correction of the mitral regurgitation.


[Correlations between the patterns--dynamic--of regional contraction and the ECG-enzymatic-clinical signs of myocardial infarction (author's transl)]. 60 patients with clinical signs of coronary artery disease who had a hemodynamic examination were studied. The study of the regional dynamics using the deformation as a vectorial time-dependent parameter and the pressure-length loops, was carried out on a total of 420 parietal regions of the left ventricle: the basal ventriculography, the post-extrasystolic potentiation and the ventriculography after nitroglycerin were evaluated. The dynamic regional pattern was correlated with clinical-enzimatic signs of necrosis in the electrocardiogram. The possibility of correlating signs of necrosis with particular patterns of hypokinesia, akinesia, dyskinesia which differ from corresponding "static" forms of asynergy in active pressure development and deformation (even in a brief systolic interval) seems to confirm the physiopathologic interpretation of the regional phenomenon based on the ratio between viable not viable myocardium -- as primary cause.


[Echocardiography in Ebstein's anomaly (author's transl)]. Results about an echocardiographic study of 20 patients with Ebstein's anomaly diagnosed by cardiac catheterization and angiography, are referred. In 8 patients an echocardiogram and phonocardiogram were recorded and in five patients an echocontrast examination was performed. The echocardiographic features constantly recorded in Ebstein's anomaly are represented by anterior chamber dilatation, interventricular septum paradoxical movement, anterior tricuspid leaflet wide excursion, decreased diastolic closure rate and delayed closure of tricuspid valve compared to mitral valve. The reduced left ventricular dimension and frequent incidence of "hammock-like" shape of mitral valve during systole and reduced diastolic closure rate of anterior mitral leaflet are pointed out. Possible causes of anterior chamber dilatation, of interventricular septum paradoxical motion and delayed tricuspid closure are discussed. According to the previous study no echocardiographic pattern is surely diagnostic of the disease by itself; a delayed tricuspidal closure (more than 70 msec) when associated to an anterior tricuspid leaflet wide excursion and decreased E-F slope, is of particular value for diagnosis.


[Long-term prognosis of survivors from anterior myocardial infarction complicatedy by complete atrio-ventricular block (author's transl)]. Thirteen patients out of 42 affected by acute myocardial infarction complicated by atrio-ventricular block survived the illness and were discharged from hospital. Eight of these patients (60%) died, all in the first six months of follow up: 3 suddenly and 5 in consequence of progressive heart failure. Dead patients were all in III or IV class of the N.Y.H.A. Three had been previously submitted to permanent pacing, one of these died suddenly. Five patients survive at the end of follow up that varies from 2 to 56 months. Of these five survivors 1 patient belong to the I class of the N.Y.H.A., 1 to the II class and 3 to the III class. Among survivors there is only 1 patient with permanent pacing. This is also the only one who had syncopal attacks during a period of pacing failure. Prognosis of patients with myocardial infarction complicated by atrio-ventricular block who survive illness is dependent on functional class and seems to be not considerably modified by permanent pacing.


[The predictability of the degree of right ventricular hypertension after correction of the tetralogy of Fallot]. The validity of an equation which, on the basis of various angiocardiographic measurements allows prediction of the post-repair ratio between the systolic pressures in the right and the left ventricle is retrospectively tested in a series of 46 patients with the "classical" form of tetralogy of Fallot. If the right and left pulmonary arteries are "restrictive", the equation was found to be reliable in such a prediction, provided a negligible gradient is left at the pulmonary anulus level. The implications of the use of this equation on surgical management of patients with tetralogy of Fallot are discussed.


[Digitalis toxicity and digoxin blood levels in children (author's transl)]. Digoxin serum levels in 41 children with clinical and/or ECG symptoms of digitoxicity were determined by radioimmunoassay and compared to the normal values. 54% of the cases showed a good relationship between clinical and/or ECG signs of toxicity and digoxin levels; on the contrary, 29% of patients exhibited only clinical and/or ECG signs of toxicity with normal digoxin levels and 17% of patients had high digoxin levels without signs of toxicity. The significance and possible causes of this relative discrepancy are discussed.


[How much harm can be caused by a badly recorded or badly interpreted ECG! (author's transl)]. Two cases are presented which support the sentence of the title. In a 38 years old man a life insurance company proposed an extra charge on the basis of a pseudoischemic ECG due to exceeding pressure of the writing pen on the ECG paper. In a 28 years old asymptomatic female an abnormal ECG was interpreted as due to ischemic heart disease. Physical activity was restricted and three pregnancies were interrupted. 18 years later an angiography showed normal coronary vessels. Some months later an echocardiogram showed an abnormal pericardial pattern, giving a possible explanation for the abnormal ECG.


[Habitual physical activity and responsibility at work as risk factors of fatal coronary heart disease (author's transl)]. Mortality in 5 and 10 years for all causes in over 172,000 men classified for habitual physical activity at work was not substancially different between subjects classifed as sedentary, moderate and heavy workers. Mortality for coronary heart disease (CHD), for the same length of observation was statistically higher in sedentary and moderate than in heavy workers (ratio 1.7/1). Bivariate analysis considering both physical activity and responsibility at work, limited to 99,000 men aged 40-59 at entry for a period of 5 years having as end-point CHD, indicated that mortality is higher for higher levels of responsability. Partial correlation coefficients between physical activity and working responsibility on one side, and mortality for CHD on the other showed significant levels (-0.72 and 0.71 respectively) when considering eight combination of different activity and responsibility levels.


[Characteristics of drinking water and coronary heart disease. An epidemiological experience (author's transl)]. Mortality for coronary heart disease (CHD) in two samples of men aged 40-59 at entry was rather different after the first 5 year follow-up, but became more and more similar - and substancially identical - after 15 year follow-up. In the community which showed the greatest relative increase of CHD mortality beyond the fifth year, a drastic change in the characteristics of drinking water had occurred, with a large reduction of hardness, and of calcium and magnesium concentration.


[Ergometric evaluation of patients with WPW syndrome (author's transl)]. 20 subjects affected by ventricular pre-excitation, without any other associated cardiac disorder, underwent to maximal exercise test on bicycle ergometer; the aim of the research is to analyse their maximum levels of aerobic power, to study their electrocardiographic behaviour during exercise, with a particular reference to the ventricular repolarization, and finally to evaluate the incidence of arrhythmias during exercise. The maximum aerobic power was slightly lower than the reference standards (on average 78.32%); the muscular work, in 1 patient only, gave rise to cardiac arrhythmias during exercise. In these patients we assume as non specific, the "like ischemic" variations of the ventricular repolarisation during exercise.


[Comparison of the hemodynamic effects induced by dobutamine, isoproterenol and dopamine in patients with coronary artery disease (author's transl)]. The haemodynamic affects of dobutamine (DB) (5 microgram/kg/min), isoproterenol (I) (0.02 microgram/kg/min), dopamine (DP) (5 microgram/kg/min), were studied in 12 patients with coronary artery disease randomly divided in two groups of 6 patients. In one group each patient received DB and I, in the other group each patient received DB and DP. The following parameters were measured: heart rate, aortic blood pressure, left ventricular pressure, left ventricular dp/dt, pulmonary arterial and wedge pressure, cardiac output, stroke volume, peripheral and pulmonary vascular resistances. In both groups either I and DP increased significantly heart rate whereas DB did not modifie it. DB caused a larger increase of dp/dt max and of stroke volume as compared to I and DP. These data confirm that DB possesses an inotropic effect greater than I and DP without any significant positive chronotropic effect in patients with coronary artery disease.


[Post-extrasystolic potentiation for the study of regional left ventricular asynergy (author's transl)]. In 120 P. with ischemic heart disease, left ventricolar wall motion was analyzed from the left ventriculogram in a regular sinus beat as compared to the first beat following one or more premature ventricular contractions (PExP). The response of asynergic segment to PExP was determined with a qualitative as wall as a quantitative technique. Of a total of 225 asynergic segments, 62% showed a positive response to PExP. In the absence of pathologic Q waves in the electrocardiogram, the response was positive in 77% and negative in 23% of the cases. In the presence of Q waves, PExP was present only in 33% of the cases (p less than 0.001). In respect to the severity of asynergy, 68% of 145 hypokinetic segments and 52% of 80 akinetic-dyskinetic segments responded to PExP; in the presence of pathologic Q waves, the number of positive responses decreased to 36% in the case of segmental hypokinesis, and to 31% in the case of more severe asynergy. The study of PExP has appeared as an useful diagnostic technique, capable of detecting a residual myocardial function in left ventricular asynergic segments, even in the presence of electrocardiographic signs of infarction.


[Echocardiographic patterns of congenital aneurysm of the sinus of Valsalva. Review of literature and report of three cases (author's transl)]. The (M-mode) echocardiographic patterns of three patients with congenital aneurysm of the right sinus of Valsalva are reported. In two patients the aneurysm ruptured into the right ventricular cavity. In the third case, in which the lesion was associated with coarctation of the aorta, no communication was shown between the aorta and other cardiac chambers. The characteristic echocardiographic features of the right coronary sinus aneurysm (either with or without rupture in the right ventricular cavity) consist of: 1) The presence of echoes (referable to the right aortic cusp pattern of motion) encroaching the right ventricular outflow tract. 2) The presence of the same box-shaped echoes at a low level of the left ventricular cavity, which seem to "cross" the septum (from the left to the right ventricular outflow tract). These images would reflect the "prolapse" of the affected cusp. Other common, but non-specific echocardiographic features of the lesion are: an indistinct contour of the anterior wall of the aortic root (probably due to dilatation of the right coronary sinus) and systolic indentations on the right anterior aortic cusp echoes.


[Use of the thoraco-acromialis vein for implantation of a permanent transvenous PMK (author's transl)]. In order to implant a permanent PMK in 35 patients with total heart block the thoraco-acromialis vein has been investigated. The vein was easily found in the groove between the clavicular and sternal part of the musculus pectoralis major and used to implant a permanent pacing lead in 32 patients (91.5%). Following the satisfactory results and taking into account that the complications had reduced to a very low rate (in 2 cases lead tip displacement and pouch haematoma occurred respectively), the Authors consider the adopted method an useful approach for PMK implantation particularly when the use of the vena cephalica is deemed impossible.


[The role of the platelets in myocardial infarction induced by isoproterenol in the rat (author's transl)]. The AA. suggest that the myocardial infarction induced by isoproterenol in the rat may be determined by phenomenons of intracoronaric platelets aggregation. The effects on the degree and extension of the infarctual necrotic area have been evaluated in a drug with remarkable platelets antiaggregation activity (ASL). The following parameters are considered: wet and dry weight of the organ, and tissutal CPK levels.


The use of heritabilities of anthropometric measures and performance tests in personnel selection. An analogy exists between the mathematical models of psychological test theory and quantitative genetics. From this analogy we can conclude, that longitudinal correlation and heritability in the broad sense are equivalent expressions for the reliability in the long run. Since long-range prediction is the aim of index construction for personnel selection in athletics and other applied fields, we recommend to use heritability as a weighting factor for phenotypic scores in order to calculate true scores and to eliminate error variance.


[Post-natal growth of the skull in the house mouse Mus musculus Linné, 1758, and in 2 different large subspecies of the field mouse Microtus arvalis Pallas, 1779. II. Results (I)]. Postnatal skull ontogeny of Mus musculus, Microtus arvalis arvalis and M. a. asturianus was studied qualitatively and quantitatively. To facilitate age determination for undated specimens, the most important stages in ossification of the skull bones are described, with drawings of selected ontogenetic stages (Part I). Using Parameter C of the growth function Y(t) = A - B exp (- Ct), it is possible to establish skull growth gradients. The growth functions are subdivided into 3 classes, based on Parameter C, associated with different growth regions of the skull. Changes in individual skull proportions are demonstrated by means of ontogenetic and intraspecific allometries.


[The use of cladistic principles in the phylogeny and biogeography of the Lacerta]. The methodology used in Phylogenetics remains one of the more interesting problems in comparative biology. Among the methods used, the cladistic is the most accurate. In the present case, among the Saurians, the characters chosen appeared early and cannot be referred to any adaptation bound to an evolutive progress. We have successively considered their distribution in the classification, their polarity and one phylogenetic hypothesis based on the Hennig's concepts. Such a work leads necessarily to systematical conclusions. For instance, we note the heterogeneity of some families. Among the Iguania, the Iguanidea are polyphyletics, the north-american forms breaking up from the other very early. Among the Scincomorpha, the Lacertilia result from two parts of different origins. This research verifies some systematic cuttings in the modern classification: among the Anguimorpha, the separation between Helodermatidea and the group, Varanidea-Lanthanotidea. The characters studied show a non-random distribution in the classification and show also some consistency with the geographical distribution of the extant Saurians. Therefore, it is important to search for the most parsimonious geographical hypothesis, which is in concern with the present data on the continental drift and generally on the history of the Earth, and which strengthens the cladograms posed from the selected characters.


Epidemiology and aetiology of aplastic anemia. Epidemiological data show that the incidence of aplastic anemia is a least 4-5 times as high in the far East as in the West. The reason seems to be complex--a number of exogenic factors act against a background of genetic differences in susceptibility. A Swedish study of aplastic anemia shows the overall incidence to be 13 cases per million inhabitants and year, but also that the incidence varies greatly with age (range 4-61 cases per million). Drugs are the single most important aetiologic factor. Chloramphenicol is the most common offender, but in many countries it now has been replaced by the anti-inflammatory agents phenylbutazone and oxyphenbutazone. In Sweden the latter also have disappeared and sulfonamide preparations dominate among drugs causing aplasia.


Co-culture studies in transfused and untransfused patients with aplastic anemia. Co-culture studies have two potential values: (1) In untransfused patients with AA they may be able to detect the small population of patients who have immunologically mediated disease and who therefore may respond to immunosuppressive therapy; (2) In transfused AA patients under consideration for allogenic marrow transplantation, inhibition in the coculture assay may indicate sensitization to minor histocompatibility antigens. Preliminary data indicates that this test may be more sensitive than the chromium release assay and should be added to a battery of prospective in vitro tests designed to detect those patients at risk for marrow graft rejection.


Population and classification of intrapopulation units of helminths. The study of the population problems revealed that the population is an elementary evolution unit of a species with biparental way of reproduction. This is a general theoretical definition which the author elaborated in detail for the helminths. With regard to the complicated intraspecific structure of these parasites also the classification of intrapopulation helminth units is proposed.


The influence of temperature on the development of Moniezia expansa (Rudolphi, 1810) in oribatid mites. The life cycle of Moniezia expansa was studied experimentally using 10 species of oribatid mites as intermediate hosts. Four of them became infected, namely Scheloribates laevigatus (76.2%), Sch. latipes (70.8%), Liacarus coracinus (20%) and Platynothrus peltifer (1.1%). The last was found for the first time to serve as intermediate host of M. expansa in Czechoslovakia. The development of the cysticercoid of M. expansa in the oribatid mites at 28 degrees C and 85% relative humidity is completed within 27 days. At 18-20 degrees C and the same relative humidity the development lasts even 97 days.


Ultrastructure of the cyst of Hymenolepis diminuta larvae. Electron microscopical studies of the cyst of 1-month-old H. diminuta larvae revealed considerable thickening of the superficial syncytium of tegument and formation of a large number of cavities and canals. The cytoplasm of the tegument is filled with microtubules produced by cytons of parenchymal layer which are analogs of tonofibrils. These peculiarities, together with numerous processes of the external fibrous layer, are regarded as adaptative to the changes of the hydrostatic pressure of the hemocoel of the intermediate host. The superficial syncytium is covered with microvilli and keeps polycellular cytoplasmatic bonds with cytons, which ensures energetic and plastic requirements for the stabilization of the hypertrophied syncytium and its physiological regeneration. Accumulations of fibres identical with those of the connective tissue were found in the cytons of the tegument. The cyst parenchyma consists mostly of cells with widened canals of granular endoplasmic reticulum associated with the microfibrils and production of fibrous filaments. The internal fibrous layer is produced by typical fibroblasts. The tegument of the cercomer is thinner and is considered to be less differentiated.


Symptomatology of taeniasis caused by Taenia saginata. The course of an infection with T. saginata has been studied for two years on a volunteer who had swallowed a 16-20 week-old Cysticercus bovis. The pathognomonic character of the infections was shown to be the spontaneous release of cestode proglottids first appearing in the faeces at day 87 p. i. An incidental release of a larger number of segments occurred after an excessive consumption of alcohol. The next release of proglottids followed after 42 to 88 days. The importance of the results of this observation both for the immediate study of the field case and an elucidation of the epidemiology of taeniasis has been evaluated in the present paper.


[Automatic adder mixer for photometric cells: application to superprecipitation of myosin B. (author's transl)]. An automatic adder mixer for  photometric cells was newly developed in our laboratory and was applied in experiments of superprecipitation of myosin B. The mixer has a reciprocating blade-type impeller with a pit for loading samples. The pit was cut so as to be just above the meniscus of the solution in a cell at the top dead point of the cam mechanism and so as to enter the solution at the bottom dead point. When 10 microliter of methylene blue solution was added, the mixing time was 0.6 sec. Myosin B was extracted from rabbit white muscle. Adding ATP (1 mM) to myosin B suspension and mixing was carried out by hand, using a mixing plunger, and also using the automatic adder mixer. The recordings obtained were then compared. Continuous recording of the initial reaction was successfully obtained only when the automatic adder mixer was used. Excellent results were also obtained with respect to reproducibility. The automatic adder mixer is easy to make, inexpensive, and can be utilized in conjunction with conventional spectrophotometers.


[Effect of a non-steroidal anti-inflammatory agent, tolmetin sodium on exudative inflammation in experimental animals (author's transl)]. Effect of tolmetin sodium(Tol) on acute and subacute exudative inflammation was tested in experimental animals. Tol had a potent inhibitory activity (ED50 = 0.75 mg/kg, p.o.) on the increased vascular permeability induced by acetic acid in mice, and the potency was about 0.4 times that of indomethacin (Ind), and 6-93 times that of ibuprofen (Ibu), phenylbutazone(Phe) and aspirin(Asp). The inhibitory activity of Tol(ED50 = 18.2 mg/kg, p.o.) on UV-induced erythema in guinea pigs was about 0.3 times that of Ind. A recovery of the hind paw edema of rats, produced by a mixture of kaolin and carrageenin, was promoted by oral administration of Tol(2.5 approximately 20 mg/kg x 5/2 days). Tol(80 mg/kg/day, p.o.) showed a significant activity in inhibiting the exudation caused by croton oil in rats, and the activity was about 0.025 times that of Ind and greater than that of Ibu, Phe and Asp. Tol(100-800 microgram/ml) inhibited in a dose-dependent manner the phytohemagglutinin-induced blast transformation of cultured lymphocytes from rat thymus, as did salicylic acid. In vitro, Tol showed a potent activity similar to that of Ibu and Phe in preventing the denaturation of bovine serum albumin and the lysis of rat erythrocytes. From these results, it is suggested that Tol has a particularly potent inhibitory activity on acute exudative inflammation, and the mode of action may be attributed to a mechanism similar to that seen with other acidic non-steroidal anti-inflammatory drugs.


[Effects of external Ca2+, dobutamine and other catecholamines on the Ca2+-dependent electrical response (author's transl)]. In isolated guinea pig right papillary muscle, the sodium-carrying system (fast inward current) was inactivated by increasing the external potassium concentration from 5.4 to 16 mM (decrease of an equivalent amount of NaCl). The electrical response was recorded with application of relatively strong cathodal current pulses of 10 or 400 msec duration to the muscle across a partition. The results obtained were; (1) the amplitude of the electrical response increased depending on the strength of the stimulation; (2) the mean rate of rise and the overshoot of this response increased markedly with a high concentration of external calcium; (3) the mean rate of rise (Ca2+ = 7.2 mM; 2.01 V/sec) was considerably smaller than that of the action potential; and (4) this electrical response was not affected by tetrodotoxin (4 x 10(-6) M), but was depressed by Mn2+ (3 x 10(-3) M). These results suggested that the electrical response (slow response) was due to activation of the slow component of inward current, mainly carried by Ca2+. The effect of dobutamine (DOB) on the slow response was studied in vitro, then compared with effects of dopamine (DA), norepinephrine (NE) and isoproterenol (ISO). These catecholamines (CA) increased the amplitude of the slow response and the sensitivity to electrical stimulus strength. Augmentative effects of these drugs were in the following order of ISO greater than NE greater than DOB greater than DA. The finding that DA and ISO increase the sensitivity to electrical stimulus strength more than the amplitude of slow response will be researched in further investigations.


[Effects of adenosine triphosphate on the postrotatory nystagmus and disorders of vestibular function (author's transl)]. Effects of adenosine triphosphate (ATP) on the postrotatory-induced nystagmus in rabbits and disorders of vestibular function induced by repeated administration of streptomycin in guinea pigs were studied. ATP-2Na exerted little influence on the postrotatory nystagmus in doses of 3 and 10 mg/kg, i.v., while slight suppressive effects were noted with a dose of 30 mg/kg. On the other hand, diphenidol hydrochloride remarkably suppressed the postrotatory nystagmus in a dose of 3 mg/kg i.v.. The disturbance in vestibular function following administration of streptomycin sulfate (400 mg/kg i.m., once daily x 9) was significantly alleviated when concomitant treatment with ATP-2Na (3 mg/kg i.p., 10 mg/kg i.p. and 100 mg/kg p.o., once daily x 14) or diphenidol hydrochloride (50 mg/kg p.o., once daily x 14) was given. ATP as well as diphenidol alleviated disorders in the vestibular function, while ATP had little influence on vestibular function in intact animals.


[Effect of 1-[(1-pyrrolidynylcarbonyl) methyl]-4-(3, 4, 5-trimethoxycinnamoyl)piperazine maleate (cinepazide) on cerebral and peripheral circulation in cats (author's transl)]. Effects of cinepazide, a vasoactive agent, on regional circulations in various sites of brain and other organs in curarized, artificially respirated cats were studied using a thermoelectrical method. The mechanism of the vascular effect was also investigated. Cinepazide produced a marked increase in blood flow in the cerebellar cortex and an apparent increase in blood flow in the cerebral cortex. Effects of the drug on blood flow in the thalamus, hypothalamus and amygdala were inconsistent. Cinepazide produced the most significant increase in myocardial blood flow and also an apparent increase in muscular blood flow, whereas the drug did not consistently alter hepatic blood flow, and decreased renal and dermal blood flow. Cinepazide produced a mild and sustained fall in blood pressure, however, a transient slight rise in blood pressure was noted when the drug was given into the vertebral artery. It seems possible that the action of cinepazide might involve a mild stimulation of beta adrenergic receptors and slight stimulation of alpha adrenergic receptors but not cholinergic receptors, in the cerebral and peripheral vascular systems. Increase in blood flow induced by cinepazide seems to be mainly due to the smooth muscle relaxant effect and may be mediated via a metabolic mechanism.


[Cardiovascular pharmacology of cinepazide, a new cerebral vasodilator (author's transl)]. Cardiovascular effects of cinepazide were compared with those of cinnarizine and papaverine. Cinepazide (3-30 mg/kg, i.v.) produced a dose-related and transient increase in vertebral, carotid, renal and femoral arterial flow as well as cardiac output and a decrease in total peripheral resistance in anesthetized dogs. The magnitude and duration of mesenteric vasodilatation induced by cinepazide was much greater as compared to other vascular effects, and these effects were associated with a prolonged hypotension. The drug exerted positive inotropic and chronotropic actions, the latter being followed by bradycardia with the highest dose. Cinnarizine (0.3-3 mg/kg, i.v.) produced a greater increase in vertebral blood flow with bradycardia and papaverine (0.1-1 mg/kg, i.v.) produced a remarkable carotid vasodilatation with cardiac stimulation. Both reference drugs decreased renal blood flow. Cinepazide (30 mg/kg, i.v.) potentiated the vertebral vasodilator response of dogs to intravertebral adenosine and cyclic AMP, while cinnarizine (3 mg/kg i.v.) reduced their vasodilator effects. Intravertebral cinepazide(1-10 mg), like cinnarizine (0.1-1 mg) and papaverine (0.1-1 mg), increased vertebral blood flow in a dose-related manner and the effect was partially inhibited by intravenous pretreatment with aminophylline but not by pretreatment with autonomic antagonists. These antagonists did not modify the cinnarizine effect. Cinepazide resembled cinnarizine and papaverine in that the drug antagonized rabbit aortic contraction induced by KCl, norepinephrine or CaCl2.


[Effects of diazepam and baclofen on the anemic decerebrate rigidity in rats (author's transl)]. Effects of diazepam and baclofen on the anemic decerebrate rigidity in rats were studied by using the drugs that modify GABAergic mechanisms of deplete catecholamine. Rigid forelimb tension in anemic decerebrate rats took the form of tonically sustained tension (tonic component), while the phasic tension (phasic component) was induced by mechanical stimulation of hindlimbs. Diazepam exerted a marked dose-dependent inhibition of the phasic component, whereas baclofen produced a similar effect on both tonic and phasic components. In rats pretreated with semicarbazide, the inhibitory effect of diazepam on phasic component was reduced, and the effect of semicarbazide was antagonized by pyridoxine. The effect of diazepam was slightly enhanced by pretreatment with aminooxyacetic acid, and antagonized by picrotoxin. In contrast to diazepam, the depressant actions of baclofen on both components were not affected by semicarbazide, aminooxyacetic acid or picrotoxin. Catecholamine depletion produced by alpha-methyltyrosine or disulfiram significantly reduced the effect of baclofen on the phasic component. It thus appears that GABA is involved in the effect of diazepam on the phasic component, and noradrenaline is involved in the same effect of baclofen in anemic decerebrate rats.


[Drug interaction on antitumor drugs I. Antitumor activity of cyclophosphamide in mice consecutively administered aminopyrine, chlorpromazine, or morphine (author's transl)]. Antitumor activity and lethality of cyclophosphamide alone and in combination with several drugs were investigated in male ddY mice. The antitumor activity was estimated by weighing the solid tumor on the 15th day after Ehrlich ascites cell inoculation. Pentobarbital induced sleeping time for monitoring the activity of hepatic drug-metabolizing enzymes was defined as the time between the loss and the recovery of the righting reflex. Consecutive administration of pentobarbital shortened the pentobarbital sleeping time and increased the antitumor activity after cyclophosphamide. On the contrary, a single administration of SKF 525A or cycloheximide prolonged the pentobarbital sleeping time significantly and decreased the antitumor activity after cyclophosphamide. Consecutive administration of aminopyrine, or chlorpromazine shortened the pentobarbital sleeping time and increased the antitumor activity after cyclophosphamide. These results indicate that aminopyrine and chlorpromazine may increase the levels of the hepatic drug-metabolizing components and may activate cyclophosphamide by conversion to an active form. Effect of a consecutive administration of morphine on the pentobarbital sleeping time and the antitumor activity was uncertain in individual cases. On the other hand, aminopyrine, chlorpromazine, or morphine in consecutive administration increased the lethality of cyclophosphamide.


[Effects of thiol compounds on experimental liver damage (II). Preventive and therapeutic effects of tiopronin (2-mercaptopropionylglycine) and glutathione on ethionine induced liver damage (author's transl)]. Preventive and therapeutic effects of tiopronin (2-mercaptopropionylglycine) and glutathione on ethionine induced liver damage were studied. Administration of 1 g/kg ethionine resulted in significant differences in the degree of liver damage, and such was dependent on the feeding conditions of the animals. The present experiment was performed under the conditions where the most serious liver damage was observed. In the experiment on the preventive effects, serum GOT and GPT were markedly elevated by ethionine, but such elevation could be suppressed by administering tiopronin or glutathione 10 min before ethionine administration. Liver nonprotein thiol (NPSH) content decreased by 40--60% of the normal level 16 hr after ethionine adminstration, but increased by 30--45% 24 hr later. Administration of tiopronin suppressed the initial fall of liver NPSH content caused by ethionine, but this tendency was not observed in the glutathione treatment. Both liver cholesterol and triglyceride increased in the ethionine treated rats, and triglycerides in particular decreased with administration of tiopronin or glutathione. In the experiment on the therapeutic effects, the maximal values of serum GOT and GPT brought by ethionine were suppressed by the thiol compounds given 16 hr after ethionine administration, but liver NPSH content and liver lipids were not influenced. Thus, tiopronin and glutathione are considered to have preventive and therapeutic effects on liver damage induced by ethionine.


[Behavioral and EEG effects of Zingiber mioga Roscoe (water soluble fraction) (author's transl)]. Behavioral and EEG effects of water soluble fraction extracted from Zingiber mioga Roscoe (Z. mioga) were investigated in mice, rats and rabbits. Z. mioga was dissolved in isotonic saline and given i.p. into mice and rats, and i.v. into rabbits, respectively. Z. mioga at doses of 50 approximately 400 mg/kf produced a marked reduction in locomotor activity of mice in the open-field test. The peak time of reduction was 30 min after the injection. In mice, Z. mioga at the same doses lowered significantly the rectal temperature and prolonged the sleeping time induced by thiopental-Na (40 mg/kg, i.v.). Z. mioga at a dose of 400 mg/kg had no anticonvulsant effects and it produced a slight muscle relaxation in mice. Z. mioga at doses of 50 approximately 200 mg/kg induced a significant inhibition of the active conditioned avoidance response of the rat in a shuttle box without affecting the unconditioned escape response. In the step-down method, however, the passive conditioned avoidance response was rarely affected by Z. mioga, but the response was suppressed by chlorpromazine. In rabbits with chronically implanted electrodes, Z. mioga at doses of 20--30 mg/kg induced a drowsy pattern of spontaneous EEG, ilel high voltage slow waves in the neocortex and amygdala, and desynchronization in the case of hippocampal theta waves. The EEG arousal response to the external auditory stimulation was inhibited by the same doses of Z. mioga, whereas it failed to suppress the arousal response to either the midbrain reticular or posterior hypothalamic stimulation, as with chlorpromazine. Neither the recruiting response nor the photic driving response were affected by Z. mioga. On the other hand, the limbic after-discharges to the hippocampal or amygdaloid stimulation were enhanced by Z. mioga as well as chlorpromazin, but they were inhibited by diazepam. The EEG effects of Z. mioga were qualitatively similar to chlorpromazine, but not to diazepam. These results indicate the similarity of behavioral and EEG effects of Z. mioga to those seen with neuroleptics such as chlorpromazine.


[Studies on biopharmacological actitivy of active vitamin D3 analogues (VII)  Effect of 1 alpha-hydroxycholecalciferol on renal function in rats and Beagle dogs (author's transl]. In male Wistar rats, 1 alpha-HCC and 1 alpha, 25-DHCC induced diuretic effects in doses of 2.5 and 25 micrograms/kg p.o., while no such effects of 1 alpha-HCC were seen with a dose of 0.25 microgram/kg p.o. Effect of 1 alpha-HCC appeared later than that of 1 alpha, 25-DHCC, but at 24 hr, the difference disappeared. Similar results were obtained with urinary concentrations of calcium (increase) and phosphorus (decrease). Glomerular filtration rate (GFR) and tubular reabsorption of phosphate (TRP) were remarkably elevated by 1 alpha, 25-DHCC, and effects of 1 alpha-HCC were rather weak and apparently not dose dependent. In light of these results and the finding that there was no difference between the effects of 1 alpha-HCC and 1 alpha, 25-DHCC on serum calcium and phosphorus at 24 hr, the mechanism of action of these sterols on the renal function seems to differ. In male Beagle dogs, 0.25 microgram/kg/day p.o. of 1 alpha-HCC or 1 alpha, 25-DHCC induced a severe hypercalcemia and GFR was decreased in the 1 alpha, 25-DHCC treated group. A gradual recovery occurred with cessation of the administration. Thus decrease in GFR was considered to be due to calcification of the kidney.


[Effect of thiol compounds on experimental liver damage (IV). Detoxicating effect of tiopronin, glutathione and cysteine on ethionine induced lived damage (author's transl)]. S-GPT elevated due to ethionine (Eth) administration was suppressed by thiol compounds such as tiopronin (2-mercaptopropionylglycine), glutathione, cysteine, in which tiopronin proved to be more effective than glutathione or cysteine. In thin-layer chromatography of urinary metabolites, Eth and ethionine sulfoxide were detected with administration of Eth, and S-ethyltiopronin plus Eth and ethionine sulfoxide by the administrations of Eth and tiopronin. These S-ethyl derivatives were not detected in the urine with administration of Eth and glutathione or cysteine. In the analysis of Eth and its metabolites by gas chromatography, cumulative urinary excretion of Eth within 72 hr after Eth administration was 40.7% in the Eth administered group, 23.6% in the Eth-tiopronin administered group and 38.2% in the Eth-glutathione administered group, respectively. In the urine of the Eth-tiopronin administered group, S-ethyltiopronin was excreted by 13.6%. Detoxicating effect of tiopronin on Eth induced liver damage was considered to involve the following mechanism. Tiopronin is considered to excrete part of Eth as S-ethyltiopronin by being an acceptor of transfer reaction of the ethyl group of Eth. Neither glutathione nor cysteine was an acceptor of the ethyl group and a detoxicating effect on Eth was not observed.


[Pharmacological studies on Zingiber mioga (ZM) (1). General pharmacological effects of water extracts (author's transl)]. In the central nervous system, ZM decreased locomotor activity and potentiated hypnosis of hexobarbital-Na in mice. ZM had little hypothermic action and there were no anticonvulsive effects on chemoconvulsion and electroconvulsion shock. ZM, 3 mg/kg i.v. produced a sleep-like pattern in the spontaneous EEG activity of cat; from 20 to 30 min. after injection, spindle burst-like waves (12-13 Hz) appeared in the cortex and subcortex. These EEG activities were antagonized by atropine sulfate. In the respiratory and cardiovascular system, ZM, 1 mg/kg or over produced a fall in blood pressure and stimulated respiration in dogs. This hypotensive action was antagonized by atropine sulfate and diphenhydramine hydrochloride, and tachyphylaxis was observed in blood pressure. This compound inhibited cardiomotility in isolated toad heart, had little effect on peripheral blood flow, and produced contractions of isolated guinea pig ileum which were inhibited by atropine by sulfate. Regarding inflammatory response, ZM showed inhibitory effects on the acute edema induced serotonin and dextran. These results indicate that water extracts of ZM have cholinergic actions and in peripheral tissues, histaminergic-like actions.


[Individual differences in the accelerating effect of methamphetamine, d-amphetamine and morphine on ambulatory activity in mice (author's transl)]. Several problems concerning the ambulatory activity were discussed from the viewpoint of drug assay using about 700 adult male mice of ddG strain. Each response pattern for 180 approximately 400 min obtained from the temporal changes of ambulatory activity after administration of methamphetamine (1 approximately 16 mg/kg s.c.), d-amphetamine (1.25 approximately 5 mg/kg s.c.) or morphine (5 approximately 20 mg/kg s.c.) was recorded and used for the data analysis. All the above mentioned drugs markedly accelerated the activity when the doses were optimal. However, the individual response to the drugs sometimes reached a 40- approximately 70-fold difference, even though both animal and measurement conditions were fixed as constant way as possible. The time when the experiments took place did not explain the individual differences, nor did the season or body weight of the animal. However, there was the possibility of colony differences. Animals with relatively high activity prior to drug administration tended to respond more forcibly after administration of the drugs. It was found from the statistical investigation that constant observation of over 1 hr using at least 15 animals was required in order to determine a standard effect of the drug. Furthermore, the accelerating effect of methamphetamine and d-amphetamine on the activity was observed to be dose-dependent when below 4 and 5 mg/kg was given, respectively. On the contrary, the effect decreased dose-dependently when higher doses were given as stereotyped behavior such as head-swaying, continuous sniffing and circular movements in opposition to the horizontal movements also developed dose-dependently. As the qualitatively different behavior could be simultaneously measured, the individual differences were more apparent.


[Pharmacological studies on Zingiber Mioga (2). Effects of water extracts on the central nervous system (author's transl)]. Effects on the cat central nervous system of water extracts of Zingiber Mioga (ZM) were studied by electroencephalography (EEG). ZM had little effect on the EEG arousal response to electrical stimulation of mid-brain reticular formation. ZM (3 approximately 5 mg/kg, i.v.) suppressed the recruiting response and the augmenting response recorded from the posterior sigmoid gyrus, respectively. ZM (1 approximately 3 mg/kg, i.v.) decreased the photic driving response, while 5 mg/kg, i.v., tended to enhance the response. In the chronic experiments, ZM(1 approximately 3 mg/kg, i.v.) induced a drowsy pattern in the cortex and subcortex, and shortened the lasting time of the EEG arousal response to sonic stimulation. After 5 to 10 minutes, behavior showed a drowsy to light sleeping state, and electromyogram recorded from the platysma showed a decreased amplitude and frequency, but, did not have an inhibitory effect on the motor system, (ataxia). ZM (5 mg/kg, i.v.) induced desynchronization in the cortex and subcortex, arousal wave appeared in hippocampus, midbrain reticular formation, nucl. ventralis postero-lateralis and amygdala, and behavior tended toward the awake stage. After 10 minutes, EEG transferred to a drowsy pattern and behavior showed a drowsy to light sleeping state. The animal could be readily awakened by sonic stimulation, at every time. ZM appears to have an inhibitory effect on the central nervous system.


Systematic relationships of gorillas from Kahuzi Tshiaberimu and Kayonza. Previous classifications of gorillas from Mt. Kahuzi, Mt. Tshiaberimu and the Kayonza Forest, placing them in Gorilla gorilla graueri or G.g. beringei, somewhat over-simplify a complex situation. Both Kahuzi and Tshiaberimu gorillas are close to graueri and should be placed in that subspecies, but each (in different ways) shows some approach to beringei, either through independent adaptation to extreme montane conditions, or because they may be points along a (now disrupted) cline from one race to the other. A hypothesis for the dispersal of beringei is presented, making use of geophysical data on the movement of the African plate over the Virunga 'hot-spot'.


The external nose of Tarsius bancanus borneanus Horsfield, 1821 (Primates, Tarsiiformes). A gross anatomical and microscopical study of the external nose of Tarsius bancanus borneanus demonstrated the typical strepsirrhine shape of the nostrils and an extreme platyrrhine condition. The wide internarial area possesses no sinus hairs. The concepts of strepsirrhinism and haplorrhinism may be used to characterize the different shapes of the nostrils, but they do not have any taxonomical significance.


[Congenital diaphragmatic eventration].

[Congenital diaphragmatic eventration]. The nomenclature of congenital defects of the diaphragm is not unequivocal. Congenital eventration means the incomplete ingrowth of muscle fibers between the pleural and peritoneal sheet of the diaphragm during the embryonal period. The differential diagnosis of eventration and hernia may be very difficult. The adequate surgical treatment differs. As concomitant congenital defects of the ipsilateral lung often occur, congenital eventration should be operated by transthoracic approach. The prognosis of symptomatic eventration is poor in newborns and good in adults. This is illustrated by two own cases. The one deals with a newborn who had a large congenital eventration of the left diaphragm; the other has been reported detailed elsewhere.


[Side effects of whooping cough inoculation]. During 1970 to 1977 adverse reactions after pertussis vaccination were reported for 149 children, 56% male and 44% female. Their symptoms permitted to divide the vaccinees into 2 groups: one with more severe (S) and the second with other symptoms (0). No differences were observed in age and sex among the two groups. The interval between vaccination and appearance of first symptoms was longer for the 0 than for the S group. While less than one quarter of the reactions in the 0 group occurred after primovaccination, more than half of the S side effects were seen after the first vaccination. Further analysis of the S group revealed, that all but two of their symptoms (fever and encephalopathy) corresponded to the hypoglycaemic syndrome. The consequences hereof are discussed with regard to prevention and therapy.


[Results of an altered resection in the Billroth II-resected stomach for restoration of the gastroduodenal passage]. Our indications for re-establishment of the gastroduodenal passage were complicated and intractable anastomotic ulcers (20 patients), loop- (8 patients) and dumping-syndromes (8 patients). All 36 procedures were carried out without mortality. Two additional reoperations were necessary because of one anastomotic stenosis and one recurrent ulcer. 83% (24 out of 29) of the patients, who had follow-up examinations, were free of complaints. Normalization of resorptive function by re-establishment of gastroduodenal passage could be proven objectively by normal laboratory values and an increase in body weight.


[Intelligence testing in early old age. The correlation between the multiple-choice vocabulary test (MCVT-B) and the progressive matrices test (PMT) in a patient cohort in early old age]. Taking a random sample of 147 patients a substantial correlation of 0.54 between the "Mehrfachwahl-Wortschatz-Test (MWT-B)" by Lehrl and the "Progressiver Matrizen-Test" by Raven could be found. The MWT-B did not show significant differences between the age groups of 34-44 years, 45-54 years and 55-64 years. In the PMT differences between the age groups only showed up when the raw-scores were converted to IQ-scores (reffering to the corresponding age groups). Using the raw-scores no significant differences could be determined. Investigating an average IQ of 109 in the PMT, we found an average IQ of 97 in the MWT-B for the same patients. A main reason for the superelevated IQ-scores in PMT seems to be the reference to different age groups. A new standardization of the test should be undertaken.


Corneal endothelium: a modified method for cultivation. A modified method for establishing cultures of rabbit corneal cells is described. The new technique utilized a Lucite disc in combination with a Tygon ring for growth of pure cell cultures and was compared with an explant method for growing cells. Each method provided adequate cell cultures for biochemical or ultrastructure studies of rabbit corneal cells, but the ring and disc method described here allowed the isolation of specific cell types without the interference of stromal cell contamination.


Conditions affecting prolonged maintenance of mouse and rat colon in organ culture. The effect of variations in culture conditions on survival of fragments of mouse and rat descending colon in organ culture was studied by morphological and functional criteria. A combination of conditions demonstrated to be beneficial permitted maintenance for at least 35 days. These included: a gaseous environment of 95% O2:5% CO2, an attachment matrix consisting of a Metricel GA-4 membrane (pore size, 0.8 mu), intermittent exposure to the gas and fluid phases by rocking in 5 ml medium and supplementation of the medium with 1.0 microM dexamethasone and 10% FBS. During this time, the crypt structure of the mucosal epithelium was well preserved, and DNA synthesis in the crypts and mucin production in the crypts and superficial epithelium continued. In addition, the synthetic trophic hormone, pentagastrin, stimulated DNA synthesis in the mucosal epithelium of mouse colon fragment in short-term organ culture.


Lactogenic response of mouse mammary explants from different days of pregnancy to placental lactogen and pituitary prolactin. The lactogenic response of mouse mammary gland explants to human placental lactogen (hPL) and ovine pituitary prolactin (oPRL) was examined on days 10 to 18 of pregnancy by measuring 3H-amino acid incorporation into calcium-rennin precipitable casein. To determine the lactogenic response of the explants, the mean slopes of dose-response curves were calculated for each hormone treatment. Slope means of dose-response curves for oPRL and hPL did not differ from each other on any day of pregnancy examined. A triphasic pattern of response was suggested when slope means of dose-response curves for both hormones were plotted as a function of day of gestation. Peak responses were observed on days 10, 13 and 17-18. Combinations of oPRL and hPL, in ratios of oPRL:hPL = 2:1 and oPRL:hPL = 1:2, also produced a triphasic pattern of sensitivity very similar to that produced by either hormone alone. These results suggest that mouse mammary explants may be more sensitive to oPRL and hPL on days 10, 13 and 17-18 of pregnancy.


Effect of different fetal bovine serum concentrations on the replicative life span of cultured chick cells. The effect of Eagle's minimal essential medium, containing different fetal bovine serum (FBS) concentrations, on the proliferation and replicative life span of cultured chick cells has been studied. Our results showed that the rate of chick cell proliferation and the cell density at stationary phase increased as a function of serum concentration between 5 and 30% FBS. The replicative life span of cultured chick cells was dependent on the FBS concentration between 5 and 20% in a medium volume of 0.20 ml/cm2. The maximum replicative life span of chick cells was obtained by serially propagating cells in a medium volume of 0.20 ml/cm2 containing 20 or 30% FBS, or, alternatively, in 0.53 ml/cm2 containing 10, 20 or 30% FBS. Cells grown in medium containing 5% serum had a calendar life span of 35 days, whereas cells propagated in medium containing higher serum concentrations had a calendar life span of 50 days. These results reenforce the concept that, although the kinetics of cell population aging can be affected by the culture medium composition, the aging of cells in culture is controlled by alterations within the cell.


Establishment of epithelial cell lines from adult mouse regenerating liver. A simple technique for developing epithelial cell lines from regenerating mouse liver has been described. Twenty-one epithelial cell lines have been developed and can be divided into four groups according to their morphology. All these near diploid cell lines have the capacity to metabolize diverse classes of chemical carcinogens (3-methylcholanthrene, 2-acetylaminofluorene, dimethylnitrosamine and aflatoxin B1) to cytotoxic metabolites. It is not yet possible to determine which ones of these cell lines originated from hepatocytes. Studies are in progress to further characterize and to use these cell lines as lethally irradiated feeder layers for cell-mediated activation of various classes of chemical carcinogens and mutagens with C3H/10T1/2 mouse embryo fibroblasts as indicator cells.


Injury to primary cultures of rat heart endothelial cells by hypoxia and glucose deprivation. Primary cultures of rat heart endothelial cells were subjected to simulated conditions of ischemia: hyposia and glucose deprivation for 4 and 24 hr. Cellular injury was evaluated by measuring changes in viability, total protein, cellular morphology, and leakage of cytoplasmic enzymes from the cells into the culture medium. Deprivation of oxygen and glucose for 4 or 24 hr did not lethally injure the cells as noted by no change in cell viability, morphology, and total protein when compared to controls. However, reversible or non-lethal cellular injury was produced as reflected by a significant release of lactate dehydrogenase (LDH) from the cells into the medium after treatment with hypoxia and glucose deprivation for 4 or 24 hr. When the cultures were deprived of glucose, but were oxygenated, cellular injury was not evident after 24 hr. Deprivation of oxygen but not glucose resulted in significant loss of LDH after 4 or 24 hr. When the cultures were allowed to recover after oxygen and glucose deprivation in complete medium containing 1000 mg glucose per 1 and a normal atmosphere of 20% O2, they had levels of LDH leakage comparable to those of control cultures.


A syngeneic anti tumor serum recognizing a complex H-2 alloantigen. A methylcholanthrene induced tumor of BALBc (H-2d) origin had a high rate of spontaneous regression when transplanted into syngeneic animals. The tumor induced in BALB/c mice iso-antibodies with high anti-tumor cytotoxic activity. A specificity analysis of such BALB/c anti MCG4 sera revealed that the antibodies were directed against a tumor antigen which is very similar to H-2- alloantigens (e.g. H-2.5) expressed on normal cells of certain foreign mouse strains. The sera also reacted with nine out of ten B10.W congenic strains bearing H-2wi haplotypes derived from wild mice. Whether the tumor antigen is identical with foreign H-2 antigens or only cross-reactive cannot be decided at present.


Isolation of late complement components by affinity chromatography. II. Purification of the human complement component C6. We developed a new procedure for the rapid and gentle isolation of the human complement component C6 comparable to that described previously for C9. The procedure is based on affinity chromatography. As a first step, C6 is immunoabsorbed on insolubilized anti-C6 antibodies. These antibodies were derived from C6-defective rabbits (Freiburg strain). C6 was eluted with 3 M thiocyanate, pH 7.2, with a recovery of 15--23% of its hemolytic activity and a more than 270--fold purification. Impurities were removed in a second step by an "anti-impurity" column. The final product yielded a 12% recovery of the hemolytic activity and the purification factor was higher than 1300. The final product was homogeneous in SDS polyacrylamide and immunoelectrophoresis.


Precipitating and non-precipitating complement consuming IgG subclass antibodies in pigeon breeders' disease. The sera of patients with pigeon breeder's disease usually contain precipitating serum factors as well as human complement consuming factors as shown by incubation of the serum with pigeon dropping antigens. Although a single serum factor, possibly an IgG antibody, might account for both phenomena, affinity chromatography experiments revealed that the sera of patients with pigeon breeders' disease contain non-recipitating, human complement consuming, serum factors besides precipitating serum factors which are also capable of complement consumption. The non-precipitating serum factors most likely belong to the IgG3 immunoglobulin subclass, whereas the precipitating antibodies belong to the subclasses IgG1 and IgG2.


Cation requirement of natural, in-vitro generated and antibody dependent killing exerted by human lymphocytes. Three cytotoxic systems, NK, ADCC and the seemingly indiscriminative cytotoxicity of in vitro activated lymphocytes (cultivated with K 562) were found to require Ca++ and did not function in Mg++. The optimum concentration of Ca++ was identical for the three systems and for various lymphocyte subsets. 15 minutes after initiation of the interaction cell damage had already occurred in all three systems.


Correlation between effector lymphocytes in natural and antibody-mediated cytotoxicity. Human sera enhanced spontaneous cell-mediated cytotoxicity (SCMC), while anti-IgG (Fab') 2 treatment decreased this cytotoxic activity of human lymphocytes for an in vitro growing cell line (K--562). Trypsin treatment of the effector cells considerably decreased the cytotoxic potential. However, a significant cytotoxic activity could always be found in serum-free medium. While these findings suggest the involvement of antibodies in the SCMC, they also reflect the existence of serum-indpendent (sui generis) SCMC activity of lymphocytes. Removal of SCMC of Fc receptor bearing effector cells was performed by target cell adherence (rosetting). Separation of the target cell-bound lymphocytes was done by centrifugation on special Ficoll gradient. The depletion of SCMC effector cells resulted in a 62% reduction of SCMC and in a 39% reduction of ADCC. On the other hand, removal of Fc bearing effector cells showed a similar reduction in both ADCC (66%) and SCMC (78%). Our results suggest that SCMC represents a complex activity, arising partly from the interactions of certain serum-derived or lymphocytes surface-bound antibodies and partly from a spontaneous cytotoxic function of the effector cells. It is possible that the effector cells involved in both SCMC and ADCC derive from the same lymphocyte population and the differences are due mainly to the lower number of SCMC effector cells.


[Serological classification of post-transfusion hepatitis (author's transl)]. Post-transfusion hepatitis (PTH) remains to be a major hazard after massive blood transfusions. After 141 cardiac surgeries with massive blood transfusions the frequency of PTH reached 38%. The natural history of this type of hepatitis proved to be clinically mild but usually protracted. Icterus was found in one third. Serologically 46% of the PTH could be identified by HBs-Ag-testing as type B hepatitis. 39% revealed anti-HBs and 15% remained unclassified. HBs-Ag or anti-HBs were found in 40% patients without clinical or biochemical evidences of a hepatitis. The diagnosis of PTH still should rely on a synopsis of a typical clinical and biochemical hepatitis syndrome, characteristic serological findings and an adequate intervall between blood transfusion and outbreak of hepatitis.