A pharmacokinetic model for predicting pesticide residues in fish.

By using the compartmental analysis approach of pharmacokinetics, found useful in describing the kinetics of a foreign compound in a biological system, a rather simple mathematical model was developed to predict, by computer simulation, steady-state pesticide residues in fish from limited pre-steady-state experimental data. Such steady-state data are needed in order to calculate the tendency of the residue to concentrate in fish--the so-called bioconcentration factor. The model was applied to four different carbon-14 labeled biocides at seven concentrations. Considering the simplicity of the model and the fact that residues were measured by the non-specific technique of radioassay, model predicted values were in good agreement with experimental values.


Inhibitory effect of cadmium on calcium absorption from the rat duodenum.

Male rats of the Wistar strain (6 weeks old) were divided into 2 groups; control group and experimental group. The control group was fed a cadmium-free diet. The experimental group was fed a diet containing 100 ppm of cadmium (CdCl2). During the 33-day period of cadmium intake, body weight was recorded. For the 7th to 10th, 16th to 19th, and 25th to 28th day of the experimental period, food consumption was recorded and at the same time urine and feces were sampled to obtain the calcium and phosphorus concentrations. On the 8th, 17th, and 26th day, about 0.2 ml of blood was sampled to determine the calcium and phosphorus concentration. The concentration of calcium remained stationary during the experimental period, but the concentration of phosphorus in the experimental group was significantly lower than that in the control group. On the 29th or 30th day 45Ca(1 muCi) was given orally with the cold calcium, and the 1- and 2-hr blood was collected by heart puncture to obtain the 45Ca activity in the serum. The 1-hr activity in the control group was significantly higher than that in the experimental group. On the final day, the rats were sacrificed to obtain the duodenum and kidney calcium-binding protein. The binding activities of these proteins in the experimental group were significantly lower than that in the control group.


Biological activity of insect juvenile hormone analogues against the stable fly and toxicity studies in domestic animals.

The insect JHAs are effective inhibitors of adult stable fly development. Laboratory and field evaluation studies demonstrated that area application of the analogues to larval breeding sites was efficacious for stable fly control in cattle feed lots and in marine grasses. Analytical methods by quantification with gas chromatography with flame ionization detection was developed to measure residual properties as well as aging and leaching in fly breeding media. The analogues did not interfere with the oviposition and development of the endoparasites, M. raptor and S. endius. Toxicity studies against swine, hamsters, and sheep showed that when compounds of high purity were used that no toxic effects were observed in any of the species.


Effects of weathering and flue-curing on methomyl residues on tobacco.

A replicated field experiment was conducted at two locations to determine the disappearance of methomyl from flue-cured tobacco. Immediately after application, methomyl residues were 88 and 113 ppm at Clayton and 44 and 105 ppm at Reidsville, respectively, for 0.56 and 1.12 kg/ha application rates. After 5 days these levels dropped to 0.7 and 2.8 ppm at Clayton and 1.4 and 4.1 ppm at Reidsville. At 9 days after application, 99% of the methomyl had disappeared at both locations. Losses of methomyl during flue-curing averaged 96% over locations, rates of application, and times of harvest, compared to an average loss of 98% due to weathering in the field for 5 days. The disappearance of methomyl during the curing process was approximately the same for both locations.


Trace metal concentrations and partitioning in zooplankton, neuston, and benthos from the south Texas outer continental shelf.

A variety of marine biota, including zooplankton, sargassum, surface plankton, squid, shrimp, and fish collected along the south Texas Outer Continental Shelf, were analyzed for Cu, Zn, Cd, Pb, Cr, Ni, Fe, and Mn. Although there is a great deal of variation in the chemical content of the various samples, both within species and between species, the variations all fall within the range of values published for similar organisms collected elsewhere. An increase in Pb concentration from north to south, and an increase in Cd concentration from nearshore to further offshore in the zooplankton mirrors the sediment patterns. Statistical analysis of the chemical and biological data for these samples indicates that relatively small percentages of the biological makeup of the sample can markedly affect the concentrations of Pb, Cd, Ni, and Zn. This is particularly true for the larvacea, ostracoda, and mollusca. Chemical analyses of the exoskeletons of shrimp and the skin of both squid and fish indicate that they generally contain higher metal levels in comparison with the flesh from the same organism. This is probably the result of either adsorption from seawater and/or an internal detoxification procedure employed by the organism. The analysis of a composite sample of squid 'pens' indicates that they contain enriched Cu, Cd, Zn, Pb, and Fe levels in comparison with the skin and flesh. These elevated levels are probably the result of an internal detoxification procedure and/or may represent a means of storing necessary metabolites, at least in the case of Cu and Zn, but can not be attributed to adsorption as the chitinous 'pen' is imbedded in tissue and is not directly exposed to seawater.


Behcet's syndrome in 32 patients in Yorkshire.

Thirty-two patients with Behcet's syndrome were surveyed clinically, radiologically, and immunologically. HLA antigens were determined in a proportion. The patients were culled from a defined geographical area (Yorkshire) with a population of 5 million. 21 patients satisfied Mason and Barnes's (1969) criteria for major disease. 100% had mouth ulceration, 91% genital ulceration, 66% skin complaints, and 63% arthritis (of the nonerosive type previously documented). 3 patients had gastrointestinal involvement, one of whom had proven Crohn's disease. One patient had psoriasis. One patient had a popliteal artery aneurysm resected and one has since had surgery after the development of a tracheo-osophageal fistula. No sacroilititis was found.


Felty's syndrome. Clinical and serological analysis of 34 cases.

Review of 34 cases of Felty's syndrome showed this to be a form of 'super' rheumatoid disease because of the severity of joint disease, the prominence of extra-articular features and the remarkable incidence of infection. The response to splenectomy in these 34 patients was shown by a return towards normal of peripheral blood abnormalities and a decrease in bone marrow granulopoiesis. Although some patients remained free of infection after splenectomy, others have continued to have infections despite the return of white blood cell counts to normal levels. Although splenectomy and subsequent increase in white blood cell levels may be beneficial, our experience suggests that other factors are important in the susceptibility to infection of Felty's syndrome patients. Moreover, we think that splenectomy may have been instrumental in the fatal infection of one of our patients.


Rheumatoid involvement of the lumbar spine.

On stereoscopic examination of the lumbar spines of 6 patients with rheumatoid arthritis and spinal disease we found typical rheumatoid erosions in the apophyseal joints. 2 also had severe asymmetrical disc destruction with associated involvement of the vertebral bodies and scoliosis. In one of these patients who developed Staphyloccocus aureus septicaemia, infection was localized in this part of the lumbar spine.


Ankle joint synoviography in rheumatoid arthritis.

Twenty-six ankles of 23 patients with seropositive or negative arthritis and 24 ankles of 12 cadavers as a control group were studied by contrast synoviography. The main features in the patients were capsule enlargement, hypertrophic synovitis, and connections to tendon sheaths and to the posterior subtalar joint. None of the controls showed capsule distension or irregular outline of the joint cavity, but connections to tendon sheaths and/or to the posterior subtalar joint were present. Other features such as tibiofibular recess, early lymphatic filling, and joint destruction were seen.


Prospective analysis of antiribonucleoprotein antibodies in systemic lupus erythematosus.

A prospective analysis of 50 successive patients with systemic lupus erythematosus, seen over a 4-year period, has been completed. 336 sera were examined for the presence of antibody to ribonucleoprotein using a counterimmunoelectrophoresis assay. Antibody was present in the sera of 16% of patients and was detectable in about the same titre throughout the course of the disease. The presence of the antibody did not appear to identify a subgroup of lupus patients with individual clinical characteristics.


Polymyalgia rheumatica. Assessment of disease activity using erythrocyte sedimentation rate and plasma viscosity.

Comparison of clinically assessed activity of disease with 112 paired readings of the erythrocyte sedimentation rate (ESR) and the plasma viscosity (PV) in 23 patients with polymyalgia rheumatica (PMR) showed the following. (1) A correlation between ESR and PV in both sexes, reaching the significance obtained in a comparison group of patients with rheumatoid arthritis (RA) (109 paired readings), with no significant difference between the PMR and RA groups on analysis of variance of the regression slopes. (2) A degree of scatter of readings around the regression lines so that they could not be used for prediction of ESR from the PV or vice versa. (3) varkappa(2) analysis of normal and abnormal values of ESR and PV which showed a highly significant correlation. However 10 readings were abnormally high for ESR in the presence of a normal PV. 5 of these 10 observations were associated with clinical features of disease activity. 20 readings were abnormally high for PV in spite of a normal ESR with only one instance of clinical activity. These data indicate that it is not possible to provide exact guidelines for a ;safe' level of ESR or PV applicable to the individual patient, and measurement of both these indices of disease activity is recommended.


Effect of age on thickness of adult patellar articular cartilage.

The thickness of left patellar articular cartilages after formalin fixation was studied in a series of autopsies on 82 subjects aged 25-96 years. For each specimen the minimal uncalcified cartilage thickness in a transverse patellar slab was determined separately for a 'lateral' segment and a 'central and medial' segment. In the women the cartilage from subjects more than 50 years old showed progressive thinning with increasing age. This was due to lesions causing disintegration of the tissue and not to matrix shrinkage. It had a strong potential to progress to full-thickness cartilage loss in the older women, and to give an appearance indistinguishable from osteoarthrosis as seen in surgical excision specimens. This progression towards patellofemoral osteoarthrosis in the elderly affects the female population generally, and not just a special subgroup; however, the incidence of clinical symptoms from this cause is not known. In men progressive thinning with age of patellar cartilage in subjects more than 50 years old was less severe, especially so in the case of the 'lateral' segment; a site of full-thickness uncalcified cartilage loss on the left patella at autopsy was seen only occasionally in the older men.


Blood hyperviscosity with reduced skin blood flow in scleroderma.

The vascular complications of scleroderma have previously been attributed to the progressive obliteration of small vessels. Our study was carried out to determine whether abnormalities of blood viscosity occur in this disease, thereby contributing to the ischaemic process. Blood viscosity was measured in 20 patients using a rotational viscometer. At a high rate of shear, blood hyperviscosity was found in 35% of the patients and at a low rate of shear, in 70%. In addition there was a significant increase in the plasma viscosity which implicates changes in plasma proteins (fibrinogen, immunoglobulins) as causing the hyperviscosity. Measurement of the hand blood flow by venous occlusion plethysmography showed reduced flow at 32 degrees , 27 degrees , and 20 degrees C. A unique finding was a delayed recovery of the blood flow after cooling. These observations suggest that the increased resistance to blood flow in skin affected by scleroderma may be caused by an interaction between the occlusive vascular lesion and blood hyperviscosity. In addition, blood flow patterns and hyperviscosity could help distinguish scleroderma from primary Raynaud's disease.


Cardiac abnormality in polymyositis.

Thirteen patients with polymyositis were investigated for the presence of cardiac disease by clinical examination, chest x-ray, electrocardiogram, and systolic time intervals. 5 patients had evidence of cardiac involvement. Compared with the other 8 patients, their polymyositis was more long-standing, more severe, and had remained active. Electrocardiogram usually showed arrhythmias and conduction disturbances, and 4 of the 5 patients had abnormal systolic time intervals indicating left ventricular dysfunction. Left ventricular involvement in polymyositis is more frequent than previously recognized and systolic time intervals are a simple, noninvasive method of detecting this.


Thrombocytosis in rheumatoid arthritis. Recurrent arterial thromboembolism and death.

A patient with rheumatoid arthritis complicated by excessive thrombocytosis and recurrent thromboembolic events is presented. The platelet count correlated well with disease activity and thrombosis occurred when thrombocytosis was marked. The patient died from massive thrombosis of the aorta despite treatment with anticoagulants, corticosteroids, and azathioprine.


Tissue pathology and comparative microanatomy of Onchocerca from a resident of Ontario and other enzootic Onchocerca species from Canada and the U.S.A.

The microanatomy of one male and one female specimen of a zoonotic Onchocera sp in a fibrous nodule excised from the wrist of an Ontario resident, two bovine Onchocerca from Saskatchewan and Manitoba, Canada, and O. cervicalis from the ligamentum nuchae of a horse in Georgia, U.S.A., were compared. In dimensions and cuticular morphology, the three Canadian specimens of Onchocera shared certain features and closely resembled both O. cervicalis and O. gutturosa. The number of cuticular striae in some species of Onchocerca, particularly in male worms, is briefly discussed and its taxonomic value questioned. The Canadian patient visited Radlett, Hertfordshire, England, and then her summer cottage in the Muskoka region, Ontario, prior to the appearance of her symptoms, so that it is uncertain where she acquired the infection. Zoonotic onchocerciasis has yet to be described from Ontario. All nine cases of bovine onchocerciasis (the two described here and seven others) have occurred in Manitoba and Saskatchewan.


The genetics of white-eye, a sex-linked mutant of Aedes (Stegomyia) cooki Belkin.

A mutant designated white-eye (w) is described from a colony of Aedes cooki. White-eye is sex-linked and recessive and the crossover value with the sex locus is 7.18 +/- 1.38%. The gene w has full penetrance and expressivity at all stages of the life-cycle, but in the adults the eyes darken with age to a yellowish colour.


The influence of the gene sb in Culex pipiens on the development of sub-periodic Brugia malayi and Wuchereria bancrofti.

The gene sb (filarial susceptibility, Brugia pahangi) in Culex pipiens controls the development also of sub-periodic B. malayi, but has no influence on the development of periodic Wuchereria bancrofti (Ceylon strain). C.p. fatigans (Kuala Lumpur), C.p. molestus (London) and Aedes aegypti (re fm strain) were all susceptible to the Ceylon strain of W. bancrofti, with susceptibility rate of 90.3%, 92.9% and 52.6% respectively. However, a low proportion of the larvae in A. aegypti developed to maturity, and this mosquito is less well adapted to W. bancrofti than is C. pipiens.


Bacteremia, endocarditis, and the Hancock valve.

Among 373 patients with porcine xenografts, there were 27 instances of exposure of the xenograft to bloodstream or endocardial infection in 22 patients. Nine patients underwent 10 separate insertions of xenografts for active infective endocarditis. There were no early infections or valve failures. Three patients returned with a late prosthetic valve endocarditis (PVE) due to a new infection. There were 6 instances of bacteremia early after xenograft valve insertion with no early infection, no valve dysfunction, and 1 instance of late PVE. Eleven patients had PVE on a porcine xenograft. Blood cultures in the 10 patients treated with antibiotics promptly became negative. There were 3 valve-related deaths: 2 from valve incompetence and 1 from mitral and aortic xenograft stenosis. Our experience suggests that the Hancock porcine xenograft is: (1) as resistant to infection as are rigid prostheses in active infective endocarditis; (2) resistant to early postoperative bacteremias; and (3) easier to sterilize than rigid prostheses and more durable than other tissue valves in the face of PVE.


Patient-related risk factors as predictors of results following isolated mitral valve replacement.

Results following isolated mitral valve replacement in 897 consecutive patients over a twelve-year period were analyzed with regard to the influence of various preoperative patient-related risk factors. Actuarial data analysis allowed definition of major preoperative, etiological, clinical, and hemodynamic correlates to both perioperative and long-term postoperative patient survival. Patient age below 60 years, preoperative New York Heart Association Functional Class of III or less, cardiac index greater than 2.0, and left ventricular end-diastolic pressure of less than 12 mm Hg were all highly significant correlates of improved perioperative as well as long-term patient survival. Patients whose predominant functional lesion was mitral insufficiency had only a 53% five-year survival (187 of 352 patients) following mitral valve replacement as opposed to 70% (521 of 745 patients) for those who had mixed or stenotic mitral lesions. Primary ischemic mitral dysfunction was associated with only 31% five-year survival (17 of 54 patients) after mitral valve replacement in contrast to 69% (480 of 695 patients) for patients with rheumatic mitral lesions. The presence of occlusive coronary artery disease coexisting with, but not the primary cause of, mitral dysfunction was associated with decreased perioperative and late postoperative survival. Results support both earlier operative intervention and wider use of associated procedures, ie, coronary bypass grafting, with mitral valve replacement. Recognition of major preoperative patient-related risk factors should enhance survival following this procedure.


The terminal pathway of the lymphatic system of the human heart.

Aantomical dissections in 9 human cadavers revealed the terminal pathway of the lymphatic system of the left ventricle to be constituted mainly by channels emptying into the right angulus venosus (junction of the internal jugular and subclavian veins) at the base of the right side of the neck. This observation has clinical implications because it has been shown that a sampling of cardiac lymph provides the best method for analyzing myocardial metabolic abnormalities and that drainage of cardiac lymph alleviates the myocardial changes produced by ischemic injury.


Left ventricular approach to multiple ventricular septal defects.

Multiple muscular ventricular septal defects were closed through an apical left ventriculotomy in 11 patients. The patients were divided into two groups: Group 1, 8 patients who had transposition of the great arteries, and group 2, 3 patients without transposition. There were 4 deaths in Group 1 and non in Group 2. Two of the deaths were caused by a hypoplastic right ventricle, 1 by airway obstruction, and 1 by heart failure and pulmonary edema in a patient who had additional unrecognized muscular defects. An apical left ventriculotomy provides excellent exposure of the septum. The field is not obscured by trabecular bands or papillary muscles. Although 1 patient died because of residual VSDs, this approach, compared with previously described methods, minimizes the risk of unrecognized defects.


Correction of aortic coarctation in neonates: mortality and late results.

To determine those factors that affect mortality and to analyze long-term results, the records of 44 infants who underwent repair of aortic coarctation at less than 90 days of age were examined. There were 14 operative and 8 late deathes (mean, 4.3 months postoperatively). Subsequent operation, generally to repair or palliate associated anomalies, was required 22 times in 20 patients and was a source of considerable mortality. There is evidence that earlier total repair of associated anomalies might improve survival. Sufficient data were available on 17 of the 22 survivors to assess long-term results. The outcome was considered excellent in 8 patients, fair in 4, and poor in 5. Revision of the coarctation repair due to growth failure of the anastomosis was required in 1 patient. Aggressive surgical management is recommended in these infants because, despite a high early mortality, a considerable proportion of excellent results can be anticipated in what is otherwise a hopeless situation.


Results and complications of intraaortic balloon counterpulsation.

During the forty-month period ending July, 1976, intraaortic balloon counterpulsation was used as an adjunct to medical or surgical therapy in 273 patients. Thirty-seven developed complications. Limb ischemia occurred in 16; it resolved in 12, resulted in gangrene of the toes in 1 and leg gangrene in 2, and was the casue of death in 1 patient. Aortic dissection was confirmed in 7 patients and strongly suspected in another 4. Eight of the 11 patients with dissection underwent cardiac procedures with heparinization at two days to three months after balloon insertion with no untoward effects. Septicemia developed in 2 patients, 1 of whom died of cardiogenic shock. Localized groin sepsis occurred in 8 patients, 2 of whom required removal of infected Dacron graft material. Awareness of the complications of balloon insertion, proper attention to details of balloon management at the time of insertion and removal, and continuous monitoring through a central-lumen balloon should decrease the incidence of complications.


A pulsatile assist device (PAD) for use during cardiopulmonary bypass.

A pulsatile assist device (PAD) has been developed to convert roller pump flow to pulsatile flow in a simple fashion. The device can also be used as an arterial counterpulsator before and after cardiopulmonary bypass. The PAD has been used in 125 adult patients undergoing open-heart operations for coronary artery or valvular heart disease or the combination. Ninety-two patients were in New York Heart Association Functional Class III or IV or had ejection fractions of less than 0.3. The PAD functioned as a hemodynamically effective arterial counterpulsator before and after perfusion. All patients were successfully weaned from bypass with the PAD. There has been 1 intraoperative death and 2 late deaths. Only 1 patient had a perioperative myocardial infarction, and this person was successfully treated with intraaortic balloon pumping. We believe the PAD is a simple and reliable device for intraoperative counterpulsation and for the creation of pulsatile cardiopulmonary bypass. More important, use of the PAD may decrease both the incidence of perioperative myocardial infarction and the need for postoperative intraaortic balloon pumping.


Coronary flow distribution and dynamics during continuous and pulsatile extracorporeal circulation in the pig.

Four extracorporeal perfusion conditions (continuous beating, continuous fibrillating, pulsatile beating, and pulsatile fibrillating) were tested for 15 minutes each in pigs. Coronary flow, endocardial-epicardial flow ratio, phasic coronary flow, myocardial oxygen consumption, and myocardial lactate extraction were measured. No significant differences in any of these variables were found between pulsatile and continuous flow states in either fibrillating or beating hearts (p greater than 0.05). In both fibrillating conditions, significant elevations of myocardial oxygen consumption and decreases in endocardial-epicardial flow ratios were found (p less than 0.05). Lactate extraction occurred in all conditions, and phasic coronary flows were similar in both beating conditions. These data suggest caution in the expectation that pulsatile perfusion will reverse the coronary flow and myocardial oxygen consumption changes seen with fibrillation.


Hypothermia in conjunction with hyperbaric oxygenation in the treatment of massive air embolism during cardiopulmonary bypass.

Massive gas embolism during cardiopulmonary bypass is a rare but ever-present danger. Following this catastrophic event, the immediate institution of core cooling on bypass may be advantageous. The remarkable complete recovery of our patient is attributed to this technique, which was used in conjunction with standard therapy.


Cytosine arabinoside binding to human plasma proteins.

The interaction of cytosine arabinoside (Ara-C) with human plasma proteins was investigated by means of ultrafiltration and ultracentrifugation. The results obtained with both methods did not differ significantly. Ara-C binding was studied at plasma levels within the therapeutic range (0.005-1.0 mg/l). It appeared that 13.3% (SD: 2.2%) of Ara-C in the plasma was bound to proteins. The percentage of bound drug was independent of the drug concentration, at least in the therapeutic range.


Inhibiting effect of droperidol compared with verapamil on the myocardial fiber calcium exchange determined by a simple physiological procedure.

A simple procedure was employed in order to quantify myocardial calcium antagonism by the neuroleptic agent droperidol. Droperidol blocked recovery of excitability induced by isoproterenol in isolated rabbit hearts depolarized by KCl. This was also observed with verapamil, a known calcium inhibitor, though at much lower concentrations. Considering that isoproterenol excites depolarized tissue by favouring calcium conductance and that droperidol as verapamil lack beta-adrenergic blocking properties, it is infered that droperidol hinders myocardial membrane permeability to calcium ions in a manner similar to that of verapamil. This action of droperidol, together with its known inhibiting effect on the rapid Na entrance, may explain the mechanism by which it affects cardiac chronotropism.


A rapid in vivo technique for preliminary screening of antiarrhythmic agents in mice.

The search for new and better antiarrhythmic agents is complicated by the fact that currently there is no generally accepted, rapid, highly reproducible, in vivo screening technique which allows the use of large numbers of small animals for the purpose of statistical evaluation. Most of the methods available for use with small animals employ visual observation of the animal to assess electrophysiological events occurring in the heart. A rapid, inexpensive, in vivo screening technique is discribed, using aconitine as the arrhythmogenic agent. Arrhythmias induced by aconitine were measured by electrocardiogram (lead II). The times to onset of initial cardiac arrhythmias and ventricular tachycardia were determined and compared for significance in animals pretreated with physiological saline (control group), standard antiarrhythmic agents, and two drugs lacking antiarrhythmic activity. The results indicate that the method is a sensitive, rapid technique for preliminary in vivo screening of antiarrhythmic drugs.


The effect of quinidine, propranolol and their combination on experimental atrial and ventricular arrhythmias.

The comparative antiarrhythmic activity of quinidine, propranolol and the combination of these two drugs was studied in experimental atrial and ventricular arrhythmias in the dog. Quinidine, but not propranolol, suppressed atrial arrhythmias produced by topical application of aconitine to the atrium, as well as the ventricular arrhythmias that developed approximately 20 hr following coronary artery ligation. When the two drugs were coadministered, synergism occurred in the atrial arrhthmias but not in the ventricular arrhythmias. Some possible mechanisms of action of these drugs are discussed. The change in response to quinidine by coadministration with propranolol may have resulted in part from suppression of atrial automaticity in the aconitine experiments and from further slowing of ventricular conduction in the coronary artery ligation experiments. Both effects might have occurred as a result of myocardial beta adrenergic receptor blockade.


Hypotensive action of an intra-nasally applied angiotensin II-antagonist.

Intranasal administration of the specific angiotensin II-antagonist (1-NSuc-5-Val-8-Phg) A II was investigated in anaesthetized rats with different forms of experimentally elevated blood pressure. Renin- or angiotensin II-induced blood pressure increases were markedly reversed by the angiotensin II-antagonist applied intra-nasally. In rats with acute accelerated elevation of blood pressure the analogue induced also a significant decrease. No change could be observed in rats with chronic renal hypertension.


Biological evaluation of some biphenyl analogs of acetyl-seco-hemicholinium No. 3.

The oxygen atoms in the esteratic moiety of acetyl-seco-hemicholinium No. 3 (AcHC-3) were replaced with carbon to form the ether, ketone and aliphatic analogs. Also, the thio and acetylthio-seco analogs of hemicholinium No. 3 (HC-3) were studied. When evaluated in the rabbit sciatic nerve-gastrocnemius muscular preparation all of the analogs caused neuromuscular blockades in two or three separate phases. The first phase of blockade caused by the ketone and thio analogs was rapid in onset and reversed by neostigmine. It was presumably competitive in type. The first phase of blockade caused by the ether and aliphatic analogs was increased by neostigmine and was concluded to be of the non-competitive type. All analogs caused a second phase of blockade that was reversed by choline and is typical of HC-3. A third blockade was found following the ether and ketone analogs. All of the analogs were more active as inhibitors of the true and pseudocholinesterases than was HC-3. All of the analogs were much less potent as inhibitors of acetylcholine synthesis than was AcHC-3. The implications of these findings are discussed.


Morphine and methadone-induced antinociception in rats permanently depleted of brain dopamine.

The purpose of the present study was to evaluate the role of brain norepinephrine (NE) and/or dopamine (DA) in the production of the antinociceptive effects of morphine and methadone. Rats were permanently depleted of brain NE and/or DA via 6-hydroxydopamine (6-OHDA) treatments at two weeks of age. Six to eight weeks later, the antinociceptive activity of morphine and methadone was determined in control, NE and DA-depleted, and DA-depleted rats by tail-flick methods. Both dose-response and time-duration studies were conducted. The data obtained suggested that DA was important to morphine, but not to methadone-induced antinociception. However, this relationship appeared contingent upon the level of DA-depletion. An antagonism of morphine's effects was observed when DA levels were down by at least 85% whereas a facilitation of morphine's effect occurred when DA levels were 50% or less. These findings were discussed in relation to more recent concepts suggesting that: 1) DA-related behaviors are contingent upon a balance between excitatory and inhibitory DA neuron pools, and 2) antinociception may (in relation to DA) also be controlled via a balance between this system (DA) and NE systems. Thus, it was suggested that the potency of morphine's antinociceptive effects appears contingent upon a balance between one or more of these neuron pathways.


Behavioral despair in mice: a primary screening test for antidepressants.

A depressed state can be induced in mice by forcing them to swim in a narrow cylinder from which they cannot escape. After a brief period of vigorous activity the mice adopt a characteristic immobile posture which is readily identifiable. Immobility was reduced by tricyclic antidepressants, monoamine oxidase inhibitors and atypical antidepressants, as well as by electroconvulsive shock. Psychostimulants also reduced immobility but in contrast to antidepressants caused marked motor stimulation. Immobility was not affected by minor or major tranquilisers. These findings, closely parallel to those we have previously reported in rats, suggest that the procedure is selectively sensitive to antidepressant treatments. The mouse procedure is, however, more rapid and less costly than that with rats and is thus more suitable for the primary screening of antidepressant drugs.


Inhibition of glucose absorption by 3-phenylpropylaminoguanidine-HCl (SaH 43-522) in laboratory animals.

The present studies were undertaken to define the effects of 3-phenylpropylaminoguanidine-HCl (SaH 43-522 or 43-522) on glucose active transport in the gastrointestinal tract. A comparison with phenformin (DBI) was made in certain studies. SaH 43-522 is 2 to 3 times more potent than DBI with regard to its inhibitory effect on glucose active transport in the gastrointestinal tract of rats. The activity lasts for 5 hr after oral administration. SaH 43-522 also inhibits intestinal glucose absorption in the hamster, guinea-pig, dog, and monkey in either in vitro or in vivo systems. SaH 43-522 differs from DBI in that when glucose active transport is studied in vitro by adding drug into the incubation fluid, DBI is active only when the drug is present in the incubation fluids on both the mucosal and serosal sides, whereas SaH 43-522 is active in inhibiting intestinal glucose active transport when the drug is present in mucosal fluid only.


Autonomous growth fluctuations of the methane oxidizing bacterial strain M 102 in batch and continuous culture.

The growth rates of the methane oxidizing strain M 102 were unstable. In unlimited batch cultures they ranged from 0 to 1.4 d-1 with most frequent values around 0.25 d-1. The yield coefficients were between 0.1 and 1.6 mg dry weight per mg methane and varied from 1.1 to 0.4 even in a continuous culture with the limiting substrate in the gas phase. It was possible to prove intermittent release and uptake of organic compounds by the definition of a "net" yield coefficient and its theoretical boundaries. The response of the fluctuations to varying dilution frequencies and culture volumes showed analogies to controlled systems. The simultaneous variations in the age distribution and in the excretion pattern revealed the dependence of the dividing stages on a product of the young cells. The mathematical description of the findings suggests that the young cells favor division at their own disadvantage. The consequent autonomous synchronisations are the reason for the unstable growth rates of strain M 102.


Recombination after protoplast fusion in the yeast Candida tropicalis.

Candida tropicalis protoplasts obtained by snail enzyme treatment were induced to fuse by the use of polyethylene-glycol. Heterokaryons formed by two auxotrophic strains were selected by complementation on minimal medium. These heterokaryons were unstable and readily dissociated into their nuclear components. Under appropriate conditions, the parental nuclei of an heterokaryon fused. The homokaryon so obtained was unstable and segregated into various types of auxotrophic and prototrophic recombinants.


The roles of isomers of phytoene, phytofluene and zeta-carotene in carotenoid biosynthesis by a mutant strain of Scenedesmus obliquus.

Considerable changes in pigment composition occur during a period of 10 h when dark-grown cultures of PG1, a zeta-carotenic strain of Scenedesmus obliquus, are illuminated. These changes are consistent with a biosynthetic pathway in which 15-cis-phytoene is converted via 15-cis-phytofluene and 15-cis-zeta-carotene into all-trans-zeta-carotene and trans-bicyclic carotenoids. The findings also support the view that the xanthophylls lutein and zeaxanthin are formed from the corresponding carotenes and are especially important in the development of a normal chloroplast structure.


Electron microscopic investigation of the hydrogen-oxidizing acetate-forming anaerobic bacterium Acetobacterium woodii.

Acetobacterium woodii is a Gram-positive anaerobic nonsporeforming bacterium able to grow on H2 and CO2 as sole sources of energy. The product of fermentation is acetic acid. Fine structural analysis showed rod-shaped flagellated cells, and coccoid cells without flagella arranged predominantly in pairs and chains. The cell wall was found to be composed of three layers. The cell surface exhibited a periodic array of particles consisting of subunits. The cytoplasmic membrane showed particles either in random distribution or in a hexagonal pattern. Intracytoplasmic membranes were rarely observed, whereas inclusion bodies of varying shapes, predominantly in an uncommon disc-shape, could frequently be observed. Their content was dissolved in ultrathin sections indicating hydrophobic nature.


Morphology and histochemistry of helicine arteries in the corpora cavernosa penis of mice.

The epitheloid modified walls of helicine arteries are built of tightly arranged specialized smooth muscle cells (epitheloid cells). They are polygonal in shape, but do not branch out. The number of myofilaments is markedly reduced, whereas cell organelles are well developed (mitochondria, Golgi regions, rough endoplasmic reticulum). Myofilaments are gathered to bundles with no orientation as to their direction. Regular dense patches and attachment zones do occur. The cell surface is provided with caveolae (surface vesicles) and a basal lamina. Where epitheloid cells are joined together, they share a single basal lamina in common. In circumscribed regions basal lamina material is completely absent, and the cell membranes approach to form a 150 A gap (paired cells). Endothelial cells are rich in cytoplasmic filaments and show only a few transport vesicles. In particular areas a basal lamina is absent, and epitheloid cells and endothelial cells are joined together leaving a 200 A wide cleft. Fluorescence histochemistry shows that helicine arteries are provided with an extremely dense network of adrenergic nerves located at the medio-adventitial border. Epitheloid cells, like ordinary vascular smooth muscle cells, show a postive ATPase reaction, but lack any histochemically demonstrable 5'-nucleotidase activity. Endothelial cells in helicine arteries react on unspecific alkaline phosphatase, while the endothelium of deep arteries and of the cavernous spaces does not.


Electron microscopy of the mouse optic nerve: a quantitative study of the total optic nerve fibers.

The total number of myelinated and unmyelinated nerve fibers was counted in a montage of electron micrographs prepared to cover the entire profile of the mouse optic nerve in transverse section. Many astrocytic processes form a barrier structure all around the optic nerve. As a whole, the mouse optic nerve consists of one fascicle where the nerve fibers, the glia cells and their processes, and the capillaries are fitted closely together to fill substantially all of the available space. No tissue space accompanied with connective tissue septa penetrates into the fascicle, except for those situated around the arteriole and venule. The total number of 64,746 myelinated nerve fibers in the optic nerve in one side was counted. This corresponds to about 98.8% of the total number of the optic nerve fibers. The total number of 807 unmyelinated nerve fibers was also counted. This corresponds to about 1.2% of the total nerve fibers. The external diameter of every myelinated fiber, including the myelin sheath, was measured on the montage micrograph and its frequency distribution was examined. The diameter of the myelinated fibers ranges from 0.3 to 4.2 mu and its mean value is 0.96 mu. The frequency distribution of fiber diameter is unimodal with a peak at 0.7 to 0.9 mu. A regional heterogeneity in fiber size is found in the optic nerve. The nerve fibers in the peripheral area of the nerve are relatively small and uniform in diameter, whereas those in the central area show a fairly wide range in diameter.


On the vascular architecture of the carotid labyrinth in Cynops pyrrhogaster and Onychoactylus japonicus.

The fine vascular arrangement of the carotid labyrinth in two species of urodeles, Cynops pyrrhogaster and Onychodactylus japonicus was investigated. India ink-gelatin injected preparations were examined under the dissecting microscope. Resin casts of the blood vessels prepared using the method of MURAKAMI (1971) were observed in the scanning electron microscope. In both species, the common carotid artery terminated in the central chamber from which arose two retia mirabilia, i.e. an external carotid rete and an internal carotid rete. The external carotid artery arose recurrently from the external carotid rete, whereas the internal carotid artery received vessels from the internal carotid rete which apparently occupied more than two thirds of the carotid labyrinth. The present observations indicate that the previous descriptions of the urodele carotid labyrinth should be corrected: a vascular ring exists around the common carotid artery and the latter shows a corresponding narrowing at the entrance to the carotid labyrinth; the vascular ring forms the most proximal part of the external carotid rete; the central chamber occupies only a part of the proximal end of the carotid labyrinth; the internal carotid rete and the external carotid rete constitute a continuous rete mirabile; and a distinct furrow exists in the boundary between these two portions of the rete mirabile. Individual variations were frequently encountered, but were confined to the external carotid artery and its tributaries. The complicated and elaborate vascular architecture of the amphibian carotid labyrinth suggests that this organ should exert blood-flow regulating the probably other unknown functions as an effector organ in addition to its accepted activity as a chemo- and baro-receptor.


Similarities of cellular receptors for interferon and cortisol.

Cellular receptors are molecules located on the cell membrane. Their function is to bind different molecules to the cell surface. These molecules can penetrate into the cytoplasm and trigger cellular changes. One kind of such bound molecules are interferons and corticosteroids. Until very recently very little was known about interferon's receptors on the cell surface, mechanisms of interferon's binding to them or about kinetics of such binding. On the basis of results published elsewhere and on the basis of experimental results, the authors suggest: 1) receptors for interferon and cortisol are glycoproteins located on the cell surface, 2) in analogy with PHA receptors they are chemically sialoglycoproteins, 3) binding kinetics of cortisol and interferon is similar, 4) interferon and cortisol compete for cellular receptors, 5) binding of cortisol or interferon is dependent on allosteric configuration of receptor molecules.


Purification of mouse interferon on specifically purified immunoadsorbent.

A one-step purification procedure using affinity chromatography on purified anti-interferon antibodies makes possible to obtain highly purified interferon preparations. Antibodies against purified mouse fibroblast interferon were covalently bound to activated CNBr-Sepharose 4B. This immunoadsorbent had a binding capacity of 125,800 mouse fibroblast interferon units per 4.8 ml of gel. The binding capacity for mouse leukocytes was similar while for serum interferon it was lower. When analyzed in polyacrylamide gel, the electrophoretic profiles of purified IF had a similar shape to that of unpurified IF. The results of this purification procedure are not influenced by volume, biological activity and/or purity of the starting material.


Induction and properties of guinea pig serum interferon. Preliminary report.

Guinea pigs, 250-350 g body weight, both sexes, were injected with 5X10(8.5) EID50 NDV (Radom strain) intracardially and intraperitoneally simultaneously. The animals were bled by cardiac puncture 0, 3, 6, 12, 24 and 48 hours after injection. After virus inactivation, serum interferon titration was performed in cultures of guinea pig embryo kidney cells with 50 percent plaque inhibition test using VSV. The highest interferon titer (64 u./ml) was found after 6 hours of inductor injection. Interferon titer decreased quickly and after 12 hours it was lower than 16 u./ml. Guinea pig serum interferon induced by NDV was resistant to pH 2 and 56 degrees C during 1 hour. Interferon was inactivated by trypsin. The decribed interferon did not protect heterologous species cells (swine) against Teschen Disease Virus infection. Other properties of this interferon are being studied.


Kinetic and metabolic studies on the priming effect of interferon in L cells.

In cultures primed by interferon pretreatment before stimulation by polyriboinosinic-polyribocytidylic acid interferon was detected one hour earlier, its production followed and enhanced pattern and became resistant to actinomycin D 30 min sooner than in unprimed cultures. The kinetics of development of the primed state was found to be a time-and dose-dependent phenomenon. The continuous presence of interferon during the pretreatment period was not required for the development of the primed state. Actinomycin D at a concentration inhibitory for nuclear RNA synthesis did not influence the development of priming. Higher concentrations of the drug and long term alpha-amanitin or cycloheximide pretreatments, inhibitory for heterogeneous nuclear RNA synthesis, prevented the establishment of the primed state.


The effect of interferon on chicken spleen lymphocytes.

The inhibitory activity of chicken interferon has been investigated on phytohemagglutinin (PHA)-induced DNA synthesis of chicken spleen lymphocytes inoculated with type 12 adenovirus and was purified by selective adsorption on Na-Al-silicate. As a control, the culture fluid of chicken leukocytes purified in the same manner was used. In some instances the control preparation also showed a slight inhibitory effect. To prove that the immunosuppressive activity of our interferon preparation was indeed due to its interferon content both the interferon and the control preparation were purified further by chromatography on Sephadex G 100 superfine gel. Only the fractions with antiviral activity of interferon preparation inhibited the PHA-response of the lymphocytes. The fractions with the same molecular weight of control preparation were without effect.


Effect of poly I:C on cell proliferation in vivo.

Female Swiss albino mice were injected intraperitoneally with poly I:C1 microgram/g body weight. The animals were killed 2, 12, and 24 hr after the injection of poly I:C. Half an hour before the death of animals they were reinjected intraperitoneally with 3H-thymidine. Fragments of ileum were excised. The quantification of autoradiographs included the counting of labeled cells, mitotic cells as well as the recording of cell position along the ileal crypts. The spatial distribution of both the mitotic and DNA-synthesizing cells of colonic crypts were affected by poly I:C at neither of time intervals between the injection and the death of animals. On the other hand, the parameters of cellular proliferation, i.e. mitotic and labeling indices, decreased significantly 12 and 24 hr after the injection of poly I:C, being unaffected 2 hr after the injection.


Swine cell systems as interferon producers. IV. Comparative studies on the correlation between virulence of different Newcastle disease virus strains and their potency as interferon inducers.

Comparative studies concerning a correlation between virulence of various Newcastle virus strains and their interferon-inducing potency confirmed that such a correlation existed. The nearly avirulent La Sota strain of NDV was the poorest interferon inducer, the virulent Hertfordshire strain manifested a very good inducing potency. However, the most virulent J.B. strain virus was a poorer interferon inducer than the Hertfordshire strain. This should not be viewed as contradictory to the conclusion of the correlation between virulence and interferon-inducing ability of NDV since the highly virulent strain might destroy faster the interferon-producing cells, before the latter produced the maximum interferon quantity which they potentially could produce.


Why HeLa cells do not produce interferon?

The investigation was carried out with HeLa cells which were not sensitive to antiviral action of human diploid cell interferon and do not produce interferon after induction with Newcastle disease virus. Identity of this line was confirmed by determination of stable genetic markers such as isoenzymes and histocompatibility antigens. On electrophoresis of lysed HeLa cells the following human red cell enzymes phenotypes were found: PGM (1-1), AP, EsD, and GTP. It was shown that on the surface of HeLa cells membranes HLA antigens are expressed: A28, BW35, A3. The results are in agreement with those which were obtained from Henrietta Lack's family study. Chromosome G-banding analysis revealed disproportion between the number of chromosomes connected with production and action of interferon and chromosomes which are supposed to control these processes.


Levels of complement during interferon induction.

Further data were obtained in support of the finding that the levels of interferon and complement show a negative correlation after induction of interferon in vivo. Experiments with selective chelating agents showed that the activation of complement occurs by the by-pass mechanism. Preliminary results indicate that interferon itself can reduce the level of complement in vivo. Experiments are underway to verify in rats the results obtained in mice.


Some biological activites of rabbit anti-interferon serum.

After prolonged immunization of rabbits with a semipurified mouse interferon preparation in Freund-incomplete and/or Al-Span-Oil-adjuvant a specific interferon neutralizing immunoglobulin was obtained from antiserum. The specific activity of the antiserum and immunoglobulin was confirmed in tests in which the interaction of antibodies with the cell-surface was ruled out. The antiserum (and the immunoglobulin) neutralized both the anti-viral and the cell-growth inhibitory activity of interferon. The "slow" and the "fast" fractions of purified interferon preparations were equally sensitive toward the neutralizing effect of antibodies. On the other side, the reaction of heat-inactivated interferon with the antiserum did not diminish its neutralizing activity suggesting a destruction of interferon-antigenic sites.


Treatment and prevention of acute viral respiratory infections in children with leukocytic interferon.

Children with viral respiratory infections and healthy contacts received treatment and prophylaxis with leukocytic interferon. The results emphasize the effectiveness of treatment when interferon is given on the first or second day of the disease. In these cases the course is mild, of short duration, and without complications. Conversely, the clinical course in children who did not receive interferon was more severe; the disease lasted longer, and complications were not uncommon. Prophylactic instillation of interferon succeded in protecting 85.2 percent of contacts; those who contracted the infection had a mild disease with insignificant complications. No allergic or intoxication phenomena were observed in children receiving leukocytic interferon for treatment or prophylaxis.


Electromyographic insertional activity mechanically provoked in the biceps brachii.

Clinically, some electromyographers have felt that electrical activity provoked by needle insertion becomes prolonged prior to the development of positive sharp waves and fibrillation potentials in pathologic conditions. The significance of this is unclear as this electrical activity has not been quantitatively studied in normal subjects. To approach this problem, this study was designed to evaluate insertional activity in normal subjects. A mechanical electrode inserter was designed and assembled. Insertional activity was recorded and analyzed in 20 normal subjects. Sharp spike activity, a component of the total insertional activity, was found to continue for 48 +/- 18 msec following the cessation of electrode movement in the biceps brachii.


Bilateral injury to the hypoglossal nerve.

The hypoglossal nerve supplies motor function to the tongue. Two cases of bilateral, post-traumatic injury to the hypoglossal nerve are described. Physical and electromyographic examinations in these cases showed evidence of bilateral injury to the hypoglossal nerve as well as the absence of injury to the other closely associated cranial nerves. (A review of the English literature in the past 20 years shows no cases of isolated bilateral damage to the hypoglossal nerve, although there are several cases of unilateral or combined injury.) The disabilities resulting from hypoglossal nerve palsy and the importance of the tongue in normal swallowing are discussed. Two possible causes of hypoglossal nerve palsy are offered.


Electromyographic biofeedback as a physical therapeutic adjunct in Guillain-Barré syndrome.

The case history of a patient with polyradiculoneuritis with symmetrical ascending motor weakness and distal sensory impairment (Guillain-Barré syndrome) is reviewed in relation to a new application of electromyographic biofeedback. In addition to the normal therapeutic procedures, a special device was used to control the amount of therapeutic exercise delivered to the patient in one muscle grouping. Results indicate that this type of adjunctive therapy adds to the current methods of evaluation and treatment of maintaining a patient's interest over a lengthy hospitalization, allowing the therapist to attend several patients simultaneously, and enabling continuous quantitative evaluation of the patient's progress.


A case of cortical deafness.

At the age of 42 Lothar H. suffered a left-sided ischaemic brain lesion with transient aphasia, followed at the age of 49 by a right-sided ischemic infarction, which caused a continuous inability to understand spoken language and to identify tones and noises. He was still able to discriminate between single qualities of pure tones. The ERA-results showed the central acoustic pathways of the brain-stem to be intact. The occurrence of cortical deafness following bilateral lesions of the acoustic cortex and adjoining cortical centres supports the view that human auditory recognition is represented in both temporoparietal areas.


[The syndrome of auditory agnosia. A case report and an attempt of neuropsychological qualification (author's transl)].

Proceeding from the neuropsychological examination of a patient with an exceptionally selective impairment of auditory gnosis of vascular origin, we make an attempt to analyze structurally the syndrome of auditory agnosia, a study of which has been neglected in comparison with analyses of visual agnosia. In our analysis we refer to 28 case reports, documented in the literature. Decisive syndromal points of view are: a) there is an absence of significant audiological deficiencies; b) errors of the acoustic-discriminative type prevail in auditory-visual matching tasks; c) the gnostic deficit is modality specific; d) the same items are variably reproduced on repeated presentation; e) there is marked fluctuation of performance; f) there is exceptional irreversibility of the impairment; g) amusia is a more or less obligatory accompanying phenomenon; h) in cases of vascular origin there is always a history of repeated temporal lobe damage, this damage being predominantly in the form of bilateral lesions. This analysis indicates a close structural analogy to the syndrome of perceptive visual agnosia. We place great importance in the relationship between approaches and models of cognitive psychology (Neisser, 1967) which we see as important for further theoretical development in neuropsychology.


[Perception and evaluation of symptoms in hypochondria (author's transl)].

Hypochondriacal perception and evaluation of symptoms are discussed as an abnormal cognitive process. From a phenomenological viewpoint, a self-centered focussing on the perception of bodily sensations and a restriction of risk-taking behaviour is emphasized. In behavioral terms, several cognitive mechanisms and concepts including perceptual awareness, selection, 'set' as well as signal-detection, decision processes and 'anchoring' factors are considered to be important aspects of hypochondriacal perception.


[The phenomenon of periodic alternating eye deviation (author's transl)].

On the basis of a clinical and electrooculographic observation the phenomenon of periodic alternating eye deviation is discussed. The few cases in the literature are reviewed and the topography of the lesions causing eye deviation is considered.


[Statistics and reinvestigation of the 4/s variant of basic EEG activity (author's transl)].

We selected our patients from 1961 to 1973 (60 500 patients, 66 661 EEG recordings) for the 4/s variant of EEG activity according to the characteristics described in the literature. In 1.9% (115 patients) this EEG variant was evident. In addition, 25 out of 50 variant patients from this group were reexamined. In regard to amplitude, local distribution, frequency concentration around 4/s, our findings concur with those of other authors. Slower frequencies of the 4/s variant occur more often at advanced age. The age median was 32.7 years compared with 42.5 years in the rest of the cases examined in the clinic and out patient clinic over a period of 15 years. This age difference is significant (P less than 0.001). The 4/s variant did not occur more often in men than in women. Only the most common clinical diagnosis, vascular headache or migraine (36%), occurred with significantly higher incidence in 4/s variant patients (P less than 0.001). Other clinical diagnoses showed the same distribution in EEG variant patients and other patients of this clinic. EEG reexaminations carried out over a long period of time are an important criterion in evaluating 4/s activity in the posterior regions of the cranium as a--possibly constitutional--4/s variant of basic cerebroelectric activity.


[Secretion of radioactively labeled amino acids into the digestive tract. 4. 14C label and 14C-leucine in the digestive tract following subcutaneous injection of 14C-leucine in rats after ligation of the pancreas].

Secretion into the Gastro-Intestinal Tract of Amino Acids Labelled with Radioactive Isotopes. (4) 14C-Labelling and 14C-Leucine in the Gastro-Intestinal Tract after Subcutaneous Injection of 14C-Leucine to Rats with Tied-off Pancreatic Gland.


[The optimal vitamin B 6 requirement of early weaned piglets].

In a two-period rearing trial (1st to 24th and 24th to 45th experimental day) using 72 early-weaned piglets, the optimal vitamin-B6 requirement was determined on the basis of different performance criteria and biochemical parameters. In the corresponding live weight ranges of 3.5 to 10 kg and 10 to 21 kg, the animals allotted in 6 groups were ad lib. fed a prestarter and starter feed, respectively containing 0.5, 1.2, 2.0, 2.8, 3.5 and 6.6 mg vitamin B6 per kg dry matter. For adequate feed intake and weight development, a dietary vitamin B6 content of 2.0 mg/kg and 1.2 mg/kg proved necessary for the 1st and 2nd part of the experiment, respectively. An optimal intermediary metabolic situation and thus an optimum vitamin B6 requirement covering, which was derived from the renal xanthurenic acid excretion and the SGOT activity, was attained only at a vitamin B6 supply level of 3.5 and 2.8 mg/kg for the 1st and 2nd experimental periods, respectively. This corresponds to an average vitamin B6 requirement per animal and day of 0.8 mg for the weight range 3.5 to 10 kg, and of 1.9 mg for the weight range 10 to 21 kg.


Togavirus RNA: reversible effect of urea on genomes and absence of subgenomic viral RNA in Kunjin virus-infected cells.

Electrophoretic analyses showed that no RNase-sensitive RNA smaller than the genome was specified by the flavivirus Kunjin in infected Vero cells during the period of maximum RNA and protein synthesis. In contrast, RNA extracted from Sindbis virus-infected cells under similar conditions included the expected 42S RNA (equivalent to the genome) and the smaller 26S (interjacent) RNA. Treatment of the genome of both togaviruses with 12 M urea produced a reversible (possibly conformational) change; measurement of the molecular weights of the treated RNAs by co-electrophoresis with fully denatured ribosomal RNA markers in SDS-polyacrylamide gels yielded a value of 2.1 X 10(6) if 8 M urea was incorporated in the gels and 4.2 X 10(6) if urea was omitted from the gels. These results indicate that flavivirus messenger RNA is represented solely by the intact genome of m.wt. 4.2 X 10(6).


The cerebrospinal fluid of rabbits infected with Borna disease virus.

Rabbits were inoculated intracerebrally with Borna disease virus infected brain suspension or tissue culture extracts. In 30 per cent of the diseased animals infectious virus was present in the cerebrospinal fluid (CSF). The CSF had increased numbers of lymphocytes and an elevation of the protein concentration, mainly due to an increase in gamma-globulins, was measured. The gamma-globulins were of oligoclonal character and reacted with a borna disease virus specific antigen of infected brains or tissue culture cells. The antibody titers in the CSF were of similar level to those in the serum. In comparison, those of the CSF of naturally infected horses always exceeded the serum titers. Injection of tracer substances revealed that no drastic damage to the blood-brain barrier was caused during the disease. The results suggest that antibodies detected in the CSF are locally produced. The significance of these findings for the pathogenesis of Borna disease is discussed.


Cold adapted variants of influenza A. II. Comparison of the genetic and biological properties of ts mutants and recombinants of the cold adapted A/AA/6/60 strain.

The genetic and biological properties of 13 recombinant influenza A clones derived at 25 degrees C from the A/AA/6/60-cold variant (by crosses with 4 different wild type strains) were compared with a set of 5-FU induced ts-mutants. The 5-FU mutants had previously been placed into 7 complementation-recombination groups; the A/AA/6/60-cold parent (PI-7) and the 12 cold recombinant clones which were ts were shown to share a lesion with only one of these groups. The parental strain and 5 recombinant clones were evaluated for replication in the lungs and nasal turbinates of hamsters. Each virus appeared to be attenuated; genetic stability correlated with the level of viral replication in the hamster lung, i.e., viruses which grew best showed a tendency to revert to the ts+ phenotype. Characterization of the ts+ revertants for the presence of the cold adaptation property revealed that these viruses exhibited a spectrum of cold adaptation properties. Two viruses, PI-7 (the parental cold variant) and the CR6 recombinant (A/Queensland/6/72) did not revert in either the lungs or nasal turbinates of hamsters.


Potentiation of FMD vaccines with polycationic-nucleic acid complexes.

The effect of various polycations on the immune response potentiated with poly I:C was studied. It was found that low molecular weight polycations had no potentiating effect. Polylysine was ineffective whereas protamine was superior to lysozyme, poly-arginine, poly-histidine, DEAE-Dextran and histone. A foot-and-mouth disease trivalent vaccine composed of strains A24 Cruzeiro, O1 Caseros and C2 Resende elicited no immune response in swine when adjuvanted with aluminium hydroxide but was effective when emulsified in oil. In general, the immune response was potentiated ten-fold when the emulsion contained poly I:C. The antibody production was in most cases further potentiated by a factor of ten when the nucleic acid double-strand was complexed with 1 : 10 (w/w) DEAE-Dextran. Protamine was as effective, or perhaps even more, than DEAE-Dextran to this effect. Guinea pigs vaccinated with a water-in-oil emulsion type monovalent C3 vaccine showed an increase in antibody production when the vaccine contained poly I:C or poly I:C complexed with 1 : 10 (w/w) protamine.


[Changes in the blood vessels of the spinal cord and spinal ganglia following chronic stimulation of the lumbar regions of the sympathetic trunks and gangliosympathectomy].

Morphological studies in 40 rabbits demonstrated that chronic irritation of the lumbar sympathetic trunks resulted in more pronounced architectonic changes, in vessel walls and in neurons of the lumbar sympathetic ganglia in 15 days than did the bilateral lumbar gangliosympathectomy at the same time. In both series of experiments more prominent changes were noticed in the spinal ganglia than in the spinal cord, that could be explained by different degree of lesions in the nerves supplying them and by organic specification of their angioarchitectonics. The data obtained made it possible to include novocain block (anesthesia) into complex therapy to manage spinal apoplexy in clinic.


[Detection of enterochromaffin cells by the luminescence method with lighting from the side].

A method is suggested to detect luminescence of enterochromaffin cells of the intestinal tract after a routine fixation of sections in 10% formalin, imbedding in paraffin, and examination under the microscope when the light is directed to the preparation laterally, at the angle of 30--40 degrees. The sections fixed on the glass are deparaffined (xyline, chloroform), dried quickly in the air until "bleaching" and mounted in vaseline oil. Under a light microscope, with lateral illumination of the preparation, enterochromaffin cells have golden yellow luminescence. This simple method makes it possible to study enterochromaffin cells in stained preparations and can be useful for cytofluorometric studies.


[Assembly organization of the motor region of the cerebral cortex in adult humans].

Field IV and adjacent areas of fields VI, VI op, VI p of the human brain cortex were examined. Frontal, sagittal, tangential sections stained after the techniques of Nissle, Brachet, Klüver--Barer, Cajal and Peters demonstrated the motor cortex to contain a great number of local, with rare overlapping, groups of cellular columns, each of them being surrounded with a peculiar vessel-fibrillar capsule. A morphological unit resulted from topographic interdependens of neurons, vessels and fibres is considered as a neuronal assembly which occupies in the cortical space a figure of truncated upset cone or cylinder. Neuronal assemblies are distributed along radiate fibres and radial vessels, do not form regularly alternated raws, central axis of every assembly is perpendicular to the tangent line drawn in the given point of the cortical surface.


[Quantitative characteristics of ultrastructural changes in axo-dendritic synapses under the influence of tetanus toxin].

Changes in synaptic ultrastructure of the external geniculate body (EGB) were investigated in rats when a generator of pathologically intensified excitation (GPIE) was produced in this nucleus under the influence of tetanus toxin (TT). At the period of pronounced convulsive activity (24 h after TT injection), synaptic changes were estimated electronmicroscopically and with quantitative comparison of the materials from three groups. The first group included EGB synapses where TT was injected, the second group included contralateral EGB synapses and the third included EGB from the rats injected with inactivated toxin. By means of electron optic computer "Klassimat" average amount of round, flat, anomalous and adjacent to the presynaptic membrane vesicles was measured, average relative length of the active zone, average area of the presynaptic terminal, average relative section areas of pre- and postsynaptic cytoplasm condensation were estimated. In the area of GPIE formation, under the influence of TT, the increased amount of the vesicles related to the presynaptic membrane and that of flat vesicles were statistically significant. At the same time, the synaptic terminals, by the number of vesicles, have bimodal, while the control groups have unimodal distribution.


[Structure of spinal cord capillaries in hypokinesia].

Changes in spatial interrelations of the spinal cord capillaries and motoneurons and capillary ultrastructure were studied under hypokinesia. Spatial interrelations between the capillaries and neurons were not demonstrated to change under hypokinesia. They were estimated by the following parameters: area of neuronal profile field, number of capillaries, their length, distance from the nerve cell body, capillary bed area and index of capillary-neuronal interrelations. Quantitative investigation revealed capillary stenosis: their diameter was one and a half times less under hypokinesia. Morphologically, capillary stenosis was accompanied by the basal membrane thickening and endothelial cytoplasm vacuolization. There was a direct relation between endothelial villi and the places of the endothelial cells contacts, dilatation of the contact interstices and solidifying of their borders. Changes in the capillaries were followed by reactions in the pericapillary structures, such as: fibrillae were formed, mitochondrii accumulated in the perivascular glial projections, the membrane next to capillary astrocyte projections underwent desmosome-like condensation. Mitochondrial accumulations were also observed in the nerve cell projections and in their cytoplasm sites contacting with the blood vessels.


[Organization of retinal and lateral geniculate body connections with the hypothalamus in cats].

In order to clarify connective relations between the optic system and activating formations, the pathways from the retina and the external geniculate body to the hypothalamus were investigated in the cat. Methods of Fink--Heimer and of I. V. Victorov were applied. The retina and the dorsal nucleus of the external geniculate body were stated to have efferent connections with the same nuclei in the anterior hypothalamus. Medial and posterior hypothalamus do not accept such connections. Retino-hypothalamic and geniculate hypothalamic pathways are demonstrated to terminate in the supraoptic and suprachiasmic nuclei. These pathways are bilateral and quantitatively equivalent.


[Structural basis of frontal cortex control of thalamic and basal nuclei in dogs].

Fibrillar degeneration after extirpation of the frontal cortical field F2, central part, was observed in dogs by Nauta--Gygax and Fink--Heimer's methods. Degenerated fibrillae were stated to form two bundles and terminate near the neurons of nonspecific thalamic nuclei: n. ret, MD, pf, sprf, as well as in the neurons of specific thalamic nuclei: n. Vna, cgl, cgm, pul. Degenerated processes of the frontal cortex cells projected to the neurons of basal nuclei: the head of nucleus caudatus, putamen, globus pallidus. In the claustrum degenerative changes were not observed.


[Ultrastructure of the central nucleus of the inferior colliculus of the cat midbrain].

Ultrastructure of the central nucleus in the cat posterior colliculus was studied (cells, fibres, synaptic architectonics). Three types of amyelinated fibres were determined: with great number of mitochondria, with usual number of mitochondria, with large amount of granulated vesicles. The results obtained were compared with the data of electron microscopic study of the inferior geniculate body, as they are subcortical formations belonging to the same auditory system but differentiating in their functions. Possible physiological interpretations of the results are considered.


[Afferent pathway from locus coeruleus to the nucleus solitarius].

After the destruction of the nucleus tractas solitarii, just caudally to the writing pen by means of a stereotaxic instrument, the system of afferent fibres to the nucleus in question was investigated by the methods of Nauta and Fink--Heimer. The fibre terminals were revealed near locus coeruleus. Investigation of the locus coeruleus by Golgi method demonstrated that it usually has neurons of reticular type and transitional ones which resemble by their form the neurons specific for sensory formations. It is possible to conclude that locus coeruleus posesses connections of visceral origin which may play a part in the afferent influence of locus coeruleus on the brain cortex.


[Thalamo-amygdalar connections in the cat brain].

Afferent connections of the cat amygdalar nuclei with the thalamic structures were studied by Nauta's method; simultaneously, geometrical features of the afferent fibres in amygdala were investigated by Golgi's method and its synaptic architectonics was examined by Golgi--Deineka's method. No pathways were demonstrated from the medial line nuclei (paraventricular, interanteromedial, rhomboid, central medial and reunial), from intralaminar nuclei (central lateral, paracentral and parafascicular) and from the lateral part of the thalamic medio-dorsal nucleus to the amygdala. From the medial part of the thalamic medio-dorsal nucleus into the basal-lateral nuclei of the amygdala (mainly into the large cells of the basal nucleus) come a great number of lemnisc-like fibres which form at the end a thick brush from very fine fibrillae having beady thickenings and connected with the neuronal dendrites of the amygdala.


[Characteristics of neural connections and capillary networks in field 17 of the cerebral cortex in rabbits and cats].

Some structural-functional relations in the analyzer's optic nucleus and adjacent associative fields were investigated comparing it with the cortical limbic area in the rabbit and cat. New approaches for the structural brain cortex analysis were applied: method of retrograde elective detection of cortical and subcortical neurons (with the body and dendritic processes) after surgical lesion of their axons in the cortical focus of destruction, field 17. This method demonstrated the presence, in the fields surrounding the cortical optic nucleus, of associative neurons mediating the modal signals into the nucleus of the optical analyzer, as well as some constructive details of the optical analyzer at the subcortical level. Comparing angioarchitectonics of the capillary network, indirect data were obtained on structural-functional specialization of the nucleus of the optical analyzer, that explains the meaning of mediating into it the optical signals which come to other cortical areas (from the zone of scattered elements).


[Dynamics of protein concentration in the neurons of a chronic "mirror" epileptiform focus].

Protein content in the neurons of layers III and V in the rat brain anterior-parietal cortex and the lateral thalamic nucleus was studied 11 and 63 days after cobalt implantation. In the course of the experiment, protein content increased by 44--49% in the neurons of layer III and decreased by 24--32% in the thalamic neurons. In small and large pyramids of layer V, protein content decreased by 21--28%, 11 days after cobalt implantation, and approached normal content by the 63rd day. It was concluded that according to morpho-functional characteristic of certain neuronal types (associative, in layer III, predominantly efferent, in layer V and associative neurons in subcortical formations of the lateral thalamic nucleus) their protein changes in response to convulsive activity were different.


[Characteristics of the follicular epithelium in the fishes with demersal roe. Concerning the classification of unilaminate monomorphous follicular epithelium of the vertebrates].

Follicular epithelium of  Hemichromis during the periods of small and slow oocyte growth changes from flattened prismatic into high prismatic; during the periods of fast oocyte growth, the follicular epithelial cells undergo secretory specialization. Secretion is of apocrine type and forms the second oocyte tunica. According to the literature data analyzed and the author's investigation, in the development of unilaminate monomorphous follicular epithelii, it should be distinguished: a) period of primary transformation with characteristic intensive proliferation of epithelial cells, their morphologic transformation, upward growth of epithelium and increase of its physiological activity; b) period of secondary transformation either at the expense of secondary follicular epithelial flattening, or by means of secretory specialization of its cells. It is suggested to name unilaminate monomorphous follicular epithelii in vertebrates according to their construction at the end of the primary and by the character of the secondary transformation. Thus, follicular epithelium of Hemichromis can be defined as highly prismatic with secondary specialization.


[Dermal and intestinal epithelium of the Enteropneusta as a phylogenetic stage of development of the Chordata].

A comparative histological investigation of dermal and intestinal epithelium was made in Saccoglossus mereschkowskii (Enteropneusta). Nucleic acids (Feulgen reaction), glycogen (PAS-reaction, Best's staining), mucous (mucicarmine), total proteins (xanthoprotein reaction), neutral mucopolisaccharides (PAS-reaction) were determined histochemically. The dermal and infestinal epithelia of S. mereschkowskii have false pseudostratified composition and consist of ciliary and glandular cells. Peculiar "giant" cells with phagocytosis as their main function are also found in the intestinal epithelium. Ciliary cells of the intestinal epithelium are capable for secreting. A comparison between the dermal and intestinal epithelii is presented in the article. A supposition is made on the primitive structure of false pseudostratified composition of the dermal and intestinal epithelii. The epithelia of Enteropneusta are considered as an initial developmental stage of dermal and intestinal epithelia in phylogenic line of Hemichodata-Chordata.


[Histophysiological analysis of adaptation of ecologically different species of sturgeons to hypertonic medium].

In saplings of Acipensar güldenstädti Brandt while adapting to sea water with salinity of 12.5%, the main functional changes in the chloride cells of the branchiae, the thyroid gland and interrenal tissue occur within the first 12 hours. During this period, concentration of osmotically active substances in blood serum increases (the first stage). Adaptive decrease of this concentration (the second stage) takes place after activation of the endocrine glands and transition of the chloride cells into excretory state that stipulates, in fact, the change of osmoregulatory type in fish for the transition from fresh water into hypertonic medium. After activation, the endocrine glands return to moderately active state. Adaptation of Acipenser baeri stenorrhynchus var. baicalensis to sea water with salinity of 12.1% produces isoosmotic changes in blood serum to the external medium.


[Development of the nasal cavity and formation of the nostrils in human embryogenesis].

The development of nasal cavity was traced in human embryos. The identity in the primitive formation of the mouth cavity and that of the nasal cavity is stated. During embryogenesis, the primitive nasal cavities are demonstrated to change their position concerning the mouth cavity. Epithelial "cluster" formation in the area of the nostrils is examined: it appears in embryos of 16-19 mm long, is mostly prominent in embryos of 50-55 mm long, is absent in fetuses of 5.5 months old. By comparing the terms and dynamics in the development of epithelial adhesion in the larynx an the nostrils, the importance of these temporal structures for protecting the respiratory tract of the embryo from amniotic fluid is demonstrated.


[Topography and cytoarchitectonics of the main cortical zones of the turtle forebrain].

The description of cytoarchitectonics and topography of the three principle cortical zones of the forebrain of Emys orbicularis reveals that the cortical structures in the species are precisely distinguished with respect to their neuronal characteristics, density and the situation of cellular elements. Emys orbicularis occupies an intermediate position among the species of the order Chelonia described in the literature as regards the level of development of the forebrain cellular structures. Emys orbicularis is less progressive in respect to the structure of telencephalic cortical formations than Testudo carolina and has a number of progressive properties as compared with Testudo geometrica. Testudo graeca seems to be close to Emys orbicularis in the development of forebrain cellular structures.


[Characteristics of the ovum cleavage and the importance of the preblastula phase in the embryogenesis of the Nematoda].

The figure of tetrahedron is formed in certain species of Plectus and in Tobrilus gracilis at the stage of 4 blastomeres rather than a rhombus which is formed in most highly organized nematodes. The analysis of the Nematoda's embryogenesis allows to conclude that tetrahedron, rhombus as well as some other figures play the role of preblastula sustaining the most expedient disposition of the first blastomers for transition to the formation of the blastula. With the increasing organization of nematodas the tetrahedron preblastula turns into a rhombic, linear-rhombic and at last in aphelenchoid-tylenchoid one. The character of the distribution of structural elements of organs and tissues of the definitive animal in the cytoplasm of the egg of Plectus and Tobrilus confirms the rightness of the division of the class of nematodas into subclasses Enoplia and Chromadoria rather than subclasses Adenophorea and Secernentea.


[Carpal bones of the Chiroptera in the comparative-anatomical and functional aspects].

Data on investigation of hand sceletal bones carried out in eight genera of three families of bats were subjected to comparative-anatomical and functional analysis. Quantitatively, the hand sceletal bones of Chiroptera preserve constructive pattern general for the hand of terrestrial mammalians Pentadactilus. It has rudiments of the prefirst (Pp) and the seventh (Pm) rays. The latter is situated on the volar surface of the base Mc5. Scaphoid, semilunar and central carnal bones of Chiroptera, like those of Mototremata, some Marsupialia, Insectivorona and Carnivora merge together into one large bone--os lunatum. At the same time, the hand of Chiropter is a highly specialized structure, that is evident from the presence of articular restricotrs of anterior sagging of the wrist, crests and grooves directing movements in a strictly definite plane, from fan-like spreading and bringing together the rays, from very long metacarpal bones and proximal phalanges, from reduction of distal phalangs of the 3d and 5th fingers. Thus, the hand of Chiroptera is a unique example of combination of primitive, initial for pentadactule plantigrades wrist with signs of narrow specialization resembling, to some extent, those of Ungulata; only in Ungulata those signs developed on the base of digitigrades wrist.


Sepsis rates in hip replacement surgery with special reference to the use of ultra clean air.

A study is reported of sepsis rates in 836 total hip replacements carried out in various physical environments including ultra-clean air. In a further sutdy the bacteriology of the air around the wound and of the wound itself was investigated during the course of 32 joint replacement operations with and without ultra-clean air. Bacteriological contamination of the air was markedly reduced by the use of ultra-clean air but the wounds themselves were no cleaner than with conventional air conditioning provided that unsterile personel were kept at least Imetri away from the sterile area. The sepsis rate was high at the outset of the study (when a physically apalling theatre was in use, the operative technique was novel and prophylactic antibiotics were not employed). Thereafter it fell and remained unchanged in spite of the introduction of ultra-clean air. We conclude that the efficacy of techniques amiced at sterilizing the air around the wound may now be unprovable in view of the low sepsis rates which can be obtained in a conventional environment. Our results do however show that unsterile personel should not be allowed to approach within Imetri of the sterile area, whatever venitlation is employed.


[Comparative experimental investigations with bioglass (L. L. Hench), Al2O3-ceramic and Al2O3-ceramic coated with a mod. Bioglass. I. Results of experiments under non-loaded conditions (author's transl)].

This report deals with comparative results obtained with unloaded intra-osseous implants of bioglass (L. L. Hench), Al2O3-ceramic and Al2O3-ceramic coated with a mod. bioglass. Al2O3-ceramic and bone form a direct bony interface without fibrous tissue interposition, this resulting in a pure mechanic fixation of the implant through frictional forces of the surface roughed ceramic. Pure bioglass (45S5) and bone form a unique persisting direct interface by means of physico-chemical or biochemical phaenomena stabilizing the implant. Interface stability seams to be higher than the fatique strenth of the glass itself. This interface is developed as a consequence of solubility of some of the glass constituents within a surface layer of up to 200 microns, running parallel with a reduction of strength of this surface glass layer. The boronoxide containing bioglass, flame-sprayed onto Al2O3-ceramic samples seams to be less soluble and therefore seams to have lesser bonding capability to bone. The stability of the interface bioglass coating-Al2O3-ceramic was low.


[The lateral tension band--a method of osteosynthesis of patella fractures for immediate carrying capacity (author's transl)].

The tensions caused by means of flexors and tensors on the intact and by various procedures operated fractured patella have been determined. The disadvantages of the cerclage and the eccentric ventral tension band, both of them mainly usual, are exposed. Interfragmentary measurements of pression power in a corpse knee as well as breaking tests with a model patella and first experiences by operation with a new method confirm the reflexions. Principles for a modus of osteosynthesis for fractures of the patella are realized by the lateral tension-band. All loading inclined fragment distractive powers thereby are taken up by production a high-level interfragmentary compression, so that immediate postoperative loading is possible.


[Disordered fibrillar structure in ruptured tendons (author's transl)].

Areas of disordered fibrillar structure similar to kinking deformities have been observed in specimens from ruptured tendons. It seems possible to compare this phenomenon with experimentally produced deformations. The significance for the pathomechanics of tendon rupture is discussed.


Experi-mental: a simulation of the distribution of services to mentally deficient children.

In this study a formal analytical technique was introduced in typical planning operation of the Quebec Ministry of Social Affairs. The mental deficiency sector of the province was chosen because important changes were imminent in both the orientation and types of services provided to children in this sector. A simulation model was constructed according to system dynamics methodology to provide an integrated description of the social impact of these changes. The immediate result of the simulation model was to focus a reevaluation by government planners on certain operational features of the system of services and the implementation schedule of the ministry's policy. In a broader context, the model demonstrated that simulation is a viable approach to planning social services. Similar social services studies have been initiated to familiarize government planners with the methodology and have been used in the preparation of precise implementation plans.


Studies on the pathogenesis of ischemic cell injury XV. Reversal of ischemic cell injury in hamster trachea and human bronchus by explant culture.

Hamster tracheal epithelium survived 3 hours of total ischemia at 37 degrees C as demonstrated by its ability to be maintained in organ culture for 7 days subsequent to the ischemic episode. Epithelium ischemic for longer periods did not survive in culture. Human bronchial epithelium obtained from surgically resected lungs showed the acute effects of ischemia, i.e., the cells had dilated endoplasmic reticulum and swollen mitochondria. These cellular effects of ischemia were, however, reversed by placing the bronchus in explant culture. Bronchus obtained at autopsy, 2 to 3 hours following death, showed epithelial cells suffering severe ischemic cell injury, most of which did not survive in culture, but in some cases, a few basal cells survived to form a non-keratinizing squamous epithelium.


Morphology of mouse epidermal cells in vitro: a scanning electron microscopy study.

Scanning electron microscopy of isolated epidermal cells from newborn mice grown in vitro showed that the cultures consisted of several morphologically different types of cells. Young cultures had many smooth, round cells while older cultures contained more cells with rough or ruffled surface and a varying number of flat, irregular cells. Probably, the various cell types corresponded to different stages of differentation (keratinization). Cultures that were grown in the presence of retinyl acetate (12.5 microgram/ml) had more round and smooth cells after several days in vitro than the controls. This could indicate that retinyl acetate delayed or altered cell differentiation. Scanning electron microscopy of the cultures consistently showed that the cells were situated at different layers. The apparent monolayer seen by phase contrast microscopy therefore seems to be an optical phenomenon due to projection of the cells onto the same plane.


In vitro effects of Cytochalasin B on TA3 tumor cells.

We studied the effect of Cytochalasin B (CB) on two lines of the ascites tumor TA3 by microcinematography and scanning electron microscopy. CB induces a dose dependent and reversible cell paralysis. One microgram CB/ml causes a pronounced but incomplete paralysis. The cells retain their general shape but develop numerous blebs. Ten microgram CB/ml causes a complete cell paralysis and a retraction of pseudopods and microvilli. When CB is removed, the cells rapidly regain their original form and motility. The recovery process starts within minutes after CB removal and is almost completed in 15 min.


[Oncorna-like virus particles in the cochlear spiral ganglion of guinea pigs (author's transl)].

Virus particles in spiral ganglion cells of the guinea pig have been grouped with herpes viruses. The purpose of this study was to evaluate this classification of the viruses and their influence on cell morphology. 20 healthy, adult guinea pigs from different breeds were studied. The spiral ganglion was serially sectioned and examined electron micoscopically. All examined spiral ganglions of several guinea pig populations from different breeds showed intracytoplasmic viruses in some granular spiral ganglion cells. According to their localization and morphology we classify these viruses with the oncorna virus group. This is not in agreement with the classification of other authors. Apparently there is a world-wide latent viral infection in guinea pigs. The accumulation of lysosomal-like vacuoles in vicinity to the viruses indicates an increased local lysosomal activity of the infected ganglion cells. Considering the otherwise normal ultrastructure of the infected cells an additional influence of these viruses on the intracellular metabolism can neither be demonstrated nor denied.


Occurrence of myofibroblasts in the different phases of morbus Dupuytren (Dupuytren's contracture).

Twenty-one surgically removed specimens of Morbus Dupuytren (M. D.) were studied by light and electron microscopy. The cell type observed in the proliferative phase shows the basic ultrastructural features of fibroblasts, while the majority of the cells in the involutional phase resemble myofibroblasts. Myofibroblasts exhibit ultrastructural characteristics of both smooth muscle cells and fibroblasts and are said to behave functionally like smooth muscle cells. In the residual phase, typical fibrocytes of connective tissue are found. These findings confirm the concept that fibroblasts are capable of converting into myofibroblasts and demonstrate the myofibroblasts represent an intermediate cell type of transitional cellular differentiation. The significance of myofibroblasts for the development of the contracture of M. D. is discussed.


Intracellular "fibrous long spacing" collagen in morbus dupuytren (Dupuytren's contracture).

Fine structural analysis of 21 surgically removed specimens of Morbus Dupuytren (Dupuytren's contracture) in the cells of the proliferative phase revealed spindle-shaped or round, periodic banded structures of 1--1.5 micron size. These intracellular structures are surrounded by trilaminar membranes of 45 A continuous with membranes of the endoplasmic reticulum. The periodic banded structures display a light-dark pattern of 750--900 A and resemble with respect to periodicity and general morphology "fibrous long spacing" collagen. To date, "fibrous long spacing" collagen in human tissue has only been observed in the extracellular space, both in normal and pathologic conditions. Its formal pathogenesis is discussed.


Rheumatoid disease with involvement of the leptomeninges presenting as symptomatic epilepsy.

A case of rheumatoid disease with localised granulomatous involvement of the leptomeninges is described. This meningeal disease apparently caused a symptomatic epilepsy. This is thought to be only the second reported case of rheumatoid granulomatous involvement of the leptomeninges.


[On the diagnosis of colorectal polyps (author's transl)].

After colorectal polypectomy the further surgical therapy is based upon histomorphological features. In case of an adenoma with carcinoma, statements concerning classification, degree of differentiation (grade of malignancy), and depth of invasion are necessary. For the histopathological report a form is recommended. When completing this form all clinically essential informations are given.


Effect of vitamin A nutritional status on the ribonucleic acids of liver, intestinal mucosa and testes of rats.

1. Vitamin A deficiency led to an increase in the oligonucleotide fraction of testes and intestinal mucosa of rats at the expense of high-molecular-weight RNA and 4S RNA, but no such changes were observed in the liver. Retinyl acetate supplementation reversed these effects in both tissues, whereas retinoic acid supplementation was almost equally effective in the mucosa but virtually ineffective in the testes. The ribonuclease activities of all the tissues remained unaffected by the above treatments. 2. The effect of vitamin A deprivation on the acceptor activity of the tRNA of the testes and intestinal mucosa was more pronounced than on the liver tRNA. The testes and mucosal tRNA of the retinoic acid-supplemented rats showed significantly lower charging capacity as compared with the retinyl acetate-supplemented ones. Here also no significant effect was observed on the liver tRNA. 3. Vitamin A deficiency caused a decrease in the percentage of poly(A) in RNA of the mucosa and testes, but not in the liver RNA. The poly(A) contents of both tissues were brought to normal by retinyl acetate supplementation; treatment with retinoic acid led to an appreciable increase in poly(A) in the mucosa, but considerably less increase in poly(A) in the testes. 4. The incorporation of H332PO4 into the rRNA and tRNA of the testes was lowered by vitamin A deficiency, but no such effects was observed in the liver RNA.


Iron-sulphur centres in mitochondria from Arum maculatum spadix with very high rates of cyanide-resistant respiration.

X-band electron-paramagnetic-resonance spectroscopy at 4.2--77K combined with measurements of oxidation-reduction potential was used to identify iron--sulphur centres in Arum maculatum (cuckoo-pint) mitochondria. In the oxidized state a signal with a derivative maximum at g = 2.02 was assigned to succinate dehydrogenase centre S-3. Unreduced particles showed additional signals at g = 2.04 and 1.98 (at 9.2 GHz), which may be due to a spin-spin interaction. In the reduced state a prominent signal at g = 1.93 and 2.02 was resolved into at least three components that could be assigned to centres S-1 and S-2 of succinate dehydrogenase (midpoint potentials -7 and -240 mV respectively at pH 7.2) and a small amount of centre N-1b (e'o= -240 mV) of NADH-ubiquinone reductase. In addition, changes in line shape around -10 mV indicated the presence of a fourth component in this signal. The latter was more readily reduced by NADH than by succinate, suggesting that it might be associated with the external NADH dehydrogenase. The iron-sulphur centres of NADH-ubiquinone reductase were present in an unusually low concentration, indicating that the alternative, non-phosphorylating, NADH dehydrogenase containing a low number of iron-sulphur centres may be responsible for most of the high rate of oxidation of NADH.