Containment of hepatitis B virus infection in a hemodialysis unit. The unsuspected introduction of a carrier of hepatitis B virus into a hepatitis-free hemodialysis unit coincided with a routine serologic survey in early April 1976. Thus the prevalence of hepatitis B surface antigen and its antibody was known for the 42 patients and 23 personnel at risk. Control consisted of isolating the patient identified as a carrier seven days after admission. Immune globulin was not given to potentially exposed persons. During a 15-month period, only one case of icteric hepatitis B occurred, in a nurse who was probably infected through defective gloves while attending the carrier in isolation. Monthy serologic tests showed that none of the other personnel and patients became infected with hepatitis B virus. This limited spread of hepatitis B indicated that isolation of the carrier was an effective preventive measure in given setting.


Carotenoid pigments and the treatment of erythropoietic protoporphyria. Carotenoid pigments protect photosynthetic organisms against photosensitization by their own chlorophyll. This photoprotective function of carotenoids was utilized in the treatment of a human photosensitivity disease, erythropoietic protoporphyria.


Paraquat-induced changes in the rate of collagen biosynthesis by rat lung explants. Paraquat, bipyridilium herbicide know to cause pulmonary fibrosis, was injected IP into rats. The rate of synthesis of collagen by lung minces from these and control rats was evaluated by measuring the rate of synthesis of hydroxyproline, a specific marker for collagen in lung. Synthesis was measured by incubating lung minces with radioactive proline for various amounts of time, after which proline specific activity and labeled hydroxyproline were determined. The size of the proline pool within the lung minces was significantly elevated in minces from rats that had been injected with paraquat, thus causing the specific activity of the [3H]proline precursor to be lower in these lungs than in those from control animals. Lung minces from rats administered paraquat made more collagen than did those from uninjected controls. The actual increase in rate of collagen synthesis correlated well with other independent estimates of paraquat-induced damage to the lungs.


In vitro assessment of interaction of blood with model surfaces. An in vitro system for the assessment of blood compatibility of artificial surfaces is described. Anticoagulated human whole blood was pumped through columns of beads and then analyzed for evidence of platelet retention and the release of platelet constitutents. Platelets were retained on the columns by adhesion to the beads and by aggregation. Experiments were conducted with PVAc, PC, PMA and PS beads to provide data on the reproducibility of the system and the effects of anticoagulants and RBC concentration on platelet adhesion and release. The system is versatile, inexpensive, reproducibile, and also suitable for studies of the effects of pharmacologic agents and other aspects of platelet-artificial surface interaction.


Inhibitors of erythroid colony-forming cells (CFU-E and BFU-E) in sera of azotemic patients with anemia of renal disease. A number of potentially toxic compounds accumulate in the sera of patients with end-stage renal disease, and some have been demonstrated to inhibit erythropoiesis. In vitro CFU-E and BFU-E erythroid colony growth was compared in the presence of sera from patients with anemia of renal insufficiency and normal human subjects with the use of plasma clot cultures of normal rabbit bone marrows. In studies of sera from nine undialyzed patients with anemia of renal insufficiency and seven normal human subjects, all undialyzed sera from the anemic uremic patients produced a significant (p less than 0.001) inhibition of both CFU-E and BFU-E. A marked reduction in the inhibitor of CFU-E was seen in the sera of three out of four patients following intermittent hemodialysis. Creatinine, guanidine hydrochloride, guanidinosuccinic acid, and guanidinobutyric acid did not affect the number of CFU-E in normal rabbit bone marrow cultures. These data suggest that uremic toxins in the sera of undialyzed anemic uremic patients inhibit erythropoiesis, are partially removed by regular hemodialysis, and may play an important role in the mechanism of the anemia associated with renal insufficiency. These inhibitors of CFU-E do not appear to be creatinine or guanidine derivatives.


Kidney metabolism of acetaminophen and phenacetin. The metabolism of acetaminophen and phenacetin by rabbit kidney slices was investigated. Phenacetin, like aspirin, inhibited [131I] Hippuran accumulation by the organic acid transport system. Phenacetin exhibited a dose-dependent inhibition with a K1 of 0.5 mM; acetaminophen at concentrations as high as 1 mM did not alter organic acid transport. [3H] acetaminophen slice: media ratios of approximately 1 or less suggested that acetaminophen entered cortex and outer and inner medullary slices by diffusion rather than active transport. Approximately 95% of the acetaminophen within the slices readily diffused out into the media. The chromatographic patterns of this material were similar to that of the incubation media. The acetaminophen remaining within the slices was acid-precipitable and not extractable with organic solvents. This covalent binding of acetaminophen was inhibited by glutathione. More acetaminophen was bound in the renal medullar than cortex. These data suggest that the renal metabolism of acetaminophen observed in this in vitro study may be related to the nephritis observed in analgesic abuse.


Stability of hemoglobin solution during extended storage. Hemoglobin solution, proposed as a blood substitute, must be stable for a long period of time in order to be stockpiled and be readily available when massive clinical transfusions are required. Hemoglobin solutions, prepared by crystallization and maintained in blood bags under sterile conditions, were stored at -20 degrees, 4 degrees, and 25 degrees C. At several intervals, methemoglobin content, p50, n values, osmolality, oxygen capacity, Na, K, and pH were assayed. Solutions maintained at -20 degrees C demonstrated no alterations in these parameters after 2 years of storage. Solutions kept at 4 degrees C remained stable for 12 months. After 12 months and especially after 18 months, deterioration was evident inthe refrigerator-stored solutions, as demonstrated by an increase in methemoglobin content and a decrease in P50. Attempts to store hemoglobin in liquid form at room temperature without alterations in structure and function of hemoglobin were unsuccessful. The characteristics of hemoglobin prepared from fresh or outdated blood were essentially the same.


Menopausal changes in calcium balance performance. Calcium balance as a function of both intake and absorption of calcium fromthe diet was measured 274 times in 168 normal perimenopausal women, and comparisons made between groups of women segregated according to menopausal and estrogen therapy status. As previously reported, there is a statistically significant positive correlation between calcium balance and both calcium intake and calcium absorption. In 207 studies in premenopausal women calcium balance averaged -0.0199 gm/day, whereas in 41 studies in postmenopausal women untreated with estrogen, calcium balance averaged -0.043 gm/day (p less than 0.02). The balance difference was due approximately equally to decreased absorption from the diet and to increased urinary excretion. Twenty-six estrogen-treated postmenopausal women exhibited balance performance indistinguishable from that of the premenopausal group. In 16 women who were studied twice, 5 years apart, and who went through menopause between studies, calcium balance shifted by -0.0307 gm/day (p less than 0.05) as compared with 72 women also studied twice, but without change in menstrual status, in whom mean balance did not change significantly. Calcium intake requirement for zero balance was calculated for both the estrogen-replete and estrogen-deprived groups. Premenopausal and treated postmenopausal women exhibited an intake requirement of 0.990 gm/day Ca, whereas the untreated postmenopausal women had an apparent requirement of 1.504 gm/day (p less than 0.01). We conclude that there is a specific, estrogen-related shift in calcium performance across menopause and that the reason for the positive effect of estrogen on balance and intake requirement is a combination of enhancement of intestinal absorption efficiency and improved renal calcium conservation.


Menopausal changes in bone remodeling.

Menopausal changes in bone remodeling. Bone remodeling was measured by a calcium-kinetic method in 151 normal perimenopausal women, and the effect of estrogen status on remodeling level and skeletal balance was determined. Premenopausal women exhibited remodeling rates of 0.337 gm/day Ca for mineral accretion and 0.358 gm/day Ca for mineral resorption. The difference between the two rates (computed skeletal balance) was -0.021 gm/day Ca. Postmenopausal women treated with estrogen in a mean dose of 0.0188 mg equivalents of ethinyl estradiol exhibited values for accretion and resorption (0.332 and 0.351 gm/day Ca), essentially identical with those of the premenopausal group. However, untreated postmenopausal women exhibited remodeling rates of 0.387 gm/day Ca for accretion and 0.425 gm/day Ca for resorption, with a computed skeletal balance of -0.038 gm/day Ca. These values were significantly higher than those of either the premenopausal or treated postmenopausal groups. Paired studies across menopause in 15 of the women demonstrated a rise in remodeling rates virtually identical to that estimated from the differences between groups. Estrogen loss at menopause is thus associated with an apparent partial release from an inhibition of skeletal resorption, and this release is, in whole or part, responsible for the negative skeletal balance shift associated with the postmenopausal years.


Temperature cycling preserves platelet shape and enhances in vitro test scores during storage at 4 degrees. Platelets stored at 4 degrees develop morphological changes which precede decreases in in vitro aggregation and recovery from hypotonic shock. Platelets maintained at 4 degrees for 60 min lack microtubules and lose their discoid shape as a result of the formation of pseudopodia. Exposure to continuous cold for 24 hr causes irreversible platelet shape changes and induces spontaneous aggregation. Quantitative electron microscopic analysis of platelet microtubules showed that platelets lost their ability to reassemble microtubules after 24 hr of continuous storage at 4 degrees. However, interruption of continuous cold storage with short, repeated pulses of 37 degrees (temperature cycling) extended microtubule reassembly capabilities for 72 hr and maintained platelet shape change capabilities. A comparison of platelets stored continuously at 4 degrees with those stored by temperature cycling showed that temperature-cycled platelets possessed improved aggregation responses and significantly improved recoveries from hypotonic shock. These data indicate that 37 degrees reactivation pulses during cold storage provide platelets with markedly improved morphology and in vitro test scores and suggest that temperature cycling may be used to extend blood bank storage of platelets.


Modulation of granulopoiesis: opposing roles of prostaglandins F and E. CSF-dependent myeloid colony growth can be augmented or inhibited by a number of modulating factors. PGs of the E series are known to inhibit colony formation. The antagonistic actions of PGE and PGF in many biological systems prompted us to compare their effects on myelopoiesis in vitro. PGF2alpha at an optimal concentration of 1 x 10(-9)M increased colony formation by 50% over that stimulated by CSF alone. Similar augmentation was also observed from 16,16-dimethyl PGF2alpha, PGF1alpha, 6-keto PGF1alpha, and MIX. In contrast PGE1, PGE2, and 15(S),15-methyl PGE1 inhibited colony growth. Simulation by PGF reflected an absolute increase in granulocytic colonies, whereas inhibition by PGE affected both granulocyte and macrophage colony formation. The relative levels of PGE and PGF may play a determining role in the modulation of granulopoiesis.


Experimental radiation pneumonitis: changes in physiology of the alveolar surface. Mice received 2400 rads in two fractions to the thorax; 4 months later at a time when deaths began, mechanical and biochemical properties of the lungs were studied and compared to those of littermate controls. The principal mechanical change was a large increase in the elastance of the alveolar surface element and abnormal surface tension properties of the AF. Alveolar fluid phospholipid content and saturation were only minimally change; however the alveolar fluid contained a large excess of protein, possibly of circulatory origin. The latter may explain the fall in compliance of the alveolar surface and hence of the lung in radiation pneumonitis. A small increase in elastance of the lung tissue element was also found; this correlated with a decrease in lung volume and a small increase in lung hydroxyproline content. These changes may signify the early development of radiation fibrosis. Other features of this model are the frequent occurrence of pleural effusions and the presence of increased numbers of alveolar macrophages in the alveolar lavage.


Mucocele of the paranasal sinuses. A retrospective clinical and histological study. Clinical and radiological findings in 112 patients with muco/pyocele in the paranasal sinuses are presented. The modified Lynch-Howarth operation gave a primary cure rate of 82% which is satisfactory compared with other reports. Histological examination of the mucocele membranes and anamnestic information support the theory that a mucocele develops secondary to obstruction of the sinus outlet.


Radiographic diagnosis of foreign bodies in the oesophagus. In a group of patients suspected of harbouring a foreign body in the oesophagus, the diagnostic accuracy of radiographic examination is found to be high. Only 1 of 243 patients examined by radiography presented a false negative result.


'Otorrhagia'. A symptom of posterior auricular artery aneurysm. There are many reports regarding aneurysms of the external carotid artery and its branches, but the case presented in this paper, of an aneurysm of the posterior auricular artery, is a unique one.


Agnogenic myeloid metaplasia with ear involvement. A 52-year-old man with agnogenic myeloid metaplasia had a sudden onset of pain and bleeding from the left ear and an associated decrease in hearing acuity on that side. Examination revealed a friable mass that filled the middle ear and protruded through a perforated tympanic membrane. Special staining of a tissue specimen of the mass revealed myeloid metaplasia. Otorhinolaryngologists should be aware of the fact that the ear can be involved in hematopoietic disorders.


Congenital midline sinuses of the dorsum of the nose. Three cases of mid-line dorsal nasal sinuses are reported, together with their mode of surgical management. The embryologic origin of this malformation is discussed, relating their presence to a double fronto-nasal process instead of one.


Ipsilateral absence of tonsil and microtia with ectopic salivary gland. A case report. This case of congenital unilateral absence of the faucial tonsil and microtia, with atresia of the external auditory canal, and an ectopic salivary gland has not been reported previously; it differs from other congenital abnormalities reported earlier.


A massive sublingual--cervical dermoid.

A massive sublingual--cervical dermoid. An unusual case of a massive sublingual-cervical dermoid is presented. The salient features of the condition in relation to its incidence, embryology, pathology, symptomatology and management are discussed.


A systems approach to planning large-scale, integrated health care facilities. This paper presents an overview of a systems approach being implemented within the Kaiser-Permanente Medical Care Program (KPMCP) for the planning of large-scale, integrated health care facilities. This approach was motivated by the increasing change and complexity of factors, both external and internal to KPMCP, that now require more systematic treatment and that before were handled by more intuitive approaches. Among others, these factors include dealing with increasing regulation from government agencies and accommodating the active participation of knowledgeable personnel to ensure the continuation of a progressive and innovative system. Described within, along with more general issues, are various computer models, based upon Kaiser concepts and data that have been developed to facilitate the effective allocation of resources.


An input-output model for resources planning in a medical care system. As medical care delivery systems grow in complexity, the understanding of interaction between entities within the system becomes a key aspect in resource planning. The model presented in this paper is geared to aiding resource planning both at the community or regional level and at the medical facility level. At the regional level the problem is related to the elimination of duplication and the sharing of services. At the medical facility level the concern is the balancing of the supply and demand of services among the departments. The framework of the model is a directed graph with nodes representing the service entities and branches representing the interrelationships. At the regional level, entities are hospitals, clinics, and centralized supportive units, such as the data center or the central laboratory. At the medical center level, entities are generally departments within the facility. An iterative procedure is used to simulate the propagation effect of a change on all entities. The model at the medical center level, as implemented in a minicomputer system was applied to a real problem. The results strongly correlated with another, independent study.


An illustration of the technique of canonical analysis. The use of a multivariate statistical technique, canonical analysis, for the assignment of patients to diagnostic categories is presented. The classification of thyroid status using clinical findings is investigated to exemplify the application of the technique. Emphasis is placed on the stages in the data analysis that are generic in examining any set of medical data for the purpose of automatically classifying patients.


A multivariate data reduction system.

A multivariate data reduction system. The problem of predictive diagnosis based on laboratory data is approached from a mathematical standpoint. A descriptive system is introduced which examines the current information about a clinical problem and identifies best predictors of the problem. Algorithms are described for the assessment of current diagnostic ability, the evaluation of new laboratory tests, and the identification of patients to study for the development of new procedures. The laboratory approach to the predictive diagnosis of iron deficiency is chosen as an example of the system.


Accumulation and depletion of vanadium in selected tissues of rats treated with vanadyl sulfate and sodium orthovanadate. Experiments were conducted to determine the distribution and effects of selected vanadium (V) salts in male rats following continuous ingestion. Wistar rats were continuously fed drinking water ad. Lib. containing 5 and 50 ppm V as vanadyl sulfate and sodium orthovanadate for a 3 month period. At the end of the 3rd, 6th, 9th, and 12th week, blood, kidney, liver, bone, muscle, and digestive tract were collected and analyzed for V utilizing flame atomic absorption spectrophotometry. In addition, the decline of vanadium residues in tissues after 6 weeks of continuous exposure was studied in selected groups. At the 5 and 50 ppm levels, V had no significant effect on body weights or hematocrit values. In the tissues of animals given 5 ppm of V salt, the V contents were essentially the same as those in controls. The tissues of animals given 50 ppm of V salt showed increased levels of vanadium. Kidney had the highest concentration, followed by bone, liver, and muscle. In general, the tissue concentrations of V in animals given 50 ppm as sodium orthovanadate were higher than those exposed to similar levels as vanadyl sulfate. The V concentration in kidney of the animals given 50 ppm sodium orthovanadate continued to rise until the 9th week of sampling, whereas the V content of other tissues analyzed for the treated animals plateaued from the 3rd week. The concentration of V in tissues after cessation of exposure declined rapidly except in the bone. After 6 weeks of the depletion phase the concentration of vanadium in animals given vanadyl sulfate returned to control values except in bone and kidneys. The animals exposed to sodium orthovanadate contained relatively high concentrations of V even after a 6 week depletion phase.


Postnatal endocrine dysfunction resulting from prenatal exposure to carbofuran, diazinon or chlordane. Prenatal exposure to pesticides of three different classes initiated persistent postnatal endocrine dysfunction. Adrenal function and hepatic metabolism of corticosterone were studied in adult hybrid mice exposed during development to either an organophosphate (Diazinon), a carbamate (Carbofuran), or an organochlorine (Chlordane). Animals were exposed to relatively low levels of the toxins in utero and neonatally via the mothers' milk. Exposure to lower doses of the anticholinesterase compounds, Diazinon or Carbofuran, resulted in impairment of hepatic metabolism of corticosterone in vitro due to a loss in reductive capacity per unit liver weight. Plasma levels of corticosterone were also elevated in these animals, but without a concomitant increase in adrenal steroidogenesis in vitro. The effects of exposure to Chlordane were more complex. In male animals, exposure to lower doses of chlordane resulted in an increase in plasma corticosterone levels without an apparent increase in hepatic metabolism of corticosterone or adrenal steroidogenesis. In contrast, side-chain metabolism of corticosterone was decreased in female mice exposed to Chlordane. Similar effects on pituitary-adrenal function were not evident for the offspring of mice exposed to higher doses of the toxins. Possible mechanisms for this non-linear dose-response are discussed.


Quality assurance for pathology in rodent carcinogenesis tests. A large scale national carcinogenesis testing program requires quality assurance procedures for each scientific discipline, including pathology. The NCl Carcinogenesis Testing Program's pathology procedures involve the necropsy examination, histology, histopathologic diagnosis, data recording, and report writing. Each phase of the program requires specific quality assurance procedures, some of which are clerical, others scientific. In the latter case, a consensus from a group of pathologists serves to resolve differences of opinion. Only with the implementation of quality assurance procedures will the confidence in these tests be assured and quality maintained. Subsequently, modifications to established protocols may be discussed and accurately evaluated.


Dietary protein levels and aflatoxin B metabolism in rainbow trout (Salmo gairdneri). In an attempt to understand dietary protein effects upon aflatoxin B1-induced liver cancer in rainbow trout, the activities of several suspected aflatoxin B1 metabolizing enzyme systems were studied relative to protein intake. Fish fed diets containing 32 percent, 52  percent and 62 percent fish protein concentrate (FPC) were examined for hepatic cytochrome P-450 content and in vitro cytochrome c reductase, glutathione-S-epoxide transferase (GTr), epoxide hydrase (EH) and aldrin epoxidase (AE) activity. In addition, aflatoxin B1 conversion to aflatoxicol (AFL) was examined. A direct correlation was observed between increased FPC intake and cytochrome P-450 content and AFL production, with increases of 14 percent and 41 percent respectively. With increased FPC intake, decreases in EH (15 percent), GRr (20 percent), cytochrome c reductase (13 percent) and AE (50 percent) activities were noted. These findings are discussed in relation to AFB feeding trials reported earlier.


Hematologic changes in the rat during and after exposure to carbon monoxide. Rats were continuously exposed to 500 p.p.m. CO for 42 days. Hemoglobin concentration, hematocrit ratio, and erythrocyte count increased rapidly, with initial increases appearing after 4-7 days. Values of these parameters reached a plateau after 25-30 days of exposure 50 percent, 44 percent, and 42 percent above controls, respectively. Reticulocyte count peaked 600 percent above controls 7-10 days after initial exposure. This was reflected in the blood indices, mean corpuscular hemoglobin concentration (MCHC), mean corpuscular hemoglobin (MCH), and mean corpuscular volume (MCV). MCHC fell 6 percent by the fifth day of exposure, while MCH and MCV increased 11 percent and 16 percent respectively, by the seventh day. MCHC returned to control by the thirteenth day, while MCH and MCV remained elevated until the twenty-fifth day of CO exposure. During "stable" polycythemia both MCHC and MCH were depressed, while MCV was slightly elevated above the controls. Platelet count declined substantially within 20-25 days of exposure. Hb, Hct ratio and RBC count fell to control values in the time interval between 10 and 30 days post exposure. This was accompanied by transient fall in reticulocyte count from 2.5 percent (control value) to 0.1-0,2 percent between the twelfth and twenty-sixth day after exposure. Platelet count returned to the control value when polycythemia had subsided.


The dose-dependent fate of 1,4-dioxane in rats. A pharmacokinetic study was conducted to determine the fate of dioxane in rats at doses equivalent to those given in toxicological studies conducted previously. The results show that the fate of dioxane in rats is markedly dose-dependent due to a limited capacity to metabolize dioxane to beta-hydroxyethoxyacetic acid (HEAA). The pharmacokinetic data collected in support of these conclusions include plasma concentration-time curves for dioxane given to rats intravenously at dose levels from 3 to 1000 mg/kg and an inhalation study of 50 ppm dioxane vapors for 6 hr. The plasma curves at low doses by each route were linear, with half life values of about 1 hr. As the dose was increased above 10 mg/kg the plasma clearance rate decreased, the fraction of the dose excreted as HEAA decreased, and the fraction of the dose excreted as dioxane per se in the urine and expired in the breath increased. These data could be described by a one-compartment open system model with parallel first order (urinary and pulmonary excretion) and Michaelis-Menten (metabolism) type elimination kinetics. At saturation, the maximum velocity of the metabolism of dioxane ato HEAA was about 18 mg/kg/hr. Multiple daily oral doses of 1000 mg/kg, but not 10 mg/kg, were excreted more rapidly than equivalent single doses, indicating that at high daily doses dioxane induced its own metabolism. The correlation of the dose-dependent fate of dioxane with the results of toxicological studies in rats supports the conclusion that there is an apparent threshold for the toxic effects of dioxane which coincides with saturation of the metabolic pathway for its detoxification.


Parathion toxicity in perinatal rats born to spontaneously hypertensive dams. Placental transfer and fetal toxicity of pesticides have been documented in normotensive rats but no reports appear in the literature regarding the susceptibility of spontaneously hypertensive (SHR) perinates to pesticide challenge. This report describes the effects of prolonged parathion exposure to perinatal rats born to hypertensive dams. Ninety day old, spontaneously hypertensive (WKY strain) male and female rats were bred and vaginal plugs were used to determine that copulation had occurred. Parathion (0.01, 0.10 and 1.00 mg/kg) suspended in peanut oil was administered daily to the dam via oral intubation from day one of gestation to day fifteen of lactation, a total of thirty-seven days. On day twenty-four post partum the perinates were examined. Male and female SHR perinates exhibited a significant reduction in plasma cholinesterase at the 1.00 mg/kg dose level. Changes in relative organ weights, hematological parameters and serum enzymes were found. Heart rate was significantly reduced at the 0.01 mg/kg and 0.10 mg/kg dose levels. The results of this study indicate that exposure of SHR dams to parathion during gestation and lactation resulted in toxicological effects in the perinate basically similar to those seen in normotensive perinates.


Metabolite levels, redox states, and gluconeogenic enzyme activities in livers of rats fed diets containing 1,3-butanediol. Fat-free diets containing 1,3-butanediol (BD) were fed to rats. The concentration of metabolites in quick-frozen liver and the activities of kidney and liver gluconeogenic enzymes were examined. The free pyridine and adenine nucleotide ratios were calculated from measured intermediary metabolites. The concentrations of lactate, pyruvate, alpha-oxoglutarate, and glucose were significantly decreased in rats fed BD, while the acetoacetate and beta-hydroxybutyrate concentrations were increased in the BD-fed rats. The ratios of the free cytoplasmic [NAD+]/[NADH] and [NADP+]/[NADPH] were significantly decreased. Phosphoenolpyruvate carboxykinase activity was significantly increased in both kidney and liver of rats fed BD. These changes in metabolite levels and enzyme activities paralleled the effects seen in mild starvation, and were similar to reported changes observed when dietary fat was present.


Effects of pesticides on metabolism of steroid hormone by rodent liver microsomes. Liver microsomal steroid hydroxylating enzymes and prostatic testosterone-5alpha-reductase were studied in rat and mouse. Organochlorine and organophosphate pesticides tended to inhibit liver steroid hydroxylations, while carbofuran slightly stimulated them. Neither species was consistently more sensitive to pesticide effects than the other. All the pesticides bound to cytochrome P-450, producing Type I spectral changes. Values of Ks ranged from 1.9 to 8.7 mM for organochlorine and organophosphate compounds. Affinity for carbofuran was much lower (Ks=100-200mM).


Asbestos fibers in wines: relation to filtration process. Asbestos fibers have been counted, using the transmission electron microscope, in 42 wines from France and abroad. 15 samples were found to be significantly positive for chrysotile asbestos. Concentrations were in the range of 2 to 60 x 10(6) fibers/liter. Technical inquiries have shown that the asbestos content of the wines was related to the process by which they were filtered. On the other side, it has been tested that if one abolished the use of asbestos for filtering wines, they would not be altered from the oenological point of view.


Degradation of cadmium-thionein in rat liver and kidney. 3H-cystine and 115mCd were incorporated into hepatic and renal cadmium-thionein in response to a subcutaneous administration of 4.4 micronmol of Cd2+ containing 115mCd. Cadmium-thionein bound 115mCd reached a plateau by 24 hrs. and 72 hrs. after the Cd2+ injection in liver and kidney, respectively. The half-life (t 1/2) of 3-H-labeled hepatic cadmium-thionein was 3.5 days, whereas the average t 1/2 of the soluble proteins was 3.7 days. The t 1/2 of the soluble renal proteins was 3.8 days. In marked contrast, the 115mCd content of both hepatic and renal cadmium-thionein was virtually unchanged even 9 days after administration of this radionuclide. These data indicate that the protein moiety of metallothionein is degraded, although there appears to be a concomitant rebinding of Cd2+ to nascent thionein polypeptide chains. Thus the lack of metallothionein degradation, per se, does not account for the long-term retention of Cd2+ in liver and kidney during chronic exposure.


Monitoring and risk assessment by means of alkyl groups in hemoglobin in persons occupationally exposed to ethylene oxide. In persons occupationally exposed to ethylene oxide, i.e. under the conditions described by Dunkelberg and Hartmetz (1977), the degree of alkylation in histidine of hemoglobin was determined. Quantitative determination of N-3-(2-hydroxyethyl)histidine by mass fragmentography and by ion-exchange amino-acid analysis gave consistent results. Data are in agreement with the fast elimination from tissues (lambda = 4.6 hr-1, i.e. biological half-life about 9 min) found in the mouse. At the respiration rate of light work, and exposure dose of 1 ppm/hr results in a tissue dose that is estimated to involve a risk amounting to 1.101 mrad-equivalents of stochastic effects with a genetic mechanism.


Chronic mercuric chloride intoxication in the digestive system of Channa punctatus. The effect of a sublethal concentration (0.30 mg/l) of mercuric chloride exposure on the activities of alkaline phosphatase, acid phosphatase, amylase, trypsin, and pepsin has been examined at intervals of 7, 15, and 30 days in the digestive system of a teleost fish, Channa punctatus. An inhibition in the activity of all the above enzymes was noted after the first week of treatment. Treatment of the fishes for 15 days resulted in a marked increase in activity of all the enzymes. A slight fall in enzyme activity was recorded after 30 days, but the overall activity was higher than in control fishes.


The effects in rats and guinea pigs from six months exposures to sulfuric acid mist, ozone, and their combination. Rats and guinea pigs were exposed to 0.5 ppm ozone, 10 mg/m3 sulfuric acid mist, or their combination for 6 hrs/day, 5 days/week for six months. Exposure-related microscopic alterations were seen in the lungs of guinea pigs exposed to ozone alone or in combination with sulfuric acid mist. No other microscopic lesions were present in either rats or guinea pigs. No biologically meaningful synergistic effects were noted in animals exposed to the combination of ozone and sulfuric mist.


Alterations of rat intestinal disaccharide absorption by bile or conjugated bile acids. Taurocholate showed different effects on the jejunal sucrose absorption, depending on the concentration of the bile acid: 3 mmol/l taurocholate inhibited to a small extent (-7%), 10 mmol/l taurocholate had no effect and 30 mmol/l taurocholate increased the sucrose absorption by 17%. The sucrose hydrolysis was augmented by 20% in the presence of 30 mmol/l taurocholate. 2 mmol/l taurochenodeoxycholate caused an increase of sucrose hydrolysis(+ 37%) as well as of sucrose absorption (+ 12%) in the jejunum. Pooled rat bile induced a 21% inhibition of the sucrose hydrolysis, while the sucrose absorption was unchanged. The jejunal maltose hydrolysis was unaffected by 3 mmol/l taurocholate, whereas 10 or 30 mmol/l caused a minimal increase (+ 3%). The absorption of the resulting glucose was reduced to 84--92%. In the ileum 10 mmol/l taurocholate did not change the sucrose hydrolysis and absorption, whereas 2 mmol/l taurochenodeoxycholate induced a 30% decrease. The investigated bile acids had no effect on the microscopic structure of the small intestinal mucosa. Hypertonic solutions caused an accumulation and exfoliation of PAS-positive material at the top of the villi, independent of the presence or absence of bile acids.


Effect of ascorbic acid on oxygen consumption, glycolysis and lipid metabolism of diabetic rat testis. Ascorbic acid and diabetes, I. Alloxan diabetes caused a marked stimulation of endogenous oxygen uptake by rat testis tissues. However, the oxygen uptake in the presence of added glucose or pyruvate as substrate was significantly reduced. The ability of the testis tissues to utilize these substrates and to produce lactate was significantly inhibited in the diabetic animals. Alloxan diabetes also increased the levels of cholesterol, cholesterol esters, non-esterified fatty acids, triglycerides and phospholipids in rat testis tissues. Treatment of the diabetic rats with ascorbic acid caused more or less a normalization of all the parameters tested.


Evaluation of a degradation method for nitrosamine wastes. Nitrosamines are being used with increasing frequency in biomedical laboratories. Disposal of these potentially carcinogenic compounds requires a decontamination procedure that is simple, efficient, and economical. Degradation of nitrosamine wastes by alkaline reduction and the analytical techniques for evaluating this method have been explored. Efficiencies of degradation vary from 9.0 to greater than 99.9 percent of a group of ten nitrosamines.


Effect of subacute manganese feeding on serotonin metabolism in the rat. To clarify the effect of subacute manganese feeding on serotonin and mineral metabolism, Wistar rats were separated into two groups and fed two different diets, one a normal diet and the another a manganese-supplemented diet. After three weeks on these dietary regimens, the rats on the manganese-supplemented diet manifested the following abnormalities: blood pressure was decreased; brain serotonin was decreased; L-aromatic amino acid decarboxylase activity in brain was decreased. Manganese levels in heart, lung, and kidney increased, whereas sodium, potassium, magnesium and calcium levels in the brainstem decreased.


[Gas chromatographic determination of D-mannitol in body fluids (author's transl)]. A rapid, highly reproducible method is described for the determination of mannitol in body fluids. The method is based on the gas chromatography of the n-butylborate derivative. Recovery is greater than 90%, and the variation coefficient within the series is 1--3%.


Blood pressure and lead levels in children. Blood lead and hypertension are associated in adults. We attempted to duplicate this finding in a presumably more susceptible group of children. Small but statistically significant negative corelations were found between blood pressure and lead levels in these children. This indicated to us that the proposed positive relationship did not exist, and that the failure to detect such a relationship was not due to small sample size.


[Mass spectrometry and combined techniques in medicine, clinical chemistry and clinical biochemistry. Report on the conference at the Medizinische Klinik of the University of Tübingen on November 14--15, 1977 (author's transl)]. Mass spectrometry, especially in combination with gas chromatography, is the most flexible and powerful analytical technique available today for organic substances, with the exception of macromolecules. It is distinguished by vary high sensitivity combined with high specificity, and enables the identification and quantification of substances in biological material even in very low concentration. The conference was divided into five sessions: Main areas of application, Hormones and active substances, Profile analyses, Methodical and theoretical aspects, Pharmacological and toxicological applications. It was the goal of the symposium to gather scientists and clinicians and to define the scope and place of mass spectrometry in clinical chemical and medical research, and in routine analysis, and to identify the kind of problems it can help to solve.


A controlled field trial of physiological responses to organophosphate residues in farm workers. Blood acetylcholinesterase (ACHE) and pseudocholinesterase (PCHE) activity and urinary dialkyl phosphate (DAP) excretion were measured in a group of 15 male agriculture field workers during a five-day thinning operation in a Northern California peach orchard. Eight men were randomly assigned to work in a Guthion-treated plot, and seven men to work in an adjoining plot free from organophosphate residues. Foliage samples were taken to measure dislodgeable and total Guthion residues. The daily mean percent change in the ACHE and in the PCHE activity was less than -10.0 percent of baseline values for each group of men. Mean ACHE activity of workers in the Guthion treated plot was different from that of workers in the control plot on the fifth exposure day. The mean PCHE activity of workers in the Guthion treated plot was not different from that of workers in the control plot. Daily group-mean urinary metabolite excretion levels for workers exposed to Guthion residues were highly correlated with their daily group-mean percent change in ACHE activity. No urinary metabolites were detected in workers in the control plot. Decay in Guthion residues was markedly slower in this trial than in a comparable study conducted one year previously, emphasizing the difficulty in setting re-entry intervals based on time elapsed from pesticide application. Suggestions were made to extend the time interval of future studies on the human health effects of organophosphate residue exposure, and to further refine urinary metabolite surveillance methods toward the goal of establishing a threshold level of metabolites which would correspond to meaningful exposure to these pesticides residues.


A computer-based toxicology search system. An interactive computer search system, based on the National Institute for Occupational Safety and Health's Registry of Toxic Effects of Chemicals (NIOSH-RTECS) has been developed. This system permits the location and retrieval of specified toxicity data defined by test animal, dosage method, toxicity level, and compound identity. All available toxicity data for a given chemical substance, identified by name or structure, may be retrieved using either the Chemical Abstracts Service (CAS) Registry Number or the RTECS Accession Number for that compound. The search system is running upon an international computer network, and may be used by anyone interested on a fee-for-service basis.


Behavioural and neurochemical consequences of neonatal exposure to lead in rats. Locomotor activity, lead content and concentrations of norepinephrine (NE), dopamine (DA), 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) in discrete brain regions were examined in rats given a fixed oral dose (50 microgram/pup) of inorganic lead from birth till weaning and then kept on water containing 80 ppm lead until either 8 or 12 weeks of age. Lead-exposed animals showed an increase (by 74 and 93 percent, respectively) in locomotor activity at 6 and 8 weeks of age. By 12 weeks, the motor activity returned to control values both in animals which were withdrawn from lead treatment at 8 weeks of age and in those continued on lead. Lead levels in brain at 8 weeks of age were highest in hypothalamus and striatum. Significant decreases in cortical NE, DA and 5-HT, mildbrain DA, striatal NE and hypothalamic DA and 5-HT were found in brains of 8 week-old hyperactive rats; in contrast, NE levels in the midbrain were elevated. Whereas the decreases in 5-HT remained unchanged, alterations in regional concentration of catecholamines were no longer evident in lead-exposed animals whose motor activity returned to normal by 12 weeks of age or in rats withdrawn from lead at age of 8 weeks. Alterations in regional levels of NE and DA appear to be associated with lead-induced increase in locomotor activity, while changes in 5-HT metabolism may result from a non-specific toxic effect of the metal.


Trends and aspects in clinical chemistry. This paper first seeks to evaluate current trends in methodology and technology and discusses possible implications for the future of clinical chemistry, whose range and diversity of tasks are carefully defined. It is thought that the remarkable development in the field of immunological methods, in the general sense of the work, will continue for the years to come. One other principle, which it is predicted will play an increasing role, is thermometry for the determination of enthalpy. Similarly, new developments in the fields of bio- and chemoluminescence offer interesting possibilities. The impact of the computer in clinical chemistry is also discused. Secondly, the double role of clinical chemistry as a diagnostic speciality and as an academic field is analyzed. On the one hand, the need for closer cooperation both with other diagnostic subspecialities and with other medical clinical disciplines is stressed. In particular, newly organized Departments of Laboratory Medicine encompassing microbiology, cytology, nuclear medicine, toxicology etc. might contribute greatly to interdisciplinary understanding. On the other hand, problems of clinical medicine and of certain areas within biological research should be at the center of interest of the future research-oriented clinical chemist.


Cerium tissue/organ distribution and alterations in open field and exploratory behavior following acute exposure of the mouse to cerium (citrate). Cerium chloride (1:3 complex with sodium citrate) was administered to male Swiss mice (6 to 8 weeks old) either intragastrically or subcutaneously at the 7 day LD5 or LD25 level. Open field behavior (ambulations, rearings) was quantified and tissue/organ Ce levels determined at 4 hr., 1, 3 or 7 days post administration. Via the i.g. route, Ce was poorly absorbed resulting in no observable behavioral alterations and no correlations between behavior and tissue levels. Via the s.c. route, Ce significantly (p less than 0.05) depressed ambulations and rearings, mainly at short times following administration of the LD25 dose. Analogous findings were obtained in a separate study of exploratory behavior. There was a significant (p less than 0.05) correlation between open field behavior and tissue Ce levels: thus, rearings were inversely correlated with lung, stomach, cerebrum, cerebellum and brain stem Ce levels and ambulations were inversely correlated with liver, kidney, lung, blood, stomach, intestine, muscle, cerebrum, cerebellum and brain stem levels. Spleen Ce levels and ambulations were directly correlated and it is speculated that the spleen may serve a protective function in the case of Ce intoxication.


N-(4-azido-2-nitrophenyl)-2-aminoethylsulfonate (NAP-taurine) as a photoaffinity probe for identifying membrane components containing the modifier site of the human red blood cell anion exchange system. Exposure of cells to intense light with the photoactivatable reagent, N-(4-azido-2-nitrophenyl)-2-aminoethylsulfonate (NAP-taurine), present in the external medium results in irreversible inhibition of chloride or sulfate exchange. This irreversible inhibition seems to result from covalent reaction with the same sites to which NAP-taurine binds reversibly in the dark. As shown in the preceding paper, high chloride concentrations decrease the reversible inhibition by NAP-taurine in the dark, in a manner suggesting that NAP-taurine and chloride compete for the modifier site of the anion transport system. In a similar fashion, high chloride concentrations in the medium during exposure to light cause a decrease in both the irreversible binding of NAP-taurine to the membrane and the inhibition of chloride exchange. Most of the chloride-sensitive irreversibly bound NAP-taurine is found in the 95,000 dalton polypeptide known as band 3 and, after pronase treatment of intact cells, in the 65,000 dalton fragment of this protein produced by proteolytic cleavage. After chymotrypsin treatment of ghosts, the NAP-taurine is localized in the 17,000 dalton transmembrane portion of this fragment. Although the possible involvement of minor labeled proteins cannot be rigorously excluded, the modifier site labeled by external NAP-taurine appears, therefore, to be located in the same portion of the 95,000 dalton polypeptide as is the transport site.


Asymmetry of the red cell anion exchange system. Different mechanisms of reversible inhibition by N-(4-azido-2-nitrophenyl)-2-aminoethylsulfonate (NAP-taurine) at the inside and outside of the membrane. In the dark, the photoaffinity reagent, N-(4-azido-2-nitrophenyl)-2-aminoethylsulfonate (NAP-taurine), acts as a reversible inhibitor of red cell anion exchange when it is present either within the cell or in the external solution. A detailed analysis of the inhibition kinetics, however, reveals substantial differences in the responses to the probe at the two sides of the membrane. On the inside of the cell, NAP-taurine is a relatively low affinity inhibitor of chloride exchange (Ki = 370 microM). Both the effects of chloride on NAP-taurine inhibition and the affinity of NAP-taurine for the system as a substrate are consistent with the concept that internal NAP-taurine competes with chloride for the substrate site of the anion exchange system. External NAP-taurine, on the other hand, is a far more potent inhibitor of chloride exchange (Ki = 20 microM). It acts at a site of considerably lower affinity for chloride than the substrate site, probably the modifier site, at which halide anions are reported to cause a noncompetitive inhibition of chloride transport. NAP-taurine therefore seems to interact preferentially with either the substrate or modifier site of the transport system, depending on the side of the membrane at which it is present. It is suggested that the modifier site is accessible to NAP-taurine only from the outside whereas the transport site may be accessible from either side.


Filament interaction monitored by light scattering in skinned fibers. The intensity of light scattered by chemically skinned rabbit psoas fibers in relaxed, rigor, and activated states was monitored at 90 degrees to the incident beam. In the relaxed state, scattering varied in proportion to the volume of muscle in the beam. Scattering increased to 2.3 times the resting value when rigor was induced by withdrawal of MgATP or when the myofibrils were activated by the caffeine-induced release of Ca from the sarcoplasmic reticulum. The rigor-induced increase in scattering decreased monotonically when MgATP was reintroduced stepwise (0-100 microM). This decrease in scattering was accompanied by an increase in tension up to an optimum MgATP level of approximately 10 microM, and then tension decreased at higher concentrations (10-100 microM). The increase in scattering during both rigor and activation was dependent upon fiber length. At lengths when thick-thin filament overlap was near zero, the light signal due to rigor and activation fell to within 10% of the signal for the relaxed fiber at that length. The signal during rigor increased only minimally (approximately 10%) when stretch (approximately 1%) was applied. This increase in signal was small despite a measured 5- to 10-fold increase in tension and an estimated twofold increase in stiffness. Thus, the increased light scattering caused by rigor and activation depends on filament overlap and not tension, stiffness, or substrate binding.


Myofilament-generated tension oscillations during partial calcium activation and activation dependence of the sarcomere length-tension relation of skinned cardiac cells. During partial Ca2+ activation, skinned cardiac cells with sarcoplasmic reticulum destroyed by detergent developed spontaneous tension oscillations consisting of cycles (0.1-1 Hz) of rapid decrease of tension corresponding to the yield of some sarcomeres and slow redevelopment of tension corresponding to the reshortening of these sarcomeres. Such myofilament-generated tension oscillations were never observed during the full activation induced by a saturating [free Ca2+] or during the rigor tension induced by decreasing [MgATP] in the absence of free Ca2+ or when the mean sarcomere length (SL) of the preparation was greater than 3.10 microm during partial Ca2+ activation. A stiff parallel elastic element borne by a structure that could be digested by elastase hindered the study of the SL--active tension diagram in 8-13-microm-wide skinned cells from the rat ventricle, but this study was possible in 2-7-microm-wide myofibril bundles from the frog or dog ventricle. During rigor the tension decreased linearly when SL was increased from 2.35 to 3.80 microm. During full Ca2+ activation the tension decreased by less than 20% when SL was increased from 2.35 to approximately 3.10 microm. During partial Ca2+ activation the tension increased when SL was increased from 2.35 to 3.00 microm. From this observation of an apparent increase in the sensitivity of the myofilaments to Ca2+ induced by increasing SL during partial Ca2+ activation, a model was proposed that describes the tension oscillations and permits the derivation of the maximal velocity of shortening (Vmax). Vmax was increased by increasing [free Ca2+] or decreasing [free Mg2+] but not by increasing SL.


[Chromosome 5q-- in the medullar cells of a patient with anaemia which later developed into acute non-differentiated leukaemia (author's transl)]. The authors report the observation of a 76-year-old man who since 1974 had a persistent anaemia considered as a pre-leukaemic state. The patient was hospitalized in May 1977 with fever and severe asthenia. The laboratory results indicated a probable diagnosis of acute non-differentiated leukaemia of stem cells. In spite of treatment, the anaemia grew worse, the leukocytosis accompanied by blast cells became more pronounced, a massive thrombopenia occurred and the patient died in irreversible shock. Cytogenetic examination done on a medullar culture revealed the presence in all the cells of a chromosome No. 5 with the long arms deleted : 46,XY,5q--. This rare medullar anomaly was reported for the first time in 1974-1975 by the Louvain school (Van den Berghe, Sokal, et al.) in a group of refractory anaemias. It has also been described in association with other chromosomal aberrations, in anaemias or other hemopathies which all developed into acute myeloblastic leukaemia. The clinical evolution and the cytogenetic data of the patient presented here are compared with those of other cases of 5q-- published in the literature, and the significance of this 5q-- chromosome aberration in hemopathies is discussed.


Inherited parital duplication deficiency of chromosome 15 (p12;q22). Description of a boy aged 20 months presenting growth and mental retardation as well as several minor anomalies : brachycephaly, antimongoloid slant of the palpebral fissures, dystopia canthorum, broad nose, low set ears and short fingers. Chromosome analysis revealed an abnormal No. 15 with duplication of the distal half segment of its long arm (q22 leads to qter) and deficiency of the distal band of its short arm (p13). This anomaly was inherited by recombination aneusomy of a pericentric inversion carried by his mother : inv(15) (p12;q22).


[Screening for heterozygotes in a large family suffering from Steinert's disease with varying clinical manifestations (author's transl)]. Starting with 4 probands, our study for the early detection of heterozygotes enabled us to investigate a family suffering from myotonic dystrophy, through 8 generations. Out of 274 family members, 209 are still living, 101 of whom were examined by us personally. We discovered, in all, 12 patients with Steinert's disease (one of which was a childhood case), 14 with a "forme fruste" (two of which were infantile cases) and 2 patients with only a myotonic cataract. The clinical picture varied a great deal amongst the patients, but showed in general a rather benign evolution. With respect to diagnostic methods, most of the 24 secondary cases were detected through clinical examination preceded by a good case history (6 out of the 8 classical forms, and all the 14 "formes frustes"). Slit lamp examination was indispensable for the recognition of the first changes in the lenses of two young adults and, likewise, for the detection of two isolated myotonic cataracts. The electromyography showed characteristic anomalies in 3 patients; in addition, non-specific alterations existed in 3 other patients who showed only slight signs of the disease. Neither the gammaglobulins nor the ABH secretion factors were of any diagnostic aid in this family. Our investigation is relevant in the context of the prevention of hereditary conditions, in particular Steinert's disease. Indeed, owing to the early recognition of the heterozygotes, an adequate genetic prognosis can be given in due time to the family members at risk.


[Non-fluorescent Y chromosome in a 45,X/46,XY mosaic (author's transl)]. The case of a 18-year-old boy with small testes and deficient growth is reported. Histological examinations revealed an abnormal structure of the testicular tissue. The X chromatin test in buccal smears and the Y chromatin test in peripheral blood lymphocytes were negative. By chromosomal studies a 45,X/46,XY mosaicism was diagnosed. The Y chromosome did not show the typical fluorescence. Autoradiographic as well as Q- and G-banding techniques were performed in both the patient and his father. The patient's Y chromosome was shorter than his father's one, but longer than the non-fluorescent part of the paternal Y. The autoradiographic grain counts, Q- and G-band patterns showed a difference between the proband's Y chromosome and that of the father. The mechanism of the observed aberration is discussed.


Supernumerary small chromosomal anomaly: report of three cases including one with a familial inversion of chromosome 5. Three cases of a small supernumerary chromosomal anomaly of essentially unknown origin associated with wide variability of clinical expression are reported. Case II has, in addition, a pericentric inversion of chromosome 5, which enables us to propose a mechanism, involving an unsuccessful crossing over, for the origin of the supernumerary chromosome.


Two mechanisms for spreading depression in the chicken retina. Two mechanisms have been proposed to explain spreading depression (SD): one based on a release of glutamate (Van Harreveld, 1959), and the other on a release of potassium (Grafstein 1956) from neuronal elements. Both glutamate and KCl cause transparency changes in the retina, comparable to those occurring in this tissue during SD. The glutamate effect is inhibited by MgCl2 (10mM), in contrast to the transparency change due to KCl which is not affected by Mg++. Also SD is usually inhibited by MgCl2 which suggests that such SDs are based on a glutamate release. Impairment of the tissue metabolism promotes SDs which are insensitive to MgCl2. The resulting failure of the mechanisms that transport K+ and glutamate which leak out of the intracellular compartment back into the cells and fibers, seems to be involved in the generation of Mg++ insensitive SDs. This may facilitate either K-based SDs or glutamate-based SDs since the inhibitory effect of Mg++ is counteracted by an enhanced glutamate concentration. Both proposed mechanisms for SD seem to be possible under special circumstances.


Lack of limb motor asymmetry in the neonate. Neonates were examined for evidence of lateralization of motor function. The stepping test was done and the foot that moved first was recorded. The reaction of both arms to avoid an obstacle was also tested. No evidence for lateralization was found. Previous studies in the neonate have shown asymmetry of anatomical structures subserving language, and functional asymmetry of auditory functions and head position. However, the development of limb handedness occurs only at a later age.


The brain-specific S-100 protein on neuronal cell membranes. The S-100 protein has been localized to the neuronal plasma membranes of isolated Deiters' neurons by fluorescence microscopy using fluorescein-conjugated antiserum to the protein and by immunoelectron microscopy using peroxidase-conjugated anti-S-100 antiserum. In the present study this is shown also by incubating neurons with Sepharose 4B or methylacrylate spherules to which were coupled anti-S-100 antibodies. The specificity of the antiserum is discussed in the text. The technique described can be used to study the topography of antigenic characteristics of nerve cells by using antisera insolubilized on spherules of suitable size.


An electron-microscopic study of avirulent and virulent Semliki forest virus in the brains of different ages of mice. Ultrastructural studies of brains infected with avirulent and virulent strains of Semliki forest virus (SFV) were performed in 2-7, 14, 19, and 21-28 day old mice. Mature virus particles, dense clumps of fine granules, spherules and advanced stages of viral development i.e. cytopathic vacuoles, Type II (CPV II) are seen in the brains at all ages with the virulent strain which is pathogenic to all age group of mice. In the avirulent strain infection which is pathogenic to mice below 15 days old, no mature virus particles or advanced stages of viral development are seen in 19 day old and adult mice in spite of high virus titres. However, dense clumps of fine granules and spherules are seen which seem to have the capacity to develop into lethal highly infectious mature virus when reinoculated into 2-7 day old mice. It is suggested that the dense clumps of fine granules and spherules are very early viral forms, which are seen in all age groups of mice. The cut-off mechanism in pathogenicity of the avirulent strain occurs in mice around 14 days old. Though some mature virus particles and advanced viral developmental stages are seen in these mice they were much less frequent compared to baby mice. Lymphoblastic type cells are numerous in this age group. These cells are seen more frequently in all ages of mice infected with the avirulent strain as compared to the virulent strain. These mononuclear cells can have an immunological role and may play a part in limiting the process of viral maturation and hence preventing death. Polymorphs and macrophages are rare with the avirulent infection but are the predominant infiltrating cells in the virulent strain infections. With the avirulent infections the astrocytes show hypertrophy and intranuclear inclusions are seen in them.


Ischaemic brain damage in fatal non-missile head injuries. The incidence and distribution of ischaemic brain damage in a consecutive series of 151 patients who died as a result of a non-missile head injury in the Institute of Neurological Sciences was determined on the basis of a comprehensive neuropathological and neurohistological examination. Ischaemic damage was identified in 138 cases (91%) even after excluding cases who only had necrosis and infarction related to contusions or fat embolism, and infarction in the brain stem of the type conventionally associated with raised intracranial pressure. The ischaemic damage was assessed as severe in 37 (27%), moderately severe in 59 (43%) and mild in 42 (30%), and in the 138 cases with ischaemic brain damage it was found more frequently in the hippocampus (122 cases; 81%), and in the basal ganglia (119 cases; 79%) than in the cerebral cortex (70 cases; 46%) and in the cerebellum (67 cases; 44%). There were statistically significant correlations between ischaemic brain damage and either an episode of hypoxia or of raised intracranial pressure. From the nature of the brain damage it seems likely that much of it was due to a reduction in the cerebral perfusion pressure. This study has shown that ischaemic brain damage is common after head injury, that at least a proportion of it is probably avoidable, and that it is more important as a cause of mortality and morbidity after head injury than has been hitherto realised.


Metabolic implications of distal atrophy. Carbohydrate metabolism in centronuclear myopathy. Centronuclear myopathy, like myotonic dystrophy, is characterized by muscle wasting and type 1 fiber atrophy. To determine whether this disorder might include a derangement in carbohydrate metabolism similar to that in myotonic dystrophy, 3 comparably wasted patients with centronuclear myopathy, myotonic dystrophy, and neurogenic atrophy were investigated. The patient with centronuclear myopathy had mild glucose intolerance and hypoinsulinemia after oral glucose ingestion in bold contrast to the normal glucose tolerance and hyperinsulinemia observed in the myotonic dystrophy patient. No abnormality was seen in oral glucose tolerance in the patient with neurogenic atrophy, and all 3 patients had normal insulin tolerance. Forearm insulin infusion demonstrated normal stimulation of muscle glucose uptake in the patients with centronuclear myopathy and neurogenic atrophy in contrast to the markedly diminished response to insulin seen in the patient with myotonic dystrophy. These data indicate that neither distal wasting or type 1 fiber atrophy are responsible for the abnormalities in carbohydrate metabolism in myotonic dystrophy.


Are x-rays the ultimate? Proton (heavy ion) radiography in neurologic diagnosis. Radiations other than those of the electromagnetic spectrum or of sound may be used for neurologic diagnosis. These consist of beams of sub-atomic particles, particularly of protons and other heavy ions. With these beams radiographs of unusually high contrast are obtained for the visualization and differentiation of the soft body tissues at very low doses (down to approximately two orders of magnitude less than with x-rays). The method is practical for use in hospitals and has potential for screening purposes. The properties of these and other sub-atomic particles are reviewed for their diagnostic and basic research potential.


Ultrastructural evidence of "abortive" regeneration in murine muscular dystrophy. Triceps and gastrocnemius muscles from dystrophic (129 ReJ dy/dy) and normal mice were examined by electron microscopy at different stages in development (birth to 6 months). A qualitative assessment was made of the incidence and success of regeneration. Mitotic figures were seen in satellite cells in two-week-old dystrophic muscle. Well-differentiated myotubes were seen in dystrophic muscles at all ages but the incidence of regeneration was greatly reduced in the older dystrophic muscles. Myotubes in areas of regeneration up to two months of age frequently showed atypical or degenerative features. It is concluded that regeneration of dystrophic mouse muscle proceeds normally to the myotube stage after which differentiation becomes aberrant and degeneration may occur. This "abortive" regeneration probably contributes to the progression of the myopathy.


Abnormal neuronal migration, deranged cerebral cortical organization, and diffuse white matter astrocytosis of human fetal brain: a major effect of methylmercury poisoning in utero. Detailed clinical and neuropathological studies have been made in two fullterm newborn human infants who were exposed to methylmercury in utero as a result of maternal ingestion of methylmercury-contaminated bread in early phases of pregnancy. High levels of mercury were detected in various regions of the brain at autopsy. Study of the brains revealed a disturbance in the development in both cases, consisting essentially of an incomplete or abnormal migration of neurons to the cerebellar and cerebral cortices, and deranged cortical organization of the cerebrum. There were numerous heterotopic neurons, both isolated and in groups, in the white matter of cerebrum and cerebellum and the laminar cortical pattern of the laminar cortical pattern of the cerebrum was disturbed in many regions as was shown by the irregular groupings and the deranged alignment of cortical. Prominent in the white matter of the cerebrum and the cerebellum was diffuse gemistocytic astrocytosis accompanied by an accumulation of mercury grains in their cytoplasm. These findings indicate a high degree of vulnerability of human fetal brain to maternal intoxication by methylmercury. A major effect appears to be related to faulty development and not to destructive focal neuronal damage as has been observed in mercury intoxicaiton in adults and children exposed postnatally.


Splanchnic preganglionic neurons in man. III. Morphometry of myelinated fibers of rami communicantes. The myelinated fiber (MF) composition of T6-T8 Rami Communicantes were obtained in 9 healthy persons of various ages. The textbook picture that distal rami (DR) contain all of the myelinated fibers and therefore are white, while proximal rami (PR) contain none of them and therefore are grey must be modified. We found that DR usually contained abundant MFs and that PR concordance was found between segmental numbers of intermediolateral nuclei cytons, ventral root small myelinated fibers (SMFs), and rami total small MFs to suggest that both rami probably contain the distal myelinated axons of preganglionic autonomic fibers. Finally, there was an attrition of total MFs of rami with age, similar to what we had previously found for ILC cytons and for root SMFs. The decrease in number of pre-ganglionic autonomic neurons with age is thought to be of sufficient magnitude to account for the dysautonomia of the elderly.


The number and sizes of reconstructed peripheral autonomic, sensory and motor neurons in a case or dysautonomia. Motor, spinal ganglion, intermediolateral and sympathetic trunk neurons were reconstructed by morphometric sampling of their cell bodies at L5 and T7 segments and at various levels of spinal roots and peripheral nerves in a 31-year-old patient with dysautonomia and compared to reference cases. The patient had strikingly fewer intermediate motoneuron column neurons and intermediate ventral root axons (probably gamma motoneurons), spinal ganglion neurons, preganglionic autonomic neurons and sympathetic trunk neurons that did controls (approximately 10--30% of reference values). The striking agreement between selective absence of intermediate-diameter cytons (Ci) and of intermediate diameter myelinated fibers (Ai), which are thought to be gamma efferent, of L5 motoneuron columns provides further confirmation to our previous suggestion that the Ci peak of motoneuron columns are somas of gamma efferent neurons. The number and size of alpha motoneuron cell bodies and their proximal axons were like those of controls but their distal axons were probably atrophic. This finding probably explains the small reduction in maximum conduction velocity of motor nerve fibers found in this disorder. The brunt of the pathologic process in this disorder has been borne by intermediate and small neurons preferentially.


Effects of neurotoxic industrial solvents on cultured neuroblastoma cells: methyl n-butyl ketone, n-hexane and derivatives. The neurotoxic effects of the commercial organic solvents n-hexane and methyl n-butyl ketone (MBK), recently discovered to cause profound peripheral neuropathy in man, were studied in neuronal-like cells in tissue culture. These agents are known to induce marked proliferation of 10nm neurofilaments in peripheral and central axons of both humans and rats. In a murine neuroblastoma cell line, previously reported to show filamentous hyperplasia when exposed to aluminum ions, both MBK and n-hexane induced a highly reproducible series of cytotoxic effects at the light and electron microscopic levels and caused dose-dependent inhibition of cellular proliferation. In contrast, two closely related but clinically non-toxic solvents, methyl isobutyl ketone and methyl ethyl ketone, caused little or no cytopathological or growth inhibiting effects. MBK and its major water soluble derivative, 2,5-hexane dione (HD), produced identical cytotoxic changes in vitro, supporting the postulate that HD is the toxically active agent in victims exposed to MBK. Although MBKlthought MBK and n-hexand adversely affected the extension of maintenance of neuritic processes, electron microscopy and immunofluorescent reaction failed to reveal any proliferation of 10 nm cytoplasmic filaments in the intoxicated cells. Also, these agents had no deleterious effect on in vitro brain microtubule polymerization. In contrast, aluminum ions produced a doserelated inhibition of neurotubule assembly, similar to that seen with the filament-inducing agents colchicine and vinblastine. The results suggest that the fibrous cytoskeleton may not be the primary or essential target of MBK n-hexane and related human neurotoxins.


Polyneuropathies and CNS protein metabolism. III. Changes in protein synthesis rate induced by acrylamide intoxication. A defect in neuronal protein metabolism has been proposed as one of the primary, molecular events underlying the development of polyneuropathies of the dying back type. Using acrylamide-intoxication as an experimental model to study these polyneuropathies, changes in leucine-incorporation into proteins disability. Proteinsynthesis rates were determined in vivo using flooding concentrations of [1-14C]valine as the precusor. Under conditions of acute and of chronic intoxication, a decrease in synthesis rate was measured preceding the loss of functional ability. Similar changes in protein synthesis rate were observed in peripheral tissues such as heart muscle and liver showing the general toxicity of acrylamide. Methylene bisacrylamide, that was used to discriminate between the neurotoxic action of acrylamide and its systemic effects, interfered with protein synthesis rates in a comparable way. No change in protein synthesis rate was observed under in vitro conditions suggesting that the interference of acrylamide with the synthetic machinery for protein synthesis in vivo is mediated by one or more as yet unknown indirect factors.


Brain ultrastructure in Reye's disease. II. Acute injury and recovery processes in three children. Acute and recovery biopsies of three patients with Reye's Disease are described. Pleomorphic changes of neuronal mitochondria were identified in all of the acute biopsies, similar in appearance to the characteristic alterations of hepatic mitochondria. Distinctive myelin bleb formation may be directly attributable to the mitochondrial injury. The mitochondrial lesion is reversible. There is morphologic evidence for regeneration and repair of myelin; but the presence of myelin ovoids at long intervals after recovery indicates a loss of some myelinated fibers. The neuronal mitochondrial changes, pleomorphism with matrix expansion, and myelin bleb formation, reflect a specific biochemical injury be attributable to ischemic injury secondary to brain edema.


Starch granulomata of the endocardium.

Starch granulomata of the endocardium. Two cases of granuloma of the endocardium following cardic catherterisation are described. In each case the granuloma consisted essentially of macrophages associated with intracellular and extracellular starch granules, derived presumably from the glove powder used at operation. No previous cases of this condition have been found in the literature.


Myoepithelial differentiation and basal lamina deposition in fibroadenoma and adenosis of the breast. Sixteen cases of breast fibroadenomas and 11 of adenosis were studied ultrastructurally; emphasis was placed on the patterns of myoepithelial differentiation and the number and appearance of the basal laminae. Ducts of both fibroadenomas and adenosis showed well differentiated, peripherally arranged myoepithelial elements with conspicuous cytoplasmic filaments and numerous hemidesmosomes; focal myoepithelial multilayering occurred. Myoepithelial cells exhibited complex, convoluted cytoplasmic processes extending into the stroma and resulting in the formation of pseudocysts containing stromal material. Basal lamina deposition was invariably found; basal lamina reduplication was extremely frequent. Basal lamina discontinuities with cytoplasmic processes extending directly into the stroma were seen in adenosis. Myoepithelial features and conspicuous basal lamina deposition indicate advanced differentiation and correlate well with the benign prognosis of these lesions. The focal basal lamina gaps in adenosis may be significant in the long-term evolution of this and similar dysplastic processes.


Splenic lipofuscinosis in mice.

Splenic lipofuscinosis in mice. Autopsy examination of young adult mice revealed a characteristic pigmentation of the anterior splenic pole occurring in a high proportion (8-34 per cent) of three mouse strains and two sublines. Histological studies identified the pigment as lipofuscin and electron microscopy provided supporting evidence. Preliminary results are consistent with the hypothesis that lipofuscin may represent non metabolisable debris from cellular breakdown associated with lysosomal activity.


Angiogenic activity in culture supernatant of antigen-stimulated lymph node cells. The culture supernatant of antigen- and phytohaemagglutinin-stimulated lymph node cells contained angiogenic activity when applied to hamster cheek pouch vascular membranes. New capillary growth was observed about 7 days after such application. This activity was generated by culturing lymph node cells with antigens for at least 12 hr, while migration inhibitory factor (MIF) was detected in the culture supernatant of 6 hr cultures. The angiogenic activity was separated from blastogenic activity, clot-promoting activity and antibody activity. However, it was not completely separated from MIF by gel-filtration. The molecular weight of the angiogenic activity was estimated to be between 35,000 and 55,000 daltons.


Eosinophilic infiltrates in carcinoma of the urinary bladder unassociated with schistosomiasis. Two hundred and twenty-four biopsies from 151 patients with urinary bladder neoplasms have been studied in order to investigate the incidence of and possible causes for the infiltration of eosinophils. Cases of schistosomiasis were excluded from this study. Of these biopsies, 16 showed a heavy infiltrate 26 a moderate, 61 minimal and 121 no eosinophilic infiltrate. No correlation could be found between the degree of infiltrate and age, sex or tumour type. There was some statistically significant correlation between the eosinophilic infiltrate and stromal invasion and/or tumour necrosis. There was a strong statistical correlation between this infiltrate and previous trauma (biopsy) which was supported by the study of bladder biopsies from patients without neoplasms.


A teratoma of the lung containing thymic tissue. A case of a benign, cystic intrapulmonary teratoma occurring in the left lobe of a 63-yr-old female is described and the typical clinical symptoms and distinguishing X-ray appearances which may be helpful in diagnosing this rare tumour are mentioned. The connection between the tumor and the segmental bronchus clearly established the true intrapulmonary nature of the lesion in this case and the unusual finding of thymic tissue within the wall supports previous speculation regarding the possible thymic origin of these neoplasms.


The growth of embryonic brain tissue transplanted subcutaneously in rats. An acute inflammatory exudate possesses mitogenic activity in that it is able to induce both DNA synthesis and proliferation of macrophages in vitro. This activity is reduced however if the inflammatory exudate is obtained from irradiated rats (900 r). Transfer of bone marrow syngeneic cells into irradiated rats does not reverse this reduction. On the contrary the decrease of mitogenic activity is more pronounced. On the other hand transfer of thymic syngeneic cells not only restores the mitogenic activity of inflammatory exudate from irradiated rats but increases it. Transfer of both types of cell together fully restores the mitogenic activity of inflammatory exudate. It is postulated that the mitogenic activity of inflammatory exudate could be related to thymic cells and that T lymphocytes may be involved in non-specific inflammatory reactions.


Development of Tetrapetalonema marmosetae to the infective stage in Culicoides hollensis and C. furens. Development of the microfilaria of Tetrapetalonema marmosetae to the infective stage is described in 2 species of biting midges, Culicoides furens and C. hollensis. Development takes place in the thoracic muscles where the microfilaria requires 8 days to reach the third, or infective, stage. These observations suggest that species of Culicoides are the probable natural vectors of T. marmosetae in enzootic areas and that possibly a wide range of midges will serve as suitable vectors for the parasite in the laboratory. The elucidation of the life cycle, the first for a filaria from a neotropical primate, opens the way for the maintenance of this parasite in the laboratory and provides another useful tool for experimental study.


The spin method for recovering tissue larvae and its use in evaluating C57BL/6 mice as a model for the study of resistance to infection with Ascaris suum. A centrifugation method for recovering tissue larvae is described and is proven to be superior to both Baerman and tissue digest methods for recovering larvae of Ascaris suum from the liver and lungs of infected C57BL/6 mice. Using the spin method for harvesting larvae, C57BL/6 mice were evaluated for their suitability in studies on specific host immunity to infection with A. suum.


Patent Toxocara canis infection in ascarid-naive dogs. The effect of feeding different numbers of Toxocara canis eggs on patent intestinal infections was studied in 45 ascarid-naive 62--64-day-old pups and 6 adult dogs. Twenty-four of 25 pups fed 10 to 1,000 eggs developed patent intestinal infections, whereas none of the 20 pups fed 10,000 eggs developed patent intestinal infection. Three of 6 presumably ascarid-naive dogs, 7, 10, and 52 months old fed 100 eggs each, developed intestinal infections.


Trichostrongylus colubriformis: cultivation of free-living stages. Successful cultivation of Trichostrongylus colubriformis from hatched first-stage to third-stage larvae was achieved in media containing NCTC 135, chick embryo extract, fetal calf serum, and either lactalbumin hydrolysate or freshly prepared baker's yeast extract. Medium Tc5, containing yeast extract, was the simplest medium with optimal results. Cultured third-stage larvae were able to produce patent infections in guinea pigs.


Comparative efficacy of fenbendazole, dichlorvos, and levamisole HCI against gastrointestinal nematodes of pigs. Forty-two weanling pigs raised under similar management conditions were used to compare the effectiveness of fenbendazole, dichlorvos, and levamisole HCl against Oesophagostomum dentatum, O. quadrispinulatum, Ascaris suum, Trichuris suis, Hyostrongylus rubidus, and Strongyloides ransomi. All three drugs were given in the feed. Eleven pigs served as unmedicated controls; 11 pigs received fenbendazole (3 mg/kg) on days 1, 2, and 3; 10 pigs received dichlorvos (17 mg/kg) on day 3; and 10 pigs received levamisole HCl (8 mg/kg) on day 3. Fecal specimens from all 11 pigs were collected before and after anthelmintic treatment and examined for nematode eggs. All pigs were killed on day 7, and residual nematodes were counted. The calculated efficacies against the above species, respectively, were: fenbendazole, 99.9, 100, 92.4, 66.0, 99.9, and 0%; dichlorvos, 99.4, 99.9, 100, 99.9, 99.9, and 86.9%; levamisole HCl, 97.1, 99.7, 97.9, 26.1, 94.4, and 99.9%.


Trial of avermectin B1a, mebendazole and melarsoprol against pre-cardiac Dirofilaria immitis in the ferret (Mustela putorius furo). Avermectin B1a was found active against the pre-cardiac stage of Dirofilaria immitis in ferrets. The drug was given orally, at 0.2 mg/kg, on days 38--42 of infection. At necropsy, 5 1/2 months after inoculation, worms were almost totally absent from the hearts of these ferrets. The efficacy of melarsoprol against developing Dirofilaria, which has been demonstrated in dogs by other workers, was demonstrated in ferrets given oral doses, at 100 mg/kg, on days 38--42 of infection. The reported efficacy of mebendazole was not evident in the ferret host in this study, probably because the treatment (100 mg/kg, orally, on days 38--42) was shorter and later than that reported for dogs.


Sleeping sickness: in vitro cultivation of Trypanosoma brucei from the salivary glands of Glossina morsitans. Two strains of Trypanosoma brucei were propagated from the salivary glands of 5 Glossina morsitans for more than 200 days on a bovine embryonic spleen feeder layer using buffered RPMI 1640 medium supplemented with 20% bovine fetal serum. In the first 2 to 3 weeks of cultivation the density of parasites in the salivary glands and culture medium remained constant probably because of defective binary fission. The parasites were infective to rodents only on days 17 and 25. Electron microscopic examination of the parasites on 6 different occasions revealed that they were similar to the immature metatrypomastigotes of T. brucei described in the salivary glands of infected tsetse flies.


Immunoconglutinin associated with nonspecific acquired resistance in malaria, babesiosis, and other anemia-inducing infections. Rats recovered from infectious anemias had an acquired nonspecific resistance. Recovery from trypanosomal and babesial infections enhanced the resistance to infections with filterable rat infectious anemia (RIA) agent, and recovery from RIA made rats more resistant to plasmodial, babesial and trypanosomal infections. The resistance was manifested after challenge by reduced parasitemia accompanied by significant anemia, which became evident 2 or 3 days earlier in recovered rats than in controls. Mortality of the recovered rats was less than that of the controls. Immunoconglutinin (IK) was detected with high titers in animals during the acute stage of each infection and remained present with lower titers after recovery. After the recovered rats were challenged with a heterologous agent, the existing IK titers became elevated earlier and usually were higher than those of the controls. However, the infections also stimulated production of cold-active hemagglutinin (CAH). It was therefore not clear that the resistance could be attributed to IK. The nature of antigen-antibody complexes that may have fixed complement and stimulate IK is discussed. However, a specific complex was not implicated.


Isospora neorivolta SP. N. from the domestic dog. The endogenous development of canine Isospora rivolta (Mahrt, J Protozool 14: 754--759, 1967) was compared with the development of I. ohioensis (Dubey, Parasitology, 1978, In press) in intestines of dogs. A new name, Isospora neorivolta, is proposed for the canine I. rivolta because of developmental differences from I. ohioensis. The major difference between these 2 coccidia is their site of development. Isospora neorivolta develops predominantly in the lamina propria of the posterior half of the small intestine, whereas I. ohioensis develops only in the epithelium and infection occurs throughout the small intestine. Additional information on the development of I. neorivolta in dogs is given.


Structure and composition of the oocyst wall of Eimeria tenella. Oocyst walls were purified from unsporulated oocysts of Eimeria tenella. Analysis of the purified material indicated a composition of 67% peptide, 14% lipid, and 19% carbohydrate. The likely physical arrangement of the components places the lipid in a 10 nm thick outer layer, covering a 90 nm thick layer of glycoprotein. The protein component of the structure was dissociated using thiol reagents under denaturing conditions, and was shown to consist of a repeating subunit of approximately 10,000 daltons. The results suggest an explanation for the physical and mechanical resistance of the oocyst wall, as well as possible mechanisms for excystation of sporulated oocysts.


Quasilistrophorus microticolus gen. n. et sp. n. (Acari: Listrophoridae) from North American microtine rodents. The authors describe a new genus and a new species Quasilistrophorus microticolus (Acari: Listrophoridae) from Arborimus from Oregon and Synaptomys from Indiana.


Normal development of Schistosomatium douthitti in the snail Lymnaea catascopium. Schistosomatium douthitti miracidia are ingested by Lymnaea catascopium snails and penetrate the host's esophageal wall. Mother sporocysts develop adjacent to the esophagus and salivary glands. The increase greatly in size, become irregular in shape, and contain daughter sporocysts by 8 days. Development of daughter sporocysts is synchronous; most are released from mother sporocysts 16--20 days postexposure. Mother sporocysts then collapse, but may persist for the life of the infected snail. Some daughter sporocysts travel to the digestive gland via the arterial system; others traverse the connective tissue separating cephalopedal and visceral sinuses to reach the digestive gland. Cercarial embryo production begins while daughter sporocysts are still within mother sporocysts, and may continue for over 400 days. Once released from daughter sporocysts, cercariae move from the visceral sinus to the visceral vein and are carried into the mantle where they rupture the ventral mantle epithelium and escape from the molluscan host.


Studies on putative adult worm-derived vaccines and adjuvants for protection against Schistosoma mansoni infection in mice. Intraperitoneal transfer of viable adult worms of Schistosoma mansoni did not confer protection against a challenge infection to recipient mice. Antigens of schistosome origin were evaluated for their ability, with and without concomitantly administered nonspecific adjuvants, to stimulate protective immunity against S. mansoni. Freshly perfused ground worms or a putative membrane antigen extracted with 0.5 M KC1 from adult worms, when injected together with Corynebacterium parvum (or in a single experiment with poly [A : U]), resulted in a significant reduction in worm burden of a challenge infection with S. mansoni as compared with that of untreated controls. The membrane antigen was maintained carefully at low temperatures in buffers capable of retarding enzymatic degradation while it was being prepared.


Effects of stressful conditions on the development and movement of reproductive cells in Schistosoma japonicum. Adult S. japonicum exposed to 3H-thymidine to label reproductive cells were cultured in vitro, maintained intraperitoneally, or transplanted as unisexual infections to hamsters. Daily samples were taken, processed for autoradiography, and observed for abnormal morphological and developmental characteristics. By day 5 of in vitro culture in Medium 199 and calf serum, all worms were dead. The vitelline system was the most sensitive to culture conditions and labeled vitelline cells never moved from the gland area. No labeled sperm were produced by males and evidence of deterioration of the testes was apparent by day 2. Degenerative changes of the ovary were the last to appear, on day 3. Most adults transplanted to the peritoneal cavity of hamsters were dead by day 3, but some lived for 6 days. No movement or development of reproductive cells was detected in these worms. An intense cellular reaction directed against the tegument was observed as early as day 1. Males transplanted in groups to the hepatic portal system were maintained normally in vivo and produced labeled sperm in 6 days. Females handled similarly showed degenerative changes in their genitalia by day 2, but most were alive after 6 days.


The life cycle of Paragonimus kellicotti in cats. Migration and development of Paragonimus kellicotti were studied in cats killed between 1 and 265 days after feeding 15--20 metacercariae from the hearts of naturally infected crayfish. Metacercariae excysted in the intestine and appeared in the peritoneal cavity within 24 hr. Some young flukes penetrated the diaphragm and migrated to the pleural cavity during the first week, but the majority penetrated the pleura between 10 and 14 days. No flukes were found in the pleural cavity after 23 days postinfection. By 4 weeks postinfection, the flukes were well established within lung parenchyma, mainly in the right caudal lobe, where most of their growth occurred. Eggs first were seen in flukes on the 34th day postinfection and in feces 2 days later. Estimated daily ova production ranged from 1,000 to 2,000 eggs/fluke/day.


Subacute sclerosing panencephalitis: clinicopathological study of the eyes. This paper described the clinicopathological findings in a patient who died of subacute sclerosing panencephalitis. During his seven-month hospitalization, we had the opportunity to study the evolution of the disease and especially the variability of the ocular findings. The patient was presenting with a right exotropia and later developed chorioretinal changes in the fundus. The pathological examinations of both eyes revealed undescribed details, mostly in the anterior segments of the eyes, namely lacy vacuolization of the pigment epithelium of the iris, vacuolization of the nonpigmentary ciliary epithelium, and proliferation of the ciliary pigment epithelium.


Ocular findings in a patient with Kugelberg-Welander syndrome: a case report. A four-year-old female child with Kugelberg-Welander syndrome has been presented. She demonstrated ptosis, exotropia, and decreased vision with unilateral high myopia. Unlike the Werdnig-Hoffman type of spinal muscular dystrophy Kugelberg-Welander disease has a protracted, somewhat benign course, necessitating proper evaluation and care of the ocular problems of these patients. The most common among these problems are the presence of severe to moderate ptosis and strabismus which appears usually to be an exotropia.


Free floating pigment cyst of the anterior chamber ten years after miotic therapy. A free-floating pigment cyst has been present in the anterior chamber of the eye of a 14-year-old patient with numerous pigment nodules on the border of both pupils for about ten years. As a small child this patient has been treated very successfully with miotics for accommodative esotropia.


Congenital mobile vitreous cyst.

Congenital mobile vitreous cyst. A case of a mobile vitreous cyst occurring in an asymptomatic five-year-old child is presented. A review of the literature shows this to be an uncommon finding best explained as a remnant of the primary vitreous. We believe our patient in this case to be the youngest reported, and supports the congenital, nonpathologic nature of the cyst.


Orbital hemangiopericytoma: a report of a three-year-old child. A case of orbital hemangiopericytoma is described in a three-year-old child. Its clinical and microscopic differentiating features from other ocular and orbital tumors is discussed.


The lactate dehydrogenase isoenzyme pattern in the overacting inferior oblique muscle. The lactate dehydrogenase (LDH) isoenzyme pattern in normal eye muscles of fetuses, children, and adults in overacting inferior oblique muscles of children was studied and compared. No significant differences were found between LDH isoenzyme activity in the horizontal and vertical recti. Isoenzyme fractions, by percentage, were distributed in these muscles in the order of III greater than IV greater than II greater than V greater than I. A significant difference, however, was noted between the LDH isoenzyme patterns of the inferior oblique muscle in normal adults and children. The percentages were in the orders of III greater than II greater than IV greater than V greater than I, and III greater than IV greater than II greater than V greater than I, respectively. The isoenzyme pattern in the overacting inferior oblique muscles of children was in the order of III greather than II greater than IV greater than V greater than I, identical to that of the adult control group. In addition, the overacting inferior oblique muscle of the children contained more H than M subunit than did the rectus muscle or the normal inferior oblique muscle of children by comparison.


Refraction in premature babies: a prospective study. Refraction in 67 premature babies was examined and followed during seven years. There was continuous changing of refraction towards emmetropia in all refraction groups. Fifty-four percent of myopic eyes remained myopic at the age of seven years but in all the eyes myopia was of lower degree than at birth. In our series there was no relationship between myopia and RLF.


Congenital Horner's syndrome and thoracic neuroblastoma. A two-month-old girl presented with a right Horner's syndrome as the only manifestation of a primary thoracic neuroblastoma. The early diagnosis of this condition allows a cure rate approaching 100 percent. Ophthalmologists should exclude thoracic neuroblastoma in children with Horner's syndrome.


Congenital hereditary sex-linked retinoschisis. A case of juvenile idiopathic sex-linked retinoschisis in a six-month-old child was followed for seven years. The familiar occurrence in males was in agreement with the sex-linked inheritance. The appearance at an early age in the left eye confirmed the congenital nature of the disease and the possibility that the ophthalmoscopic features might be present at birth, at least monocularly. In the right eye the ophthalmoscopial normaility of the vitreous as well as the early and severe abnormality of the electroretinographic findings (normal "a" wave, microvolted "b" photopic wave, extinct "b" scotopic wave and presence of only the first wavelet of the oscillatory potentials) at the initial stage of maculopathy induced the author to suppose that there might be primarily a tapeto-retinal heredodegeneration and that the pseudocystic degeneration of the inner layers could be a secondary manifestation of the disease.


Simultaneous 4-muscle surgery in V-esotropia. Simultaneous, bilateral and symmetrical surgery was performed on 60 patients with V-esotropia. The results following one surgical procedure were evaluated. The patients were subdivided into three equal groups. A bilateral recession of the medial recti was performed in all three groups. In the first two groups a weakening of both inferior obliques, either by recession or by myectomy at insertion, was performed. In the third group only horizontal muscle surgery was done. Satisfactory results were achieved in 48 out of 60 patients following one surgical procedure. Consecutive esotropia was present in eight and exotropia in four patients. In cases of V-esotropia with marked overaction of both inferior obliques, a simultaneous 4-muscle surgery is recommended in order to minimize the number of surgical procedures.


An expedient lid retracter.

An expedient lid retracter. An expedient lid retractor may be fashioned from a paper clip.


A new approach to ocular moisture chambers. A new approach is presented to the problem of moisture chamber spectacles for the treatment of the dry eye. This moisture chamber relies on soft polyurethane sidewalls, form fitting and flanged to avoid pressure at right angles to the skin surface. The result is a comfortable moisture chamber which has been used successfully by an eight-year-old patient for nine months. This has allowed the child to return to school with best visual acuity (aphakic) without a single recurrence of corneal erosion.