Computed tomography and ultrasonography in the evaluation of the retroperitoneum in patients with malignant ascites. The computed tomographic (CT) body scans of 59 patients and ultrasonograms of 31 patients, all with malignant disease, were reviewed to determine the effect of ascites on the ability to image the retroperitoneum. In 95% of cases evaluated by CT, the retroperitoneal structures were well seen. In 35% of the cases evaluated by ultrasonography, the retroperitoneum was completely obscured by bowel gas and partially obscured in an additional 55%. As a result of this study, it is felt that CT should be the procedure of choice when a thorough evaluation of the retroperitoneum is necessary in patients with large amounts of abdominal ascites.


Contrast computed tomography in the diagnosis of acute cholecystitis. Computed tomography (CT) has the ability to detect small variations in tissue density. Meglumine diatrizoate was given intravenously to four patients with clinical acute cholecystitis as part of the CT scanning procedure. The enhancement of the thick gallbladder wall, together with an enlarged gallbladder and the presence of stones, confirmed the diagnosis of acute cholecystitis. Our present experience indicates that, after contrast medium administration, CT has a distinct place in the assessment of acute inflammation of the gallbladder.


CT studies of the liver in vitro: a report on 82 cases with pathological correlation. Eighty-two liver specimens were studied by both computed tomography (CT) and pathological examination with serial sectioning. In vitro CT studies showed low density structures within 57 normal livers to be due to portal and hepatic vessels but not to bile ducts. A liver with a minimum of 70% fatty infiltration could be diagnosed correctly on CT. Concerning the presence or absence of circumscribed liver disease, sensitivity was 80% and specificity was 84%. With respect to the total number of space occupying liver lesions (n = 364 in 18 specimens), sensitivity was 72%. The smallest metastases detectable on CT were 0.5 cm in diameter, but CT disclosed focal lesions of this small size in only 15% of the cases. In contrast to previously reported in vivo CT studies, metastases were often found to be of higher density than normal liver tissue in vitro.


Pectus excavatum deformities simulating mediastinal masses. Three patients with various pectus excavatum deformities in whom radiographic findings suggested hilar and mediastinal masses are presented. Computed tomography of the chest yielded valuable diagnostic information and made it possible to exclude the existence of these masses. Compression deformity of the heart and great vessels by the pectus deformity is the most likely explanation for these findings.


Demonstration of the pericardium and pericardial effusion by computed tomography. Characteristic computed tomographic findings were present in two patients with confirmed pericardial effusion. A review of 30 chest scans without evidence of heart disease showed that the pericardium can be seen in the majority of cases.


Computed tomographic and angiographic demonstration of gastroduodenal artery pseudoaneurysm in a pancreatic pseudocyst. The complementary use of computed tomography and angiography in two patients with bleeding gastroduodenal artery pseudoaneurysm associated with pancreatic pseudocyst is presented.


Computed tomography of the gastrointestinal tract: lesion recognition and pitfalls. Abnormalities in the gastrointestinal tract will be found on computed tomography (CT) scans performed for other indications if they are carefully searched for. This potential will increase as CT is used earlier in the investigation of suspected abnormalities of the pancreas. retroperitoneum, and liver. Additionally, CT may be valuable in assessing the extent of a known primary lesion of the alimentary tract.


Variation of position of the kidneys and diaphragm in patients undergoing repeated suspension of respiration. The position of the upper poles of the kidneys in relation to the 12th thoracic vertebra was evaluated on each of three nephrograms of 32 cooperative patients undergoing excretory urography during evaluation for hypertension. Mean change in kidney position relative to vertebral position between nephrograms varied from a mean 4.9 mm on films taken during inspiration to 7.7 mm on films obtained in expiration. Diaphragmatic positional changes could be evaluated in 12 patients; mean change in diaphragmatic position be tween nephrogram exposures was 8.0 mm. Considerable variation in diaphragm position does occur during successive breath-holding attempts for cross-sectional imaging.


Applications of perfluorinated compounds as contrast agents in computed tomography. Perfluorohexylbromide, a nonionic and biologically inert radiodense compound, was evaluated as a potential contrast agent. Pulmonary and gastrointestinal administration of the neat liquid form was tested in dogs in conjunction with computed tomographic body scans. Contrast enhancement was demonstrable in one organ, the spleen, within 6 hr of gastrointestinal administration of perfluorohexylbromide.


Hyperperfusion and enhancement in dynamic computed tomography of ischemic stroke patients. The passage of contrast medium was observed using serial computed tomography (CT) in 24 stroke patients. Density--time profiles of various brain regions were plotted. In normal brain tissue, X-ray attenuation showed a maximum increase during the arterial phase (16.4 +/- 11.0%) and was 2.8 +/- 2.2% above control during stable distribution. In hypoperfusion, increase in attenuation was always below 10% in the arterial phase, while hyperperfusion was characterized by an attenuation increase of 25 to 70%. Enhancement was defined by a density increase of 16.8 +/- 14.8% and a tissue/blood ratio between 7 and 60%. An attempt was made to establish a relationship between the serial CT pattern and the prognosis. Enhancement tended to indicate severe morphological changes followed by permanent neurological deficit, whereas hyperperfusion was generally an indicator of probably recovery.


Fluid--fluid level in cystic cerebral metastatic melanoma. Two cases of cystic metastatic melanoma are presented. The only reliable computed tomography sign of a true cystic lesion is the presence of an interface, such as between blood and tumor fluid. Differentiation of cystic metastatic melanoma from other cystic lesions of the brain is discussed.


Computed tomography of spinal fractures. Computed tomography (CT) has aided significantly in the diagnosis and management of spinal fractures. The examination is easy, relatively quick, and avoids potentially harmful manipulation. The diagnostic advantages of CT include precise anatomic delineation and indication of extent of fractures, assessment of spinal stenosis, and demonstration of associated peraspinal lesions.


Blurring in tomograms made with x-ray beams of finite width. Tomographic reconstruction has ordinarily assumed that the measurement data can be regarded as line integrals, but the finite width of the X-ray beam invalidates this assumption. The data can however be expressed in the form of integrals over a strip rather than a line. The strip integral kernel is calculated allowing for extended source and detector, as well as for nonuniform photon emission and detector sensitivity. Strip eccentricity, which occurs in practice, is also taken into account. Even if the measurement data were to cover all scanning angles, there would be imperfect reconstruction expressible as a space-variant point spread function deducible from the strip integral kernel. To deal with this it is convenient to introduce the concepts of generalized projection and generalized Radon transform. Point-spread functions are given for cases involving piecewise-uniform symmetrical source distributions and uniform detectors.


Erosion of the scapula by a benign lipoma: computed tomography diagnosis. A lipoma eroding the scapula is diagnosed by computed tomography.


Diagnosis of retro-esophageal right aortic arch by computed tomography. A case of retro-esophageal right aortic arch was clearly demonstrated by computed tomography and confirmed by arch aortography.


Diagnosis of retroperitoneal hemorrhage by serial computed tomography. A case of retroperitoneal hematoma is presented in which the characteristic density changes of the hematoma as seen on serial computed tomography permitted an accurate preoperative diagnosis.


Aberrant thyroid gland demonstrated by computed tomography. Computed tomography (CT) demonstrated high attenuation values consistent with thyroid gland in scans of a patient with tumors in the base of the tongue and anterior median neck. Radioiodine scintigraphy revealed positive uptake in the same areas. This is an indication that CT attenuation values may be useful in the diagnosis of aberrant thyroid gland.


Acute isodense epidural hematoma on computed tomography. Computed tomography (CT) has proven to be invaluable in the diagnosis of craniocerebral injuries. Acute epidural hematomas have been described as having a characteristic appearance on CT of a lenticular shaped area of blood density most commonly situated over the cerebral convexity. This case demonstrates an acute epidural hematoma that is essentially isodense with brain tissue.


Scalp markers for precise craniotomy siting, using computed tomography. A rapid, simple, and inexpensive computed tomographic technique has been developed for marking the scalp and lateral skull radiograph of patients with small cerebral convexity lesions. The more precise localization provided thereby facilitates planning and performance of surgery.


Support and bolusing device for scanning small objects. A versatile bolusing device made of polystyrene is described for scanning small objects in currently available "air gap" computed tomography scanners. The device, consisting of three concentric rings fitted inside one another, allows for artifact-free and reproducible imaging.


Direct sagittal computed tomography of the brain. The first results of a simple method for obtaining direct sagittal computed tomography scans of the brain with a Pfizer 200 FS scanner are presented with a brief discussion of the advantages and applications of this technique.


Basal cell carcinoma--signet ring type. Ultrastructural study. Light microscopic examination of a basalioma (basal cell carcinoma) revealed unusual keratinizing cells resembling signet ring cells with pink cytoplasmic inclusions. Ultrastructurally the inclusions consisted of filamentous masses encircled by abundant tonofilaments giving a striking picture of abnormal individual tumor cell keratinization.


Giant cells in male pattern alopecia: a histologic marker and pathogenetic clue. Twenty-one of 65 (31%) biopsy specimens from patients with male pattern alopecia demonstrated the presence of individually displaced multinucleate giant cells without a significant concomitant cellular infiltrate. This finding was absent in a diverse group of other forms of alopecia. Whether individually displaced multinucleate cells are a useful histologic marker for diagnosing early stages of androgenetic alopecia remains to be determined.


Pagetoid reticulosis (Woringer-Kolopp disease). Two patients with solitary lesions of pagetoid reticulosis are presented. A third case with disseminated lesions and similar microscopic detail is also reported. Lighg microscopic findings include an abnornal cell infiltrate confined to the epidermis and distributed diffusely in a pagetoid pattern. In ultrathin sections, the abnormal cells are seen to have an abundant cytoplasm with numerous organelles and a convoluted nucleus, often with a prominent nucleolus. The nature of the abnormal cells is discussed. The infiltrate is differentiated from that of mycosis fungoides.


Biopsies of the Janeway lesion of infective endocarditis. Janeway lesions in three patients with infective endocarditis caused by Staphylococcus aureus were biopsied. Two taken before therapy, showed evidence of suppuration and microabscesses. The other lesion which developed while the patient was on appropriate therapy, showed minimal inflammatory reaction.


Solitary actinic porokeratosis.

Solitary actinic porokeratosis. An 83-year-old man experienced abrupt onset of a solitary lesion of porokeratosis on his bald, actinically damaged scalp. The features in this case are unusual and represent another point in the broad spectrum of lesions characterized by the cornoid lamella of porokeratosis.


Pityriasis rosea in a patient with epidermolysis bullosa dystrophica. A patient with clinical and histologic features of epidermolysis bullosa dystrophica-recessive (EBD-R) developed superimposed clinical lesions of pityriasis rosea (PR). Electron microscopy showed distinct "blebbing" of basal cells at the basement membrane zone in clinically normal skin of a non-predilected area, as well as in scarred skin from a predilected area and a lesion of PR. An increased susceptibility of the basement membrane zone to proteolytic enzymes is suggested as a possible hypothesis to explain these observations.


Multiple keratoacanthomas and squamous cell carcinomas occurring at psoriatic treatment sites. A report on four patients with psoriasis who have developed multiple keratoacanthomas and squamous cell carcinoma at the treatment sites is presented. Two other reports have appeared in the literature which link the development of keratoacanthoma with psoriasis and pustular psoriasis. Although a number of etiologic factors have been suspected for the development of these new growths, this presentation will further assess the specific roles that treatment measures may have played in these cases. Furthermore, the significance of impaired cellular immune defense mechanisms will be discussed.


A tridimensional view of intradermal nevi as revealed by scanning electron microscopy. When scanning electron microscopy (SEM) was applied to the study of intradermal nevi, interesting tridimensional features were recognized. The free surface of the lesions showed ruffled keratinized cells. "Normal" hairs as well as "corkscrew" hairs emerged from the follicular openings. Nevus cells were either round or elongated and surrounded by connective tissue fibers.


Clinical and pathological correlation of malignant melanoma. We have attempted to review virtually all forms of cutaneous and mucocutaneous melanomas. Superficial spreading, lentigo maligna and nodular melanomas have been more thoroughly investigated and documented in previous studies. Lentigo maligna melanoma appears to have a longer duration and better prognosis than SSM or NM. The overall prognosis probably correlates better with the anatomic level and thickness of invasion than with type (Clark et al. 1975, Breslow 1970, 1975). It appears that certain pitfalls exist in either method of assessing prognosis, and it is recommended that both methods be applied in evaluating a malignant melanocytic lesion when feasible. With regard to in situ melanoma or Level I melanoma, it is our experience that such lesions can achieve a 100% cure rate when completely excised. Hence, we prefer to call such lesions severely atypical melanocytic hyperplasia, and thus avoid labeling these patients with a malignant diagnosis. The most difficult histologic challenge in diagnosing a lesion of malignant melanoma is the Spitz nevus. The pathologist should never be biased by the age of the patient, for a serious mistake can arise. We have seen a case of nodular melanoma in a 13-year-old girl diagnosed as Spitz nevus only to be followed by a lymph node metastasis years later. Other examples of histologic differential diagnoses of malignant melanomas include, for example, halo nevus, soft tissue sarcoma, squamous cell carcinoma with spindle cell proliferation, Paget's disease of metastatic carcinoma, (for example, from the breast). Therefore, the approach to the diagnosis of malignant melanoma necessitates an evaluation of both clinical and pathological features. Histologic study must encompass both the pattern of growth and cellular cytologic detail for successful interpretation.


Immune derangement in patients with malignant melanoma. The interaction between immune system and growing tumor can be expressed differently at different stages of the disease. This presentation covers three facets of these reactions in melanoma patients. A. The Primary Tumor. Time-lapse cinematography, with an analysis of lymphocyte movement demonstrated positive and negative chemotaxis against tumor tissues which correlated with their histological presence or absence within the primary tumor. B. The Regional Lymph Nodes. Histological examination of regional lymph nodes showed an increase in germinal center activity and B cell number, with a decrease in sinus histiocytosis and monocyte count as the tumor progressively invaded the node. This correlated with the elution studies, wherein the antimembrane antibody decreased and the anti-cytoplasmic antibody increased during the same period of progression. C. Humoral Immunity and Metastasis. Clinical metastasis heralded the decrease of anti-membrane antibodies with a rise in anti-immunoglobulins, especially anti-idiotypic antibodies and immune complexes containing tumor-directed antibody and either antigen or anti-immunoglobulin. This triad of anti-immunoglobulin, immune complexes and anergy as seen in other diseases with persistent antigenic stimulation, results in abnormal regulation and derangement.


Prognostic factors in the treatment of cutaneous melanoma. The incidence of metastasis in cutaneous melanoma is proportional to maximal tumor thickness. The relationship is linear for extremity melanoma but not for tumors from all body sites, probably due to intrinsic differences in tumors from different sites. The level of invasion of the tumor is an indirect measure of tumor thickness and is not as accurate in predicting metastases because of the marked variation in thickness within each level. The implications of these observations for the treatment of melanoma are discussed.


Surgical management of melanoma.

Surgical management of melanoma. Traditionally, melanoma has been considered by surgeons to be a highly lethal malignancy, always requiring a radical surgical approach for optimal chance of cure. Yet melanoma patients who are now being referred for treatment frequently have small early lesions, and surgeons should develop a flexible attitude about management, limiting the size of their excisions and deferring node dissections in many early cases. An aggressive, radical approach remains appropriate for large lesions, progressively enlarging nodes and locally recurrent but not disseminated disease.


Aggressive biologic behavior of basal- and squamous-cell cancers in patients with chronic lymphocytic leukemia or chronic lymphocytic lymphoma. Three basal- and four squamous-cell carcinomas in seven patients with chronic lymphocytic leukemia or chronic lymphocytic lymphoma recurred repeatedly after conventional treatment, and grew to large sizes. The squamous-cell carcinomas metastasized in all four of the patients so afflicted. Absolute numbers of circulating T lymphocytes were normal in the seven patients, but they had cutaneous anergy to intradermal tests with common antigens and to dinitrochlorobenzene. The following recommendations for management of cutaneous carcinomas in patients with malignant lymphomatoses are made: 1) closer surveillance than for patients with cutaneous cancers but without malignant lymphomatoses, 2) early treatment of actinic keratoses to prevent possible transformation to malignancy, and 3) microscopically controlled excision of basal- or squamous-cell carcinomas larger than 1 cm in diameter.


Wound healing: a review. III. Nutritional factors affecting wound healing. Wound healing proceeds more efficiently and quickly in well-nourished individuals who are in good general health at the time that they have to undergo surgery. Per contra, individuals who are malnourished and chronically ill heal less well and are in general at greater risk of complications during and after surgery. For the latter, elective surgery may be deferred until nutritional improvement is attained, but for emergency or urgent operations, institution of measures promoting good nutrition has to be concurrent with necessitous surgery and continued postoperatively. In this paper, the importance to wound healing of proteins, carbohydrates, fats, vitamins, and trace elements and minerals is reviewed.


Special techniques of hair transplantation by fusiform grafts and flaps of many types. There are more and better ways of transplanting scalp hair than merely by punch grafts. Techniques of transplantation by fusiform grafts and flaps are briefly described, advantages are stated, and results are illustrated.


Basal-cell carcinoma in the youthful: report of a case in a young woman. A rare instance of the spontaneous development of a basal-cell carcinoma in front of the tragus in a young person of 19 years and its management are described.


Presidential address. The advancement of the knowledge and practice of allergy. State and local allergy societies have appeared in response to pressures created by progressive specialization, increase in knowledge, and need for cost control within the field of allergy and clinical immunology. They provide a mechanism whereby allergists and immunologists with many different interests and functions can work in an integrated and cooperative manner to provide, in a cost-effective fashion, adequate patient care, teaching, and research in allergy and immunology for the geographic area. Maximum effectiveness requires close liaison with medical schools, state medical societies, national allergy organizations, and the local chapter of the Asthma and Allergy Foundation of America. Their structure should permit frequent close communication between members in various fields of allergy and clinical immunology, and the organization of committees that can accomplish the hard work of ensuring care for the disadvantaged patient, time and money for research, cost control, identification and rehabilitation of the poorly functioning allergists, continuing education for physician and patient, and all of the other tasks that make the practice of allergy and clinical immunology such a wonderful and absorbing way of life.


Further characterization and biologic activity of ragweed antigen--induced neutrophil chemotactic activity in man. We have previously described the appearance in serum of increased neutrophil chemotactic activity (NCA) during bronchospasm induced by inhalation of ragweed antigen in ragweed-sensitive subjects. This NCA is non-complement derived, appears within 1 min after antigen inhalation, and is not seen after methacholine-induced bronchospasm. This article describes further characterization of this chemotactic activity and correlation with in vivo leukocytosis. NCA consistently eluted in the void volume (fraction I) after Sephadex G-150 chromatography of patient serum obtained 10 min postchallenge. Fraction I contained 94% of the NCA of postchallenge whole serum. Both postchallenge whole serum and fraction I deactivated neutrophils to autologous chemoattractants and complement-derived chemotactic factors, but not serum-independent chemotactic factors. NCA was chemotactic for neither human nor guinea pig eosinophils, nor for human mononuclear cells. A significant increase of circulating neutrophils was seen only after antigen-induced bronchospasm and correlated with the increase in NCA. Thus, NCA represents another inflammatory mediator of probable mast cell origin that may explain, at least partially, the accumulation of neutrophils observed in the peripheral blood, skin, and bronchial wall after immediate hypersensitivity reactions.


Allergenicity and lymphocyte-stimulating property of rice protein. Two protein fractions of rice, grain, glutelin and globulin, were prepared by dilute alkali and salt extraction, respectively. The globulin fraction was separated into G1-1, G1-2, and G1-3 fractions by Sephadex G-200 column chromatography. The allergenic activities and lymphocyte-stimulating properties of these fractions were investigated by the radioallergosorbent test (RAST) with sera from 6 individuals who showed immediate skin reaction to soluble rice extract and by 3H-thymidine incorporation tests with 5 subjects with indurated skin reaction of delayed onset. All fractions were found to be reactive with specific IgE antibody, and G1-1 and G-2 revealed lymphocyte-stimulating activity. RAST inhibition revealed considerable cross-reactivity of IgE antibody with the glutelin and globulin fractions. When the glutelin and globulin fractions were heated at 60 degrees C for 1 hr, 100 degrees C for 2 min, or 100 degrees C for 10 min, RAST activities were reduced to 40%-70% of native. On the other hand, lymphocyte-stimulating activities of the globulin fraction heated at 60 degrees C for 1 hr or 100 degrees C for 2 min were enhanced up to 6 times of native activities, while those of identically treated glutelin fractions remained unchanged.


The seasonal variation in a population of house dust mites in a North American city. Mattress dust collected at monthly intervals for 2 1/2 yr was examined for mites. Both Dermatophagoides pteronyssinus and D. farinae were found. There was a significant association between the presence of live mites and the relative humidity (RH): Live mites were seen only when the RH had been greater than or equal to 50% for at least part of every day during the month of collection. There was a seasonal variation in that live mites were found only in the warmer months and not in the winter. However, the peak in the mite population was consistent neither for month nor for numbers: In 1977 a slight peak in mite numbers occurred in October, while in 1978 the peak was higher and occurred in July. Use of data from previously published studies to preduct mite levels may therefore be misleading.


Acute allergic reaction after composite pollen ingestion. Three patients are presented who ingested a health food known as "bee pollen" and who experienced an immediate allergic reaction. Examination revealed that the bee pollen contained dandelion pollen, which belongs to the Compositae family as does ragweed. In vivo and in vitro studies demonstrated that the patients were sensitive to several Compositae family members, rather than to insect-derived antigens. In addition, radioallergosorbent inhibition studies confirmed the suspected cross-reactivity between the health food and Compositae pollens. This study indicates that atopic individuals may experience anaphylaxis from ingestion of antigens in certain food stuffs that cross-react with pollens to which they are sensitive.


Clinical and biochemical effects of impeded androgen (oxymetholone) therapy of hereditary angioedema. Daily therapy and alternate-day therapy with the attenuated androgen oxymetholone were compared in patients with hereditary angioedema (HAE). Fifteen of 16 patients who experienced at least monthly attacks of HAE without treatment were asymptomatic on administration of 5 mg oxymetholene daily. When 13 of the patients who had been maintained asymptomatically on 5 mg oxymetholone daily were advanced to a treatment schedule of 5 mg every other day, seven attacks occurred during a cummulative 50 mo of therapy. The adverse effects that occurred with daily oxymetholone therapy largely subsided when the patients received alternate-day therapy, while a significant mean rise in C4 protein and function occurred only on daily therapy. Statistically significant mean increases in serum levels of C1INH occurred with daily therapy and were maintained with alternate-day therapy. Clinical benefit can be obtained with a treatment program that does not produce a statistically significant rise in C4 protein or function and does not raise C1INH to the lower limit of normal. The finding that alternate-day therapy diminished the side effects of the drug while affording a substantial reduction in the incidence and severity of attacks indicates the feasibility of this therapeutic approach.


Prostaglandin generation by human and guinea pig lung tissue: comparison of parenchymal and airway responses. Anaphylaxis of human lung is accompanied by the synthesis of prostaglandins (PG), including PGF2 alpha and PGE. In an analysis of the tissue source of these prostaglandins, parenchymal preparations of both human and guinea pig (GP) lungs were compared. Peripheral, relatively airway-free preparations of human lung generate PGF2 alpha and PGE in response to histamine and 2-methylhistamine, on H1 agonist, but not to dimaprit, an H2 agonist. GP parenchymal preparations respond in a similar fashion. Stimulation of these same preparations with KCl or carbachol caused no increase in the synthesis of either PG. In human airway preparations all three agonists (histamine, KCl, and carbachol) caused the selective generation of PGE. However, stimulation of GP airway preparations with the agonists caused the production of both PGE and PGF2 alpha. These data indicate that (1) human and GP peripheral lung tissues respond to H1, but not H2, stimulation with the generation of PGF2 alpha and PGE; (2) these parenchymal responses are specific and may not be attributed to muscle contraction; and (3) stimulation of muscle contraction in human airway preparations results in the selective generation of PGE while GP airways produce both PGE and PGF2 alpha.


Binding of immunoglobulin and activation of complement by asbestos fibers. Asbestos fibers adsorbed IgG from whole human serum in amounts comparable to that taken up by crystals of calcium pyrophosphate or hydroxyapatite, but less than that adsorbed by crystals of monosodium urate monohydrate. Chrysotile asbestos was much more active in binding IgG than was amphibole asbestos. The electrophoretic mobility of adsorbed IgG was a function of the surface charge of the crystal studied. Negatively charged fibers adsorbed cationic IgG, and positively charged fibers adsorbed anionic IgG. Complement activation by asbestos, as judged by electrophoretic conversion of C3, was similar for all fiber types tested. Properdin factor B was also activated in the presence of asbestos. Activation of both properdin factor B and C3 was only partially inhibited by ethylene glycol tetraacetic acid, demonstrating that activation was occurring through both the classical and alternative pathways.


Effect of unsaturated fats and cholesterol on serum and fecal lipids. A study of healthy middle-aged men. Modification of the Western diet, with an intake of 2,500 kcal per day and a decrease in cholesterol and fat intake to 33 per cent of calories with a P:S of 0.40, failed to alter serum lipids significantly. Evidence suggested that increasing the daily intake of cholesterol resulted in deposition in the body tissues. However, when the fatty acid composition and the P:S ratio of dietary fat were adjusted, lower serum lipids and a compensatory increase in fecal sterols occurred when cholesterol was added to the diet. Changes in serum lipoproteins in the subjects fed a "prudent" or a common diet indicate an increase in the proportion of HDL-cholesterol which may be beneficial in reducing coronary heart disease. Evidence suggests that, in absence of caloric excess, lowering of serum lipids and increased removal of fecal sterols is possible on a prudent diet without major modification of the customary foods, but that a high P:S ratio is required.


Food habit changes of Chinese persons living in Lincoln, Nebraska. Qualitative and quantitative changes in food habits of Chinese persons living in Lincoln, Nebraska, were evaluated. Findings indicated that these people do have a flexible attitude toward foods. Incorporation of American foods into their diet and a decreased consumption of Chinese foods showed that a continuous process of food-habit changing is occurring in this group. In particular, more American foods have been incorporated in their breakfast and lunch patterns, while for the dinner meal, the more traditional Chinese foods continue to be eaten. Factors related to the ease of adaptation to American food were investigated, and possible implications are suggested.


Ascorbic acid status of children with developmental disabilities. Ascorbic acid status of thirty-nine white children with developmental disabilities, ages three to nineteen years, is reported. Mean daily ascorbic acid intakes were calculated from three-day food records. Biochemical assessment consisted of fasting serum levels and a 6-hr. load test. Nine children served as a control group for the load test only. Mean dietary intakes for the vitamin were 204 per cent of the allowance. The mean serum ascorbic acid value was 1.3 mg. per deciliter. Only two children had levels at the unacceptable deficient level. Following load tests, ten children were identified as low excretors (less than 17 per cent), nine were moderate excretors (17 to 23 per cent), and the rest were high excretors (above 23 per cent). All of the normal children were high excretors. Two of three children with low ascorbic acid intakes (below 66 per cent of the recommended allowance) were verified as deficient by their fasting serum levels and urinary recovery after a load.


Continuing education needs as perceived by dietetic practitioners. Educational needs of dietitians were identified by 232 practitioners in Ohio by means of a self-administered questionnaire. Three major knowledge areas--managerial science, nutritional care science, and behavioral, communicative, and socio-cultural science--were covered in 109 questions. The respondents perceived a need for more professional knowledge than for behavioral, communicative, and socio-cultural sciences. Greater need was expressed for skills in technical and human ability than for skills in conceptual ability, and generally for nutritional knowledge rather than application. The findings could form the basis for continuing education programs.


Work-related values and satisfactions. A cross-occupational analysis of professionals vs. non-professionals in hospital dietetic services. Job satisfaction and work values of hospital dietitians were studied and compared with those of non-professional hospital foodservice personnel. The instrument was distributed to dietitians in nine Midwestern states. Dietitians had higher job satisfaction than foodservice employees on four components: The work itself, supervision, earnings, and compatibility with co-workers. Satisfaction increased with years in the profession, with directors of dietetics being more satisfied than staff dietitians. On the work value measures, dietitians scored higher on drive, ambition, and self-concept, whereas non-professional employees tended to attribute success to luck and "knowing the right people."


Diet therapy in gastrointestinal disease: a commentary. Dietary regimens in gastrointestinal disease can be divided into two categories: First, those of proven value include: (a) Disaccharide elimination for disaccharidase deficiency and exclusion of monosaccharides for sugar malabsorption; (b) gluten-free diet for celiac/sprue; (c) elimination of certain allergens because of food allergies; (d) protein restriction for portal systemic encephalopathy; (e) low-carbohydrate diet for dumping syndrome; (f) low-fiber diet for diarrheal syndromes; and (g) low-fat diet for steatorrhea. Second, controversial diets include a bland diet for acid-peptic disorders, a high-fiber diet for colonic disorders, and a low-fat diet for gallbladder disease. It is important to separate facts from fancy in the dietary management of patients with gastrointestinal disease and base the recommendations for a particular diet on available objective evidence, not on traditional or fashionable trends.


Diagnosis of pupillary anomalies.

Diagnosis of pupillary anomalies. Lesions of the afferent, intercalated, efferent (parasympathetic), and cervical sympathetic arms of the pupillary pathway each tend to produce rather distinctive clinical signs. Sophisticated equipment generally is not needed to define the probable basis for anisocoria and/or disordered pupillary function. Diagnosis of the more common anomalies of the pupil usually can be made from observations obtained using only a penlight, occluder, slit lamp biomicroscope, and a few diagnostic pharmaceutical agents. This paper has been written as a guide to recognition of pupillary signs and as an aid to the practitioner who must differentiate among those that mandate immediate referral, those which require careful analysis on a less urgent basis, and those that can be regarded, for all practical purposes, as benign.


Contrast sensitivity functions for clinical optometry. Contrast sensitivity functions (CSF) provide a better measure of visual function than traditional acuity tests. The use of CSFs with cataract and contact lens patients as well as with patients suspected to have glaucoma or retrobulbar neuritis is discussed. Various methods for determining the CSF are discussed, with the conclusion that the newly developed Arden plates are best for use in clinical practice.


The amblyopic eye: is it downtrodden or just lazy? Over the past decade or two considerable information has been compiled about the functioning of individual cells in mammalian visual cortex. Out of this data is developing a clearer understanding of the etiology of amblyopia. And with this clearer understanding is coming the development of new ideas for clinical practice in the prevention, treatment, and cure of amblyopia. While the leap from single-cell neurophysiology lab to optometric practice office seems like a huge one, the gap is narrowing; and taking the leap promises to provide a rich pay-off for vision health care.


The distance of rock test -- a preliminary report. This paper is a preliminary report describing the development of a new clinical test for measuring the response time of the visual system to shift from distance to near and back to distance to a given discriminatory task. The new test is called Distance rock (Drk) and is calibrated in cycles per minute. Data from college students and survey results from 591 school children from the first to sixth grades were used to develop these preliminary results. Change in response time covariant with grade level was demonstrated which indicates this test may become clinically important for developmental vision.


Effects of training on near-far response time as measured by the distance rock test. The practice effects of specific visual training were demonstrated on twelve seventh grade students and seven optometry students using a distance rock test to measure distance-near response time. Fourteen practice sessions resulted in a 49% improvement for seventh grade students (range 15 to 78%) and a 40% improvement in cycles per minute for college students (range 24 to 64%). Errors were corresponding reduced as cycles per minute were increased.


Some reflections on boredom.

Some reflections on boredom. Boredom is a complex mental phenomenon, incorporating both affective and cognitive components, which cannot be understood within the confines of conflict theory alone. The paucity of fantasy in the bored person may reflect a developmental ego defect as well as, or instead of, the commonly-cited impulse-defense conflicts. The need for externally-supplied stimulation characteristic of persons with a field-dependent cognitive style, and/or characterological passivity may be among the significant predisposing factors for the development of boredom, and phase-specific factors may encourage its occurrence at particular periods of life. Boredom in the analyst, too, is multiply determined; the analytic situation itself contains features that contribute to it.


Methodological problems in the psychoanalytic interpretation of literature: a review of studies on Sophocles' Antigone. Through a critical review of several studies dealing with Sophocles' drama, the Antigone, I have explored some of the prominent methodological problems encountered in the psychoanalytic interpretation of literature. Foremost among these is the inherent difficulty that the interpretation of literature is unable to benefit from the process of the analytic situation. Divorced from the realities of the therapeutic process, the drama itself is often used to corroborate an author's theoretical bias or to advance some special interest, with consequent distortion or blurring of the text. Although data about the artist's life and sociocultural environment may be of crucial significance, it is the text itself that must be the ultimate object of study. Through a re-examination of the Antigone as an aesthetic totality I have sketched out what appears to be an alternative manner of approaching the drama, and suggested that works of art reach us on both unconscious and conscious levels. I have stressed the need to analyze our emotional response to a work as affording a valuable source of insight into the work itself. Throughout, I have drawn attention to the need for greater scholarly rigor and the value of interdisciplinary collaboration. An open recognition of the problems in the psychoanalytic study of literature should serve to minimize dilettantism and raise the level of scholarship.


[Comparison of the action of an impeded estrogen, frideron, and of estradiol on the seminal vesicles and on the weight of the testicles and accessory sex glands in the rat. II]. We have undertaken a comparative study on the effects of estradiol and of an impeded estrogen, zeranol, in the prepubescent Wistar male rat. Both had an inhibitory effect on the secretion of F.S.H. in the spermatogenesis test. Nine injections of estradiol or nine ingestions of zeranol had a restraining effect with a dose of 0.5 microgram of estradiol or of 500 micrograms of zeranol (for 100 g of body weight). With some animals, spermatogenesis is interrupted and the weight of the testicles decreased; the treatment is more active with stronger doses: 2 micrograms of estradiol interrupted spermatogenesis in 10 rats out of 11, 1.000 microgram of zeranol interrupted it in 10 rats out of 13. A weak dose of either estrogen (0.05 microgram of estradiol or 20 micrograms of zeranol) stimulated the growth of the seminal vesicles, the prostate gland and the preputial glands. Strong doses decrease the weight of the preputial glands, and even more the weight of the prostate gland (10 micrograms of estradiol, 1.000 microgram of zeranol). They are ineffective on the seminal vesicles. The effects of 2 micrograms of estradiol on the testicles and the accessory sexual glands are completely inhibited by the simultaneous administration of 2 U.I. of P.M.S. rich in FSH.


[The prognostic value of raised uric acid in the blood in arterial hypertension in pregnancy. 58 cases (author's transl)]. The authors have carried out research in 58 cases to see whether the findings of high uric acid levels in the blood are of prognostic value in all cases of arterial hypertension in pregnancy whatever the aetiology. The material studied consisted of 30 true cases of toxaemia of pregnancy, 13 cases of recurrent toxaemia and 15 cases of the vasculo-renal syndrome on top of the pre-existing pathological condition. In 37 cases where the blood uric acid level was lower than 300 micromoles there were only 4 minor complications. Serious complications were found in 6 cases in which the patients had a blood uric acid level highthan 480 micromoles. This study confirms the prognostic value of blood uric acid levels. The estimation of these levels, however, seems to be of less value in making a differential diagnosis between the various kinds of toxaemia and hypertension found in pregnant women due to different aetiologies.


[The correlation between sonar morphological measurements and plasma levels of oestradiol and oestriol in early pregnancy (author's transl)]. 53 cases of pregnancy complicated by bleeding between the 7th and 16th week have been studied by repeated estimations of non-conjugated plasma oestradiol and oestriol carried out at the same time as ultrasound morphological measurements were performed. 24 pregnancies went on to term while 29 met with the loss of the fetus. In each case where the outcome was favourable the plasma oestriol and oestradiol levels were comparable to those found in 95 control pregnant women whose pregnancies progressed normally. In 26 cases where the outcome was unfavourable the levels were too low and corresponded to an ultrasound picture that was abnormal or revealed absence of heart beat. In 3 cases the first levels of oestradiol and oestriol seemed to be normal. Later, when failure of growth of the embryo and absence of heart beat were found, a considerable drop in the levels of oestradiol and of oestriol in the blood was also revealed. This study shows a good correlation between hormone levels and ultrasound findings in pregnancies complicated by bleeding. All the same, the prognostic value of hormone measurements as compared with ultrasound measurements has not yet been established, and needs analysis of a far greater number of cases of a similar type.


[A contribution to the study of ovarian cancer during pregnancy and the puerperium. 3 case histories (author's transl)]. The authors have seen three cancers out of 27 organic ovarian tumours which were diagnosed and operated on during pregnancy and the puerperium in 16790 deliveries. They recall the circumstances under which the condition was discovered and the difficulties in diagnosing it. They point out particularly the value of ultrasound and frozen section histological examination. They point out the therapeutic problems which are often of a dramatic nature because of the association of the two conditions and the prognosis which in turn depends mainly on the stage of the lesion and the operability of the tumour. Poor maternal prognosis in cases of ovarian cancer is an indication for operation before the 20th week of pregnancy of all tumours of the ovary which have been clinically diagnosed and confirmed by ultrasound.


[Celioscopic sterilizations with Yoon rings. 300 cases. Immediate complications, effectiveness and reversibility]. The authors report on a series of 370 sterilisations using Yoon's rings, of which 300 were carried out laparoscopically. They confirm the efficiency of the method and its safety because there was only minimal operative morbidity. On the other hand this technique offers the possibilities of reversal of sterilisation in such a way that it should be the preferred method to be used systematically when a young woman is being sterilised.


Histopathology of experimental Schistosoma incognitum infection in mice following exposure to normal and irradiated cercariae. The tissue reactions in mice, experimentally infected with normal and irradiated cercariae of S. incognitum were studied. The lesions observed in the skin, liver, lungs and the intestine of mice infected with normal cercariae are briefly described, and compared with those observed with cercariae irradiated at 3000 r of gamma rays. In general, the reactions in mice exposed to normal cercariae were more intense than in those infected with irradiated cercariae. The severity of the reactions appeared largely due to the deposition of eggs in the tissues of the mice infected with normal cercariae. The experimental evidence suggested that most of the flukes from the irradiated cercariae are destroyed in the liver by tissue reaction.


Host-parasite relationship of Angiostrongylus cantonensis. 1. Intracranial transplantation into various hosts. Various stages of Angiostrongylus cantonensis recovered from the brain of experimentally infected mice were transplanted intracranially into rats. Third and fourth-stage worms recovered 2--7 days postinfection were able to develop normally after transplantation into recipient rats. The fifth-stage worm obtained 14--15 days postinfection would enter the brain tissue of rats but died shortly afterwards. However, the same stage of worms recovered from rats, after a similar transplantation, were found to develop normally in the recipient animal. Young fifth-stage worms, from the subarachnoid space of rats, which were ready for the pulmonary migration were also transplanted into rabbits but the worms failed to reach the lungs. In the control rat-to-rat transplantation, the worms successfully completed the pulmonary migration. The morphogenesis and initial growth rate of A. cantonensis were similar in both mice and rats but in the former host the worms started to grow at a markedly slower rate after the last moult and gradually degenerated.


A new technique for the recovery of Toxocara eggs from soil. A new flotation technique for the extraction of Toxocara eggs from soil has been devised. It has a fairly high recovery efficiency for Toxocara eggs, can be used for replicated quantitative experiments, and may also be used for recovery of other ascarid eggs from soil.


Prevalence of Toxocara spp. eggs in some public grounds and highway rest areas in Kansas. Out of a total of 282 soil samples obtained from public areas, 58 samples contained Toxocara spp. eggs. This gave an overall prevalence of 20.6%. Highway rest areas were contaminated and childrens sand boxes had the highest percentage of recovery of all.


Preliminary survey of Capillaria hepatica (Bancroft, 1893) in Malaysia. The prevalence of Capillaria hepatica (Bancroft, 1893) infection in a total of 2324 rats trapped from 25 localities in West Malaysia was 15.5%. Infection rates in males (16.0%) and females (15.1%) are similar. A significantly higher percentage of adults (18.1%) than young (7.7%) was infected. Capillaria hepatica infection rates among urban (0.7%) and jungle (0.0%) rats was very low as compared to field rats (17.7%) trapped from agricultural areas such as oil palm estates and rice growing areas. Prevalence of C. hepatica infection in rats is not evenly distributed throughout West Malaysia. There seem to be localised foci of infection. In some areas as many as 77.8% of the adult rats are found to be infected while in other areas the same species of rats are found free of infection.


Effect of diethylcarbamazine on the concentration of Onchocerca volvulus microfilariae in hydrocoele fluid and urine. The effect of graded doses of diethylcarbamazine on the concentration of microfilariae in the hydrocoele fluid, urine and skin of patients suffering from onchocerciasis was studied. The results showed that a significant number of microfilariae migrated into hydrocoele fluid and urine immediately after the drug was given and thereafter returned to pre-treatment levels rather more quickly in the former than the latter. The increase was found to be roughly directly proportional to the intensity of infection in the skin. By contrast the skin concentration of microfilariae fell sharply after treatment and remained significantly lower than pre-treatment levels for over four weeks. The potential use to which these observations could be put with respect to clinical screening of drugs in onchocerciasis is discussed.


The occurrence and distribution of H-2 antigens on mouse intestinal epithelial cells. This report describes an immunoferritin labeling study of mouse H-2 histocompatibility antigens on epithelial cells dissociated from the small intestine by EDTA and trypsin. Before cell dissociation, the intestine was prefixed in paraformaldehyde or periodate-lysine-paraformaldehyde in order to preserve the shape of the cells and to immobilize H-2 antigens in their native positions. The results demonstrated the presence of H-2 antigens on the lateral and basal cell membranes at about the same high density that was observed at the surface of mouse monocytes. No H-2 antigens could be detected at the apical surface of dissociated or undissociated epithelial cells. It is unlikely that the fuzzy coat masked H-2 antigens at the apical surface because it was essentially absent from the apical membranes of dissociated cells. These observations extend our knowledge of the cellular distribution of transplantation antigens, and provide further evidence of a discontinuity in the expression of membrane components at the junctional complex of epithelial cells.


Cytochemical demonstration of adenylate cyclase in cardiac muscle: effect of dimethyl sulfoxide. Adenylate cyclase (AC) activity was evaluated after perfusion fixation of rat and dog myocardium with 4% paraformaldehyde (PFA), 2% glutaraldehyde (GA) or a combination of both, in cacodylate buffer. Dimethyl sulfoxide (DMSO) was added to the fixatives and its effect on the preservation of cell organelles and enzyme activity was determined. Adenylate cyclase activity was preserved best after fixation with 4% paraformaldehyde but this fixative did not provide for optimal maintenance of structure. Prefixation with 2% glutaraldehyde and 5% dimethyl sulfoxide provided the most effective preservation of both structural and enzymatic integrity. Precipitation of lead diphosphoimide was the morphologic indicator of sites of adenylate cyclase activity. The most intense precipitate was in the lumen of junctional sarcoplasmic reticulum in close contact with T-tubules and in subsarcolemmal cisternae. Evidence of activity was also seen on the intracellular aspect of the sarcolemmal membrane and in the nexus segment of the intercalated discs. Alloxan was effective as an inhibitor of adenylate cyclase activity only if the concentration of the activating substance sodium fluoride (NaF) was 20 mM or lower.


Effect of rabbit strain on activity level and cytotoxicity of serum complement. III. Comparison of four tumor target cells. Serum samples from about 10 males and 10 females from each of 15 genetically defined strains of rabbits and from one hybrid were tested as sources of complement for the microtiter lymphocytotoxicity test using tumor cells from SaI-A, 6C3HED-A, BW5147, and L-cells as target cells. The tumor cells were tested with appropriate H-2 antisera. Results indicated strain differences particularly evident when the target cells were eithter 6C3HED-A or L-cells. BW5147 worked well with most all strains and SaI-A was extremely demanding of all strains of rabbits. However, strains IIIC/J, IIIVO/J and the F1 hybrid between them were still among the six best strains when tested against the tumor cells as they were when tested against the lymph nodes in previously published data. Strain WH/J which carries the gene, ha, for hereditary lymphosarcoma, proved to be a good complement source with SaI-A and 6C3HED-A, both sarcoma in nature. However, it was not a good complement source with BW5147, a lymphatic leukemia, or L-cells. This is possible evidence for a common tumor antigen associated with lymphosarcoma.


On the immunocytochemical localization of the vasoactive intestinal polypeptide. The distribution of vasoactive intestinal polypeptide (VIP) immunoreactive nerves and endocrine cells in the gastrointestinal tract and pancreas of a number of mammalian and submammalian species has been examined in order to throw light on the exact localization of this peptide. Seven out of 8 VIP antisera demonstrated numerous nerve fibers in the gut, whereas one antiserum (TR2) revealed only scattered, few nerve fibers. The distribution of endocrine cells demonstrated by the different VIP antisera varied considerably. Thus, some antisera demonstrated only endocrine cells in the feline antrum, others only colonic endocrine cells and still others only endocrine cells of the upper gut and pancreas. The variability in staining pattern of endocrine cells as well as recent radioimmunological data makes it opportune to suggest that true VIP is a neuronal peptide and that endocrine cells store peptides resembling, but not being identical with, VIP (VIPoids).


Reproduction and teratogenic studies of 5-thio-D-glucose in mice. Under the conditions of the present study, 5-thio-D-glucose was found to be an effective and useful reversible male contraceptive. Treatment of male mice with 5-thio, administered intraperitoneally or orally at 40 or 60 mg/kg for 28 to 35 days produced germinal cell degeneration and complete inhibition of spermatogenesis in the seminiferous tubules. These treatment regimens also resulted in complete sterility in males lasting for several weeks. Resumption of sperm development and fertility occurred with 5 to 6 weeks after treatment was discontinued. The Leydig cell population, Sertoli cells, and spermatogonia apparently were not affected and male libido was not impaired. There was no evidence of embryotoxic or teratogenic effect in litters of pregnant females treated orally with 5-thio on days 6--12 of gestation.


Repeated epilation: a genetic epidermal syndrome in mice. Repeated epilation is an autosomal semidominant mutation located on chromosome 4 of the house mouse. Heterozygotes for Er show irregular hairloss. Homozygotes die immediately after birth from acute respiratory distress and exhibit an hypoplastic epidermal syndrome associated with morphological modifications of the oral cavity and of the limbs.


Immunohistochemical characterization of monolayer cell cultures of embryonic chicken pancreas and measurement of somatostatin release. Monolayer cell cultures of embryonic chicken pancreas contain functionally active insulin, glucagon and somatostatin-containing cells as evidenced by immunohistochemical and radioimmunoassay techniques. Hormone release is in relation to the number of each cell type present and responds to known specific secretory stimuli. The relatively high numbers of D-cells and amounts of immunoreactive somatostatin released by this preparation makes this system a suitable model for studies of somatostatin function and secretion.


Immunocytochemical localization of hepatic legandin and Z protein utilizing frozen sections for light and electron microscopy. Ligandin (glutathione-s-transferase) and Z protein are soluble hepatocellular proteins that are involved in the transfer of organic ions, including bilirubin and some hormones and carcinogens from the plasma to the liver. The intracellular distribution of ligandin and Z protein was studied by applying the peroxidase-antiperoxidase procedure of L. A. Sternberger (Immunocytochemistry, Prentice Hall Inc., 1974) to paraffin sections and free-floating 10-micrometers frozen sections that were processed for both light and electron microscopy. Ligandin and Z protein were localized to the cytosol of hepatocytes in association with smooth endoplasmic reticulum (SER), but no reaction product was present between cisternae of rough endoplasmic reticulum. Penetration of reagents was enhanced in 10-micrometers frozen sections and the preservation of subcellular structures was equivalent to thicker, unfrozen sections.


Morphometrical analysis of an ultrahistochemical demonstration of nonspecific esterases in hepatocytes of mice after fructose overload. Changes in ultrastructural distribution patterns of nonspecific esterases (E.C. 3.1.19) are described quantitatively by means of morphometry. Esterases were demonstrated with O-acetyl-8-hydroxyquinoline (Q-O-2) and S-acetyl-8-mercaptoquinoline in livers of normally and exclusively fructose-fed mice. Conditions are discussed, under which the quantification of the ultrastructural products of enzyme histochemical reactions may be possible. Smooth endoplasmic reticulum and rough endoplasmic reticulum exhibit no alteration in enzyme distribution with both substrates since the enzyme-occupied proportion of each compartment remains the same despite an overall decrease of both compartments. Likewise an increase of O-acetyl-8-hydroxyquinoline-esterase at fat droplets corresponds to the increase in total surface of the fat. S-acetyl-8-mercaptoquinoline-positive fat surface however reveals an increase far beyond that of the total fat surface. The results support the hypothesis that a variety of esterases with different substrate spectra are present at the subcellular level in different cell compartments.


Tissue fixation by osmium tetroxide. A possible role for proteins. The osmiophilia, under the conditions of normal tissue fixation, of the histidine, lysine, tryptophan, cysteine and methionine side chain of proteins is suggested by in vitro studies on blocked amino acids representative of such protein side chains, and the chemical nature of the reaction products elucidated. The chemical feasibility of inter- or intramolecular cross-linking of protein by OsO4 at these and other sites is demonstrated, as in the cross-linking of protein with unsaturated lipids such as methyl oleate, methyl linoleate and linolenate, and cholesteryl acetate. The relevance of these results to the process of tissue fixation by OsO4 is discussed.


The use of lectins and cholera toxin for the detection of surface carbohydrates of cultured neurons and neuroblastoma. Conjugates of horseradish peroxidase with the lectins ricin (d-galactose), wheat germ agglutinin (N-acetylglucosamine), phytohemagglutinin (N-acetylgalactosamine), and with cholera toxin (GM1 ganglioside) were used for a cytochemical detection of corresponding termin al carbohydrates, or glycolipids on cell surfaces of cultured neurons and neuroblastoma cells. Cells were labeled at 4 degrees C with the above ligands and their adsorptive endocytosis was studied after incubations at 37 degrees C in a medium free of ligand. Peroxidase was detected by the method of Graham and Karnovsky (J. Histochem. Cytochem. 14:291, 1966). Lectins and cholera toxin underwent endocytosis in cisternae and vesicles of GERL (Golgi-Endoplasmic Reticulum-Lysosome). We suggest that GERL is the primary ercipieint of adsorptively endocytosed plasma membrane "receptor"-ligand complexes which are thus degraded or possibly reutilized (recycling). Wheat germ agglutinin-horseradish peroxidase conjugates used in vivo for studies of retrograde axonal transport were significantly more sensitive than free horseradish peroxidase.


Subcellular localization of complex carbohydrates in rat macrophages and monocytes. Methods for visualization of complex carbohydrates ultrastructurally were employed to study specific organelles of the rat monocyte and macrophage. Vicinal glycols of glycoconjugates were demonstrated with the periodic acid-thiocarbohydrazide-silver proteinate (PA-TCH-SP) postembedding sequence and acid groups were delineated by the dialyzed iron (DI) and high iron diamine (HID) preembedding techniques. Lysosomal bodies were generally found reactive with all three methods, although those of monocytes from the bone marrow and peripheral blood were notably lacking in acidic groups. The Golgi complex was consistently PA-TCH-SP-reactive, as were associated vesicles and occasional cisternal expansions, possibly related to GERL. Numerous cytoplasmic vesicles and small granulated structures and cisternae of the rough endoplasmic reticulum were also PA-TCH-SP-reactive.


Cytochemical characterization of secretory and cell surface glycoconjugates by light and electron microscopy. Lectin methods have increased the capacity for histochemical characterization and differentiation of glycoproteins and have demonstrated, for example, greater reactivity of gastrointestinal than of respiratory tract secretions with the periodate-concanavalin A-horseradish peroxidase method for localizing mannose-rich glycoprotein. Application of a battery of ultrastructural cytochemical methods with specificity for the constituents characteristically present in the complex carbohydrates provides knowledge of the distribution of the various recognizable types of glycoconjugates in tissues and cells showing, for example, marked differences in glycoconjugates of the apical compared with the basolateral plasmalemma in a given cell type and differences between apical plasmalemmas or basement membranes of different cell types. Such information raises questions as to the biologic significance of the different complex carbohydrates in various sites and, hopefully, will lead to a clearer understanding of their physiologic roles.


A mammary gland whole mount technique that preserves cell fine structure for electron miscroscopy. A mammary gland whole mount technique has been developed that preserves cell fine structure and makes it possible to also examine the preparations by electron microscopy. The glands are placed on glass microscope slides, fixed in a paraformaldehyde-glutaraldehyde mixture, defatted in acetone, stained with 0.5% methylene blue (or trypan blue) in saline, and dehydrated in ethanol. They are evaluated and photographed in 100% ethanol. Then specific areas (i.e. containing small growths, tumors, or other lesions) are selected, excised and prepared for electroscopy. The ultrastructural preservation is good, organelles are evident and there is no observable dye precipitate. The only unusual finding is that cell membranes display a "negative" image.


Complement-mediated binding of immunoglobulins to some endocrine cells of the pancreas and gut. Unspecific binding of immunoglobulins to gastrin, somatostain and glucagon cells of the gastrointestinal mucosa or pancreas has been found to occur through a nonantigen-antibody mechanism mediated by the C14 fraction of complement. The phenomenon represents an important drawback in hormone immunohistochemistry, which can be overcome by using complement deprived, highly dilute anti-hormone sera.


Innervation of the pancreas by substance P, enkephalin, vasoactive intestinal polypeptide and gastrin/CCK immunoractive nerves. Immunocytochemical studies habe shown that many peptides which profoundly affect the endocrine and exocrine functions of the pancreas are localized to neurons. In the cat, such peptidergic nerves appear to innervate ganglia, islets and blood vessels of the pancreas, whereas their contributions to exocrine cells are minor. Our studies suggest that pancreatic ganglia represent one major site of action of the peptides and that, in addition, nerves containing the vasoactive intestinal polypeptide and gastrin/CCK-related peptides profoundly affect pancreatic blood flow and insulin secretion, respectively.


Ultrastructural localization of neurophysin-like immunoreactivity in the rat posterior pituitary. An alternative method using frozen-dried tissue fixed with OsO4 vapor. Electron microscopic identification of elements containing neurophysin-like immunoreactivity can be accomplished in rat posterior pituitary that has been frozen-dried and fixed with OsO4 vapor. Alternating serial ultrathin sections are placed on grids and glass slides. The sections on the slides are stained for neurophysin using immunofluorescence histochemistry, and the resultant images are superimposed on electron micrographs from the adjacent sections. The method provides several advantages for the localization of neuropeptide immunoreactivity in nervous tissue.


The subcommissural organ of submammalian vertebrates: a histochemical study. Since morphological data do not allow to draw conclusions concerning the phyletic evolution of the subcommissural organ (SCO), a "metabolic" criterion is considered. Histoenzymology permits a comparison of metabolic activity in the subcommissural organ and that found within the ependyma. During the course of phyletic evolution, one notes various changes. Indeed, in lower vertebrates, the SCO presents a greater degree of enzyme activity than the ependyma while in birds the ependyma demonstrates a more intense activity than the SCO. The results are also compared with those previously reported in reptiles and mammals. In all vertebrates, glucid catabolism seems predominent in this areas.


Post-hatching growth and allometry of the teleost brain. The growth of the brain in the rainbow trout follows an S curve: E = 0.04 t3 + 0.26 t2 - 0.06 t + 0.04 with t (time) in days and E (brain weight) in mg. The growth of the brain, relative to the body, can be given, after longarithmic transformation, by: Y = 0.011 + 0.835 X - 0.047 X2 where Y is log brain weight and X log body weight. This formula is consistent with that of every species after necessary changes of origin. The coefficients of allometry corresponding to this curve vary from 0.788 (body weight from 0.01 to 0.1 g) to 0.226 (body weight from 10 to 100 kg), the most common values varying between 0.507 (body weight from 10 to 100 g) and 0.414 (body weight from 100 g to 1 kg).


Comparative study on the teleostean optic tectum. Lamination and cytoarchitecture. Seventy-five species of teleosts were studied by a modified Bodian and the Golgi-Cox method to clarify certain relationship between habits and laminar formation in the optic tectum. The optic tectum of all species studied was divided into four layers (SM, 20 + SFGS, SGC + SAC and SPV) depending upon fiber connections with other areas, and the relative thickness of each layer was measured. All animals were classified into 8 groups (thick SM, thin SM, thick SO + SFGS, thin SO + SFGS, thick SGC + SAC, thick SPV, thin SPV and standard) based on relative thickness of each layer. The thick SM group has the large torus longitudinalis. The SO + SFGS group comprises diurnal, especially visually active fishes. As relative thickness of surface layers (SM and SO + SFGS) increases, the absolute value of whole layers becomes large. Aniamls with large relative thickness of the deepest layer (SPV) show the thin optic tectum. Seven types of cells, (a) pyramidal cell, (b) fusiform cell, (c) periventricular cell, (d) pyriform cell, (e) large multipolar cell, (f) horizontal cell and (g) small multipolar cell, were classified in Golgi-Cox preparations, and the extent of dendritic arborization was compared among the groups in relation to the thickness of each layer. Dendritis of pyramidal, fusiform and preiventricular neurons show varoius extents of arborization in proportion to thickness of layers where branch out. Other types of neuron do not conspicously vary in different groups. Animals belonging to the thick SPV group show poor dendritic arborization in all types of cells. These results were discussed from the ecological standpoint.


[Enzymatic chemoarchitecture of the isocortex of humans (area 10 of Brodmann)]. The distributions of some oxidoreductases, esterases and phosphatases were investigated in the area 10 (lobus frontalis cerebri) of old human brains by means of histoenzymatic methods. It was possible to observe a different spread of enzymatic activites of hydrolases and oxidoreductases in the several layers of human frontal cortex. The microphotometrical gradation of oxidoreductases was identical with the results of the most mammal brains with the exception of the alpha-glycerophosphate dehydrogenase. The enzyme products of this oxidoreductase show a increase in the lamina 6 and in the subcortex. The cause of the culmination is not jet clear.


Catecholamine activity and infectious disease episodes. The profile of 3-hydroxy-4-methoxy mandelic acid (VMA) excretion was studied in relation to reported acute infectious disease episodes. Daily VMA excretion levels and symptom reports were analyzed for a group of 47 volunteers over a four-week period. Results showed a tendency for elevated VMA levels to occur with greater frequency within three days prior to the onset of symptoms. These findings are interpreted as suggesting that elevated levels of catecholamine activity may increase susceptibility to disease by interfering with the immune response, and in the presence of an agent lead to an infectious disease episode.


Life change events and mental illness: an overview. The use of recent life change measurement in the lives of persons developing mental disorders parallels the measurement of risk factors by epidemiologists to understand disease distribution. Examples are given of these parallels, along with critical commentary on methodological issues in life changes research. The principal studies documenting the association of recent life change and depression, schizophrenia, and neurosis are reviewed. Recent life changes appear to be an important element in explaining illness onset. Future advances in the area of life change and illness await the development of reliable and valid measures of an individual's stress tolerance characteristics, such as social support systems, psychological defenses, coping capabilities, and illness behavior tendencies.


Life event classifications and the event-illness relationship. Several theoretically important and distinct categories of life change are found in most life event scales. These categories can be organized in terms of at least three dimensions: the person's control over the event, the desirability of the event, and whether or not the independent variable of the event is confounded with the dependent variable of illness. It is important to separate conceptually and, to the extent possible, to distinguish empirically among events according to these dimensions, because several different models of the event-illness relationship are implied when events from several categories are combined. A secondary analysis of  recently published data shows that the kinds of events associated with illness are undesirable events within the subject's control. It may not be necessary to consider these dimensions in predicting illness, but the prevention and understanding of illness are furthered by their consideration.


Dietary fibre and the irritable bowel syndrome. The dietary fibre intake of 25 patients with the irritable bowel syndrome was assessed by dietary recall over one week for the period before onset of symptoms, at diagnosis and after six months treatment with bran and a fibre-rich diet, and compared with controls matched for age and sex. Mean intake of patients fell from 20.2 g per day before onset of symptoms to 17.8 g at diagnosis (n.s.), when it was significantly less than the controls' intake of 22.6 g (P less than 0.01). The 20 patients who improved with treatment increased their intake from 18.9 g to 24.8 g (P less than 0.02); the five patients who did not improve did not increase their intake significantly (13.5 g to 15.6 g).


Zinc, copper, iron and lead in scalp hair of students and non-student adults in Oxford. Scalp hair samples contributed by 215 students and non-student adults in Oxford were washed, ashed and analysed by atomic absorption spectrophotometry for zinc, iron, copper and lead. The overall results were within the ranges reported from similar investigations carried out elsewhere and are what might be expected with normal, healthy subjects. However, examination of the results for different groups showed some significant differences between levels of the nutrient metals in student and non-student hair. Results for lead indicate a low level of environmental contamination for all subjects.


High-fibre foods: a feasibility study using guar gum. Guar gum at different concentrations was incorporated into foods from six groups to establish some principles to aid the production of high-viscosity therapeutic foods. The amounts of gum that could be incorporated into a food, without major loss of acceptability, were higher in products with low final water content than those with high final water content. The domestic preparation of these recipes should be possible provided that recipe modifications are carefully followed.


Working as an applied nutritionist in Third World development. The nature of development programmes is considered and employment opportunities in the Third World are briefly summarised. The qualities needed for dietetic educational proficiency in an alien culture are discussed. The assessment of cultural influences should be applied to dietetic teaching situations in Britain as well as to overseas work.


Creamatocrit procedure versus triglyceride analysis: a comparison of methods for the determination of human milk fat in epidemiological studies. A comparison is made of triglyceride analysis and the creamatocrit procedure to determine their usefulness as methods for measuring the fat content of human milk. Triglyceride analysis is shown to be the more precise technique but, for use in the field, the creamatocrit method has the advantage of simplicity.


Antibody-mediated immunosuppression of a cytotoxic cell response not involving a simple antigen-masking mechanism. An in vitro cytotoxic cell response against alloantigens was inhibited by antibody directed against the alloantigens and also by anti-trinitrophenyl antibody provided that the allogeneic stimulator cells were modified with trinitrophenyl. Inhibition of an anti-allogeneic cytotoxic cell response against trinitrophenyl-coupled allogeneic stimulator cells by anti-trinitrophenyl antibody is dependent upon the intact Fc portion of inhibitory antibody. The magnitude of the difference between intact and F(ab')2 anti-trinitrophenyl antibody in immunosuppressive activity suggests that the Fc portion emits negative signals rather than simply adding to a steric hindrance effect.


Regulation of contact sensitivity to DNFB in the mouse: effects of adult thymectomy and thymic factor. The contact sensitivity response to DNFB is decreased after adult thymectomy (ATX). This response decreases to 50% of the control response of normal age-matched mice as soon as 3 weeks after ATX and is not further depressed 9 to 16 weeks after ATX. These results suggest that two T cell subsets of different lifespan are involved in the anti-DNFB response. A circulating thymic factor (FTS) is able to restore the contact sensitivity response to DNFB when injected 3 to 9 weeks after ATX but not 16 weeks later. By contrast, FTS has a depressive effect on the contact sensitivity response to DNFB of normal mice through a cyclophosphamide-sensitive T cell subset. These results suggest that FTS regulates DNFB contact sensitivity by acting on a cyclophosphamide-sensitive T cell subset, still present 9 weeks after ATX but absent after 16 weeks. Thus although the T cell defect, causing a depression of the contact sensitivity reaction to DNFB is quantitatively similar 3 and 16 weeks after ATX, its nature is probably different.


Organ and isotype distribution of plasma cells producing specific antibody after oral immunization: evidence for a generalized secretory immune system. Mice were induced to produce IgA antibodies against ferritin after oral immunization. Such antibodies were detected by immunofluorescence in plasma cells in the intestinal mucosa as well as in secretory sites located elsewhere, such as the lactating mammary gland, salivary gland, and respiratory tract. The observation suggested that cells immunized locally via the gut could home to distant secretory sites. To confirm this hypothesis, lymphocyte transfer studies were done with mesenteric node (MN) versus peripheral node (PN) cells from orally immunized donors into nonimmunized recipients. IgA anti-ferritin cells from MN homed to exocrine targets, whereas IgM and IgG anti-ferritin cells homed to PN. The findings overall support the concept of a generalized and interrelated secretory immune system.


Rapid magnetic purification of rosette-forming lymphocytes. High gradient magnetic separation, which as previously been shown effective in extracting erythrocytes from a flowing cell suspension, has been used to separate rosetted and unrosetted human peripheral blood lymphocytes. The hemoglobin in the sheep red cells used to form rosettes was first oxidizied to the paramagnetic methemoglobin form. Samples of 50 x 10(6) lymphocytes could be processed in 10 min under sterile conditions with greater than 90% purity of the rosetted cell fraction and maintenance of T cell function in mixed lymphocyte cultures.


Measurement of cell-mediated inflammation in experimental murine autoimmune encephalomyelitis by radioisotopic labeling. A radioisotopic index test was used to detect that time of onset and intensity of cell-mediated immune inflammation of experimental autoimmune encephalomyelitis (EAE) in mice. Mice were tested at various time intervals after an encephalitogenic immunization with mouse spinal cord to homogenate for delayed-type hypersensitivity (DTH) to myelin basic protein (MBP) by intradermal challenge with antigen in the ear pinna. After 25 hr, the intensity of DTH was measured by 125I-radiometry which depends upon the migration of 125I-UdR radiolabeled mononuclear cells into the antigen depot. Cells reactive to MBP were detected by the ear assay as early as 7 days after the initial encephalitogenic sensitization. The degree of cell-mediated immune inflammation in the brain and spinal cord during the evolution of EAE was also measured by a radioisotopic technique; increased 125I-UdR uptake could be detected in the brain 3 to 4 days before the onset of signs of EAE at days 11 to 12, whereas 125I-UdR in the spinal cord was detected only 1 day before, or concomitant with, the onset of signs of EAE. Both, or concomitant with, the onset of signs of EAE. Both the "ear" and "organ" radiometric index tests are useful in measuring the degree of cell-mediated inflammation in EAE, and supplement routine histopathological and observational assessments.


Genetic control of sensitivity to Moloney leukemia virus in mice. II. Mapping of three resistant genes within the H-2 complex. The level of viremia and the appearance of leukemias were studied after inoculation wtih Moloney leukemia virus (M-MuLV) in different H-2 congenic strains of mice. The viremia was regularly measured on individual mice with a radioimmunoassay of the major internal virion component p30. Three genes within the major histocompatibility complex controlled the level of circulating virus. Two of them, called Rmv.1 and Rmv.2, appear to be located in the I region, respectively, in the IA, and the IC-S or G regions. The third gene, Rmv.3, was mapped to the D end of the complex in the D or T region. Crosses between resistant and sensitive strans demonstrated that the H-2 associated resistance was inherited as a dominant or semi-dominant Mendelian trait. Rmv.1, Rmv.2, and Rmv.3 were shown to complement for resistance in trans when the hybrids between sensitive strains were examined. A good correlation was found between viremia and the appearance of leukemias, the most viremic strains being also the most leukemic. Nevertheless, additional non-H-2 genes must control viremia and/or the appearance of leukemia since, despite high levels of viremia, some sensitive strains do not become leukemic.


Histocompatibilty-linked susceptibility for hepatospleenomegaly in human schistosomiasis mansoni. In schistosomiasis mansoni, the pathogenesis of hepatosplenic disease has been shown to be due primarily to immune mechanisms. The present study was designed to examine the relationship between the development of schistosomal hepatosplenomegaly in Egyptian school children and the HLA antigens. Two groups of schistosome-infected children with similar fecal egg counts were examined: one group (23 children) had no clinically demonstrable hepatosplenomegaly whereas all the children (28) in the second group suffered from liver enlargement. Furthermore, 13 of the 28 individuals in the latter group had splenomegaly as well. Our results show that hepatosplenomegaly was related to the presence of two HLA antigens: HLA AI and B5. The average relative risk of developing hepatomegaly is 29 for HLA AI and 18.9 for 55.6. Furthermore, the severity of hepatomegaly was correlated with the presence of these two HLA antigens. These findings represent a step toward elucidating the factors controlling the pathogenic mechanisms in human schistosomiasis mansoni.


Promonocytes have the functional characteristics of natural killer cells. Promonocytes isolated from a 5-day-old L-fibroblast-conditioned liquid bone marrow culture show strong NK cell cytotoxicity. They kill YAC target cells in a short-term 125IUDR-release assay whereas P815 targets are unaffected. This NK-like cytotoxicity is enhanced in the presence of interferon preparations. Morphologically, these promonocytes resemble a medium size lymphocyte with a high nucleus to cytoplasma ratio, they are nonadherent, nonphagocytic, and negative in nonspecific esterase staining. Promonocytes are precursor cells from macrophages, which have not yet developed the typical macrophage criteria. Within 24 to 48 hr they mature to adherent macrophages. We have shown previously, that the same promonocytes have the capacity to perform K cell killing of antibody-coated tumor target cells. The cytotoxic effector functions of promonocytes are abolished when the cells are treated with the alloantimacrophage serum Mphi 1.2 plus rabbit C. The relationship or similarity between K cells, NK cells and promonocytes is discussed.


Antibody-dependent cellular cytotoxicity effector cell capability among normal individuals. Nonadherent peripheral blood lymphocytes (PBL) from 110 normal individuals were evaluated for their capability to mediate antibody-dependent cellular cytotoxicity (ADCC) against rabbit antibody-sensitized chicken erythrocytes (CRBC). Titration of PBL against a constant number of chromium-51 labeled CRBC allowed for construction of dose response cytotoxicity curves where percent chromium release was plotted against the number of PBL. From these curves the maximum degree of lymphocyte-mediated cytotoxicity and the number of lymphoid cells required for 50% of the maximum lymphocyte-mediated cytotoxicity were determined. The results suggested that in this system the cytotoxic capability of PBL from normal individuals was independent of the age and sex of the donor. The cytotoxic capability of PBL was also found to be constant in individuals tested sequentially. However, significant differences were found to exist between different individuals in their capability of mediating ADCC in this system.


Tritium (3H) radiolabeling of protein A and antibody to high specific activity: application to cell surface antigen radioimmunoassays. Staphylococcal protein A and several different immunoglobulins have been radiolabeled to high specific activities (greater than 10(6) cpm/microgram) by reductive methylation with tritiated (3H) sodium borohydride. The proteins retain excellent functional and antigenic properties. The utility of these reagents in a variety of assays for cell surface antigens is illustrated. The results indicate that this radiolabeling procedure may become the method of choice for many cell surface and solution immunoassays.


Normal immunosuppressive protein purification and quantitative estimation experiments. An improved method for the preparation and purification of normal immunosuppressive protein (NIP) is described. The purified material has a molecular weight between 10,000 and 25,000. Its biological and serological activity is approximately 10--20 times higher than that of the crude fraction. An antibody to normal immunosuppressive protein prepared in rabbits made the quantitative estimation of NIP by a haemaggluination inhibition test possible. Similarly, a very sensitive assay for the quantitative determination of NIP by its inhibitory effect on the proliferation of EL-4 tumor cells is also described. Eluates prepared from polyacrylamide gels were active in inhibiting EL-4 tumor cell proliferation and neutralized the anti-NIP activity in the haemagglutination inhibition test.


ACDAS: an automated chemotaxis data acquisition system. An automated system (ACDAS) for rapid collection and analysis of data from leading front chemotaxis assays is described. ACDAS automatically computes (1) net cell migration from operator-entered end point signals and (2) means and standard errors of the mean from data sets of user-determined size. ACDAS reduces data collecting and processing time by more than 50% compared to manual methods. Other applications of ACDAS are discussed.


Binding of ovalbumin to mouse spleen cells with and without carbodiimide. We studied the binding of ovalbumin (OVA) to mouse spleen cells. In the presence or absence of carbodiimide (ECDI), uptake increased with greater cell numbers, increasing OVA concentration and increasing time up to 60 min. Between 60 and 210 microgram OVA could be coupled with ECDI to 2 X 10(8) cells. In the absence of ECDI, however, OVA uptake was still appreciable, but appeared to be of low avidity as it did not occur in the presence of competing fetal calf serum. These experiments provide a basis for the use of protein coupled to autologous cells in the induction of immunologic tolerance.


Detection of human histocompatibility (HLA) antigens with an indirect rosette microassay. An indirect rosette assay which utilizes erythrocytes coupled with purified antiimmunoglobulin (Ig) antibodies was modified into a microassay for detecting HLA allo-and xenoantibodies. The test, which is performed in microtiter plates, is specific, reproducible and can handle large numbers of samples. As an inhibition assay the test can detect HLA antibodies even if mixed with antibodies to other cell surface structures. The rosette microassay is at least 10 times more sensitive than the complement-dependent microcytotoxic test and can use target cells which exhibit low viability or abnormal susceptibility to lysis.


A new method for semi-automated quantitation of E-rosettes using a particle size analyser (Coulter Channelyzer). Visual counts of the number of SRBC attached to individual lymphocytes in E-rosette preparations from 3 healthy young adults were made by 3 experienced observers: from these data the size distribution profile of particles in each E-rosette preparation was calculated. In parallel experiments the size distribution profile was measured directly with a particle size analyser (Coulter Counter and Channelyzer): in every case the observed profile lay within the 95% confidence band around the reconstructed profiles. It was concluded that the Coulter Channelyzer profile is an accurate measurement of the E-rosette size distribution and that particle sizing could provide a reasonable basis for semi-automated tests for E-rosettes. A mathematical model has been developed by which the percentage of lymphocytes forming E-rosettes, the distribution of number of attached SRBC and the average avidity of the lymphocyte receptor for SRBC could be deduced from the size-distribution profiles. The method has a high degree of precision, and a good correlation (P less than 0.01) was obtained when the percentage of E-rosettes (defined for this purpose as having three or more attached SRBC) obtained from the new method was compared with results from standard light microscopy.


A simple cytochemical method for distinguishing EAC rosettes formed by lymphocytes and monocytes. A simple cytochemical method for EAC rosettes in suspension is described which allows an easy distinction between rosettes formed by lymphocytes and monocytes. The method is based on the fact that monocytes, in contrast to lymphocytes, possess a specific cytoplasmic esterase.


Induction of specific anti-actin antibodies and their measurement by ELISA technique. Using the ELISA technique we have been able to quantify antibodies directed against actin and to follow the kinetics of antibody production. Specific anti-actin antisera have been raised in rabbits by immunization with chemically modified white muscle rabbit actin. Two or three dinitrophenyl groups linked per actin molecule were sufficient to break natural tolerance, while linkage of three phosphorylcholine groups to actin was not.


An enzyme-linked immunosorbent assay for antibodies to native and denatured DNA. A modification of the enzyme-linked immunosorbent assay (ELISA) is described, that permits determination of antibodies to native DNA (nDNA). The same approach can be used to measure antibodies to denatured DNA (dDNA). Poor binding of nDNA to the polystyrene solid phase has presented difficulties in using the ELISA method for assaying anti-nDNA activity (Engvall, 1976), but we find that precoating of the solid phase with protamine sulfate circumvents this problem. Assays for anti-dDNA are also enhanced by the use of protamine sulfate coated tubes. We have used the ELISA method to assay 15 SLE and 27 non-SLE sera for anti-nDNA and anti-dDNA activity. The results are compared with those obtained using the GF/A glass fiber filter assay, previously described by Lewis et al. (1973).


A radioisotopic technique for measuring the mononuclear inflammatory response in Sindbis virus-induced encephalitis of mice. The mononuclear inflammation occurring in Sindbis virus-induced encephalitis of mice has been measured by means of pulse labelling with [125I]UdR at a defined time after infection. The method should be applicable to other studies of encephalitis and of mononuclear cellular infiltration occurring in other organs as a result of disease or infection.


A new gradient former and a simplified procedure for zonal centrifugation of immune complexes. A new gradient former for production of optimized sucrose gradients for B-XIV zonal rotors is described. Optimized gradients are gradients with an initial shelf to provide capacity and a shape that ensures isokinetic sedimentation conditions. By exhaustive computer calculations it has been found that optimized gradients can be produced by a very simple two-compartment gradient former. The design is given. Moreover, graphs for choice of gradient strength and run duration for preparative and analytical runs of samples containing soluble immune complexes are calculated. The new gradient former allows the use of a very simple procedure for zonal centrifugation.


Radioimmunoassay for pyrazolone derivatives. The determination of pyrazolone derivatives by radioimmunoassay has been reported. Anti-antipyrine antisera were obtained by repeated immunization of rabbits with 4-azoantipyrine-conjugated bovine serum albumin. The level at least as low as 1.0 ng of antipyrine could be detected by this procedure. Various substituents on the carbon 4 position of the pyrazolone ring as well as the lack of methyl group on the nitrogen 2 position decreased the affinity for the antibody, and the antibody showed no cross-reaction with any pyrazolidine derivatives.


Probable EnaEn heterozygotes in two British families. An investigation of the serological and biochemical properties of red cells in two unrelated British families revealed the probable presence of examples of the rare genotype EnaEn. In one family the En-modified red cells carried N-like determinants associated with s. In the other family M-like determinants associated with S were found.


H-2 linked immune response to murine experimental Schistosoma mansoni infections. Mice of two congenic inbred strains C3H/Sn (H-2k) and C3H.B10 (H-2b) were infected with 100 Schistosoma mansoni cercariae. After the infection, the following parameters for the immunological response were studied: worm burden, mortality, antibody titre, spleen index, eosinophilia, delayed type of hypersensitivity and in vitro response to three S. mansoni antigen preparations. No difference in the worm burden and in the in vitro response to the antigen preparations of adult worm antigen, soluble egg antigens and the egg antigen MSA1, was found. The C3H.B10 mice showed a significantly higher mortality, antibody titre and delayed type of hypersensitivity while the C3H/Sn mice showed asignificantly higher spleen index and eosinophilia. This indicates that the H-2 region influences the course of an acute S. mansoni infection, whereas the susceptibility to the infection seems not to be influenced, as is shown by the worm burden.


A statistical analysis of human lymphocyte transformation data. The lymphocytes from 107 maternal-foetal pairs were examined for their in vitro responsiveness, as determined by the incorporation of tritiated thymidine following stimulation with phytohaemagglutinin (PHA), candida, varicella, mumps, streptokinase-streptodornase (SKSD) and tetanus toxoid. The data were collected and analysed in two sequential groups (forty-seven and sixty) in order to determine whether the results were reproducible. The variable chosen for analysis was the difference (d) between the square roots of the isotope incorporation in the stimulated and control cultures because it gave the most symmetrical distribution of the data. The experimental error in the determination of maternal lymphocyte stimulation was 1.4--8.6% and of the foetal lymphocytes, 1.0--16.6%, depending upon the antigen or mitogen and its concentration. The data in the two sets of patients were statistically the same in forty-eight of the fifty-six analyses (fourteen antigen or mitogen concentrations in autologous and AB plasma for maternal and foetal lymphocytes). The statistical limits of the distribution of responses for stimulation or suppression were set by an analysis of variance taking two standard deviations from the mean as the limits. When these limits were translated into stimulation indices, they varied for each antigen or mitogen and for different concentrations of the same antigen. Thus, a detailed statistical analysis of a large volume of lymphocyte transformation data indicates that the technique is reproducible and offers a reliable method for determing when significant differences from control values are present.