A comparison of the scaling of Afro-Americans' life-change events.

Research using the Recent Life Change Questionnaire is being conducted with various ethnic, economic, and cultural groups. The findings of studies using comparable forms have indicated that economic conditions and cultural differences have a minimal effect upon the overall concordant rankings of most groups. In this paper, cultural and economic variables which influence the rankings of poverty-level Afro-Americans are compared with data from a previous study. The significant items related to employment, health, and family problems were found to influence the subject's life conditions, and those related to interpersonal relationships were found to be based on cultural values. The author discusses the importance of recognizing economic and cultural variables which are salient to the measure of life changes by selecting a scoring system which allows for the influence of these variables.


Recent trends in sex mortality differentials in the United States.

Since 1920, American men, to an increasing degree, have experienced higher levels of mortality than American women for virtually all causes of death at almost every age. Recently, several authors have asserted that there is evidence of a change in these trends, caused primarily by rises in the levels of female mortality. Using age-adjusted death rates and data for the most recent years available (1960-1974). This paper shows that most female death rates are either stable or falling, and that the sex mortality differential for all causes except lung cancer is either stable or increasing.


Interaction of task difficulty, activation, and work load.

The performance of 25 subjects in three reaction tasks of different complexity was compared at different activation levels induced by five different work loads on a bicycle ergometer. Heart rate and blood pressure were used as indexes of activation. The results were in agreement with the Yerkes-Dodson law in that the optimal physiological activation level for rapid performance varied with the degree of task difficulty, relatively lower activation being more favorable the more difficult the task.


Isolation of the third component of mouse complement.

The third component of mouse complement has been purified to homogeneity from pseudoglobulin by two chromatographic steps involving sequential cation- and anion-exchange chromatography. Mouse C3 is a beta-glycoprotein of m.w. 210,000 consisting of two nonidentical, disulfidelinked polypeptide chains of m.w. 130,000 and 75,000, respectively. The properties of this molecule and its proteolytic fragments closely resemble those of human C3.


Cuta neous basophil responses in neonatal guinea pigs: active immunization, hapten specific transfer with small amounts of serum, and preferential elicitation with phytohemagglutinin skin testing.

Previous studies have demonstrated a failure to elicit delayed hypersensitivity skin responses in neonatal guinea pigs despite apparent immunologic competence of their lymphocytes and monocytes. The ability of neonatal guinea pigs to manifest cutaneous basophil hypersensitivity (CBH) responses was examined. Neonates were competent to express macroscopic and microscopic aspects of these delayed reactions. Strong cutaneous basophil responses were elicited in newborns (0 to 2 days old) in a hapten-specific manner after intravenous transfer of small amounts of immune serum (0.5 ml) obtained from adult donors. Also, neonatal guinea pigs actively immunized at birth with hapten-carrier conjugates emulsified with incomplete Freund's adjuvant (IFA) and skin tested when 1 week old had 24-hr hapten-specific cutaneous basophil reactions and CBH reactions to the carrier protein as well. Compared with adult CBH reactions, neonatal responses had equal concentrations of basophils, fewer monocuclear cells, less macroscopic erythema, and almost no induration. Hapten-specific CBH reactions also contained significant infiltrates of eosinophils which were more prominent in the ear skin vs flank skin and in neonates vs adults. Immunization with complete Freund's adjuvant (CFA) resulted in a marked difference between adults and neonates; adult PPD reactions were quite indurated and contained many more monoculear cells and few basophils, whereas neonatal PPD reactions were flat, erythematous, nonindurated, and contained relatively few mononuclear cells and more basophils. Thus, neonatal tuberculin reactions elicited by PPD in animals immunized with CFA were examples of CBH. Skin testing nonimmune guinea pigs with phytohemagglutinin (PHA) also revealed marked differences in 24-hr cutaneous reactions between adults and newborns. Adults had indurated and erythematous reactions which contained approximately 20% basophils and 80% mononuclear cells, whereas similar PHA skin tests in newborns elicited small macroscopic reactions, which microscopically showed large infiltrates containing approximately 80% basophils and 20% mononuclear cells. It was concluded that neonatal guinea pigs were not only competent to manifest basophil-containig delayed-type reactions, but that cutaneous basophil responses were preferentially elicited in these animals under a variety of circumstances. These results underline the fact that basophil accumulations are one aspect of delayed skin test responses and that the regulation of the arrival of these cells in neonates is different from that in adult guinea pigs.


Role of the immune response in recovery from Sindbis virus encephalitis in mice.

The role of the immune response in recovery from acute encephalitis was studied by using a neuroadapted strain of Sindbis virus. Intracerebral inoculation of this virus caused fatal disease in weanling mice. Passive transfer of homologous immune serum protected mice, but transfer of immune spleen cells and lymph node cells failed to alter mortality. Transfers were made 24 hr after intracerebral infection of the recipient, when central nervous system infection was established. The protective factor in serum was present 7 days after donor infection, was specific for Sindbis virus, and appeared to be IgG; however, the protection did not correlate with virus-neutralizing activity.


Uncommon Gm phenotypes in sera from neuroblastoma patients.

Gm phenotypes and IgG subclass levels were determined in the sera of 68 patients with neuroblastoma. The frequency of the uncommon phenotypes Gm(a+,f+,g-,b+) and Gm(a+,f+,g+,b-) was found to be significantly higher in the neuroblastoma group than in normal blood donors (p less than 0.001). IgG subclass concentrations in the nine sera with uncommon Gm phenotypes and in the sera of neuroblastoma patients were inconspicuous.


Relationship of cellular proliferation and the generation of cytotoxic cells in an in vitro secondary immune response to syngeneic rat lymphoma cells.

The role of cellular proliferation for the generation of cytotoxic activity in an in vitro secondary immune response to syngeneic lymphoma cells was investigated. Spleen cells from W/Fu rats immunized with the syngeneic (C58NT)D tumor proliferate and generate cytotoxic potential for tumor targets after exposure to mitomycin C-treated (C58NT)D cells in vitro. Elimination of proliferating cells by exposure to high specific activity 3H thymidine at approximate intervals impaired the generation of cytotoxic activity. Elimination of cells proliferating to either syngeneic lymphoma or BN rat alloantigens allowed the remaining cells to generate cytotoxic potential to the second set of antigens. Elimination of proliferating cells also abrogated the ability of the in vitro generated cells to adoptively confer anti-tumor protection on nonimmune recipients. These results demonstrate that cellular division is required for the generation of cells which are cytotoxic in vitro and can adoptively confer anti-tumor protection in vivo.


The amino acid sequence of duck amyloid A (AA) protein.

AA protein constitutes 50 to 60% of the amyloid fibrils from livers of ducks developing spontaneous amyloidosis and has a m.w. of about 12,000. The sequence of the first 73 residues was established by automatic Edman degradation of the whole molecule and isolated cyanogen bromide fragments, and corroborated by placement of tryptic peptides. The sequence from position 76-80 was tentatively derived from a peptide that was homologous to that region of human and monkey AA proteins. Carboxypeptidase digestion showed the carboxy terminal sequence to be Ala, Arg, with some heterogeneity (Ser, Arg). Compared to human AA protein, there were five additional residues at the amino terminus. In view of the m.w. and the existence of additional peptides an extension at the C-terminal end seems likely. Sequence homologies to other AA proteins are discussed.


A neutrophil chemotactic factor and its inhibitor found in DNCB-induced skin inflammatory lesions.

Neutrophil chemotactic factor(s) and their inhibitors were explored in the acute inflammatory skin lesions induced by the application of 4% DNCB solution with acetone in guinea pigs. Skin biopsies were taken periodically and tissue extracts were made from the biopsy specimens. Neutrophil chemotactic activity found in such extracts reached a peak at 12 to 24 hr after the induction of the inflammation, when the lesions were found to be infiltrated predominantly with neutrophils. After 24 hr, the activity gradually diminished. Physicochemical and antigenic characterization studies on the chemotactic substance indicated that the material was most likely the cleavage product of C3. On the other hand, inhibitors against the neutrophil chemotactic factor were found in the tissue extracts which were obtained from the lesions at a later stage (48 to 96 hr after the induction of the inflammatory reaction). These inhibitors blocked not only the complement-derived chemotactic activity but also that obtained from bacterial culture filtrates. They were heat labile and showed striking heterogeneity in size on Sephadex gel filtration.


Histamine-induced inhibition of normal human basophil chemotaxis to C5a.

Histamine in concentrations as low as 10(-8) M inhibited the chemotactic response of normal human basophils to C5a. Histamine had no effect on basophil chemotaxis to lymphocyte-derived chemotactic factor. Histamine inhibition of basophil chemotaxis to C5a was prevented by metiamide, a drug which blocks H2 receptors for histamine. Since the accumulation of basophils in delayed cutaneous basophilic hypersensitivity (CBH) reactions may occur in part because of chemotaxis to C5a, and since C5a can induce histamine release, histamine inhibition of chemotaxis may limit basophil infiltration in CBH lesions.


Localization of receptors for activated complement on visceral epithelial cells of the human renal glomerulus.

Receptors for activated C3 have recently been demonstrated to be present in glomeruli of normal human kidneys. In the present communication, the precise location of these receptors within the renal corpuscle was studied with scanning electron microscopy. By this technique, the glomerular complement receptor (GCR) was found to be located on the visceral epithelial cell of the renal corpusle. This epithelial cell location was confirmed by comparison of in vitro GCR activity with the location of immunoglobulin and C3 deposited in vivo. Renal tissues in which Ig and C3 had been deposited in vivo diffusely in subepithelial loci had no in vitro GCR activity. Renal biopsies not showing Ig or C3 deposition or biopsies with Ig and C3 in the mesangium retained GCR activity. These results further confirm an important role for GCR in the trapping and deposition of C3 in some forms of immunologically mediated renal disease.


Resistance to murine leukemia in mice receiving simultaneous injections of syngeneic hybrid and parental neoplastic cells.

(A/J x C3H/HeJ)F1 mice (H-2a/k) exhibit no apparent resistance to the malignant proliferation of ASL-1 leukemia cells (H-2a), a spontaneously occurring neoplasm of A/J mouse origin. The period of survival after injections of ASL-1 cells is related to the number of cells introduced into the susceptible host. (A/J x C3H/HeJ)F1 mice receiving viable ASL-1 cells along with ASL-1 x LM(TK)- somatic hybrid cells (H-2a/k), syngeneic with the recipients, survived for statistically significant (p less than 0.001), longer periods than did mice receiving ASL-1 cells alone. Mice receiving ASL-1 and ASL-1 x LM(TK)- hybrid cells together survived for approximately twice as long as animals receiving ASL-1 cells alone. Mice receiving ASL-1 cells followed by hybrid cells survived for longer periods as well, but the therapeutic effects were less successful. ASL-1 x LM(TK)- hybrid cells are rejected after forming localized tumors by the immunocompetent F1 mice. In some instances, F1 animals previously rejecting hybrid cells and challenged subsequently with ASL-1 cells along with a second injection of hybrid cells survived indefinitely. The passive transfer of partial immunity to the leukemic cells could be achieved by injections of spleen cells from F1 mice that had rejected hybrid cells previously. Similar results were obtained for (A/J x C3H/HeJ)F1 mice receiving RADA-1 cells (H-2a), a radiation-induced leukemic line of A/J origin, along with RADA-1 x LM(TK)- hybrid cells (H-2a/k). The partial immunity induced by these lines of hybrid cells was cross-reactive: mice injected with ASL-1 cells and RADA-1 x LM(TK)- hybrid cells survived for prolonged periods, and vice versa.


Quantitation of immune complexes by competitive inhibition of binding of Clq to insoluble IgG aggregates.

An assay system for the binding of Clq to insoluble IgG aggregates was found useful for the quantitation of immune complexes in biological fluids. The assay, both easily and rapidly performed, is based on the competition of Clq binding substances with IgG aggregates. Serum from rheumatoid arthritis patients showed an increase in Clq binding substances over normal serum and this increase could be abolished by pretreatment of the serum with D-penicillamine.


Radioimmunoassay for anticollagen--antibodies using 14C-labelled collagen.

A sensitive radioimmunoassay for anticollagen antibodies is described. 14C-labelled human acid-soluble collagen of high specific activity (5 X 10(6) dpm/mg) is used as antigen either in native or denatured state. Experimentally induced anticollagen antibodies or RA synovial fluids containing antibodies to collagen are reacted with the labelled antigen. The immune complexes formed are precipitated with goat antiserum to rabbit globulins ('second antibody'). A systematic investigation of the labelled collagen in regard to cleavage by enzymes, fibril formation and specificity showed that no gross alteration had been caused by the labelling procedure. The assay furnishes information on the avidity, specificity and immunoglobulin class of experimental or pathological anticollagen antibodies. It can also be used as sensitive assay for collagen in biological fluids.


The estimation of lymphotoxic activity of ALS by spectrophotometric method.

Saijo's method of quantitation of the cytotoxicity of antiserum for tumor cells is adapted to estimation of lymphotoxic activity of antilymphocyte sera. The method is based on spectrophotometric measurement of an amount of trypan blue dye entering the lymphocytes damaged by action of ALS. Several possibilities of determination of the lymphotoxic titers of ALS are suggested.


Evaluation of the effect of ammonium chloride treatment on the activity of human effector cells in antibody-dependent and spontaneous cell-mediated cytotoxicity.

The effect of ammonium chloride treatment, used to eliminate contaminating red blood cells from lymphoid cell preparations, on the cytotoxic activity of human effector cells in antibody-dependent and spontaneous cell-mediated cytotoxicity was quantitatively determined. No significant difference between the cytotoxic efficiency of treated and untreated cell preparations was observed.


Immunoadsorbents for the isolation of high-affinity anti-hapten antibodies in high yield.

Anti-hapten antibodies with affinities close to 10(8)/M can be isolated in high yield by elution under mild conditions from immunoadsorbents prepared by coupling haptens directly to an aminoethylamino (AEA) derivative of beaded agarose. In experiments with rabbit anti-2,4-dinitrophenyl (DNP) antibody with an average association constant (Ko) of 1.2 X 10(9)/M, elution of antibody bound to a Sepharose-AEA-DNP column produced a yield of 57%. With rabbit antibody to the 5-dimethylaminonaphthalene-1-sulfonyl (DANS) hapten with Ko=2.7 X 10(8)/M and a Sips heterogeneity index a=0.52, a 20% yield of the antibody found in the starting material by quantitative precipitin analysis was obtained by specific precipitation and dissolution of the precipitate with 0.18 M Na DANSulfonate; this antibody had Ko=6.6 X 10(8)/M and a=0.66. Purification of another aliquot of the same antibody preparation by immunoadsorption on DANS-AEA-Sepharose and elution with the same hapten concentration produced a yield of 75% of antibody with Ko=5.7 X 10(7)/M and a=0.29. In 3 production runs with the new method, apparent yields of 181, 101 and 94% (based on quantitative precipitin analysis of the starting material) of anti-DANS antibody were obtained. In 2 of these runs, the immunoadsorbent was further eluted with 0.1 M acetic acid and then with 0.1 M acetic acid in 10% dioxane; additonal yields of 9 and 4% were obtained with acetic acid and further yields of 15 and 11% with acetic acid/dioxane; the antibody eluted with acetic acid was damaged as shown by its failure to mediate passive immune lysis of DANS-coupled sheep erythrocytes, but the antibody eluted with acetic acid/dioxane was recovered intact.


Improved efficiency of mouse, guinea pig and human C3b inactivator at low ionic strength, and reproducible immune-adherence with mouse complement.

Inactivation of homologous C3b by heated guinea pig, mouse and human serum was found to be much more rapid and complete at low ionic strength (0.037) than at micron = 0.15. The C3b inactivator in human and mouse serum was somewhat unstable to heating at 56 degrees C. Heated guinea pig serum showed the greatest ability to inactivate heterologous C3b, and human serum the least. Suramin (1 mg/ml) completely blocked homologous C3b inactivation by heated human, guinea pig and mouse serum, and 0.1 mg/ml was effective with mouse but not with human or guinea pig serum. Immune-adherence reactions with mouse C3 produced somewhat unstable hemagglutination patterns, which were improved by using ovalbumin in the buffer and minimizing EAC exposure to warm temperatures. A prozone phenomenon was frequently observed in immune-adherence hemagglutination with mouse C3, and less frequently with guinea pig and human C3.


Biometrical implications of factorial experiments for the study of lymphocyte mitogenic response.

Lymphocyte responsiveness to mitogens is affected by a number of experimental variables; the latter may be conveniently studied several at a time, following a factorial design that allows the complete evaluation of the effects of each variable and of their interplays. Statistical inferences may be drawn through an analysis of variance, provided that the data conform to the underlying model, i.e. that the effects are additive and that the errors are normally distributed and homoscedastic. Thymidine incorporation data should first be transformed to log cpm; the effects on the metameter may then be assumed to be additive, and their errors approach normality; the error variances may be affected by the experimental variables involved, so that the homogeneity of the error must be checked before relying on the pooled estimate of the error for parametric tests of significance. The above considerations have been illustrated with factorial experiments on [3H]TdR incorporation by rabbit spleen cells stimulated with varying amounts of PHA-P or PHA-M, under a variety of culture conditions.


The adjuvant activity of saponin and aluminium hydroxide for promoting reagins.

Saponin and aluminium hydroxide were compared as adjuvants for promoting serum reagins in cattle using BHK cell lysate as allergen and the passive cutaneous anaphylaxis test to demonstrate the antibodies. Saponin was the better adjuvant and provoked reagins in all the injected cattle while aluminium hydroxide did so in only 2 or 5 animals. The titres were also higher in the former case. A combination of both adjuvants stimulated reagin titres marginally higher than saponin alone while BHK cell lysate without adjuvant failed to provoke demonstrable reagins.


Chloasma, oral contraceptives, and plasma immunoreactive beta-melanocyte-stimulating hormone.

Plasma immunoreactive beta-melanocyte stimulating hormone (beta-MSH) has been measured in patients taking a progestogen-only oral contraceptive and in patients taking combined estrogen-progestogen therapy, of whom some had chloasma. Plasma levels did not differ significantly from those in a group of age- and sex-matched controls. It is concluded that the pigmentation of chloasma is not due to increased plasma concentrations of immunoreactive beta-MSH.


Hamster ear model for sebaceous glands.

The ventral side of the earlobes of Syrian hamsters richly endowed with sebaceous glands. These glands are large and are similar to human sebaceous follicles since they have an infundibulum, a sebaceous duct, multiple lobules, and a pilary unit which enters from below into the gland. In this study we have measured gland size by planimetry,and cellular activity by autoradiography using tritiated thymidine and tritated histidine. Males have much larger glands in sagittal sections than do females(0.1750 mm2 vs 0.0727 mm2, p less than 0.001) and a higher labeling index (19.85% vs 14.3%, p less than 0.01). Injection of testosterone propionate increases the gland size in female hamsters to 0.2362 mm2 (p less than 0.001). The labeling index also increases. The turnover of the total gland population is 12 to 14 days. Androgen sensitivity, gland size, and turnover time make the sebaceous glands on the ventral surface of the hamster earlobe a suitable model for study.


Sensitization potentials of methyl, ethyl, and n-butly methacrylates and mutual cross-sensitivity in guinea pigs.

Guinea pigs could be strongly sensitized to methyl, ethyl, and n-butyl methacrylates in ethanol or olive oil by the topical route, or in saline by the intradermal route. For elicitation of skin reactons, topical challenge with the compounds in olive oil or intradermal challenge with saline as the solvent was neccessary. Topical challenge with the methacrylates in ethanol failed to elicit any allergic skin reactions because of their volatility. All sensitized animals responded strongly not only to the inducing methacrylate but also to the other methacrylates, showing that mutual cross-sensitivity had occurred. Since methyl methacrylate has been reported to be a potent sensitizer in humans, the guinea-pig model described here may be useful for screening products before marketing.


Chronicled metastases in a hamster melanoma.

Fortner's Melanotic Melanoma No 1 was inoculated into the right hindfoot of 86 golden hamsters. Three, 7, 14, 21, and 28 days after inoculation, groups of hamsters underwent amputations at the ipsilateral hindhip to determine when pulmonary metastases initially occur. Upon subsequent sacrifice of the hamsters, pulmonary metastases were found to occur initially within 14 days of tumor inoculation.


Studies on 133Xe wash-out from human skin: quantitative measurements of blood flow in normal and corticosteroid-treated skin.

Blood flow was measured by the 133Xe technique in normal and corticosteroid-treated skin. Epicutaneous and intracutaneous methods of tracer application were compared in normal skin. The two labeling methods were equally suitable for measuring cutaneous blood flow provided calculations in both cases were based on a biexponential resolution of the wash-out curve in its cutaneous and subcutaneous components and provided the traumatic hyperemia phase was considered, when intracutaneous application of the tracer was used. Results were invalidated if calculations were based on initial slope of the wash-out curves.Topical application of beta-methasone valerate in a reduction in cutaneous blood flow as measured by the intracutaneous technique with curve resolution, whereas no effect could be demonstrated when calculations were based on the initial slopes of the curves. The 133Xe technique is a simple and reliable method for measuring cutaneous blood flow, which might prove useful in estimations of penetration ability and potency of topical corticosteroids.


The incorporation of tritiated uridine in hair germ and dermal papilla during dormancy (telogen) and activation (early anagen).

During dormancy there is very little incorporation of [3H]uridine in cells of hair germ and dermal papilla. During activation (both spontaneous and experimental) there is a marked increase in this parameter, expecially in the cells of the germ. After experimental activation by plucking, the increase in label in the germ is evident by 6 hr, reaching an initial maximum by 24 hr. The initial increase in [3H]uridine incorporation after activation precedes the increase in [3H]thymidine incorporation found previously, by about 6 hr. No evidence was found that the increase in [3H]uridine of papilla cells precedes the increase in [3H]uridine of germ cells. This finding militates against the possibility that the dermal papilla is triggered into an inductive role (vis-á-vis the germ cells) by means of circulating steroid hormones.


Cholestrol and cholesteryl ester content in normal and pathologic scale.

Using a sensitive new assay, we have measured the cholesteryl ester and cholesterol contents of stratum corneum from callus, normal skin, psoriatic lesions (plantar and nonplantar), and lamellar ichthyotic lesions (plantar and nonplantar). Cholesteryl ester content of normal stratum corneum was significantly higher than that of callus, suggesting that callus was not a suitable control tissue for further biochemical studies involving sterol content of stratum corneum. Both psoriatic and lamellar ichthyotic scale have increased levels of free cholesterol and decreased levels of esterified cholesterol when compared to appropriate controls.


Characterization and hormonal control of the androgen receptor in the hamster sebaceous glands.

The costovertebral organs [CVO] and seminel vesicles [SV] of the hamster exhibit high saturable androgen uptake. The physicochemcal characteristics of the cytoplasmic androgen receptor present in these tissues have been determined and compared to those obtained in rat prostate[P]. Using the synthetic androgen R 1881 [methyltrienolone] as a radioactive ligand, it has been shown that the affinity of this compound for the cytosol CVO receptor [Kd = 0.7 +/- 0.1 nM] is similar to that for the crytosol SV receptor [Kd = 2.4 +/- 0.9 nm] in hamsters and the cytosol P receptor [Kd = 0.6 +/- 0.1 nM] in rats. The hormonal specificity of binding in these tissues is restricted to androgens. Moreover, testosterone and dihydrotestosterone have the same relative binding affinity in CVO and SV compared to R 1881. Following castration, the total number of androgen sites, as measured by an exchange assay with R 1881, decreases rapidly and parallels with a fall in lipogenic activity. Administration of an androgen rapidly restores binding capacity.


Long-term sweat collection using salt-impregnated pads.

To facilitate a study of the pharmacokinetics of drugs dissolved in sweat, a technique was devised for collecting sweat at a steady rate over an 8-day period. Three normal subjects each wore 4 absorbent pads applied to their skin under waterproof dressings for 8 days. The absorbent pads were either plain cotton or cotton impregnated with sodium chloride crystals. Each pad (3 cm x 3 cm) was applied to an area of skin (2 cm x 2 cm) defined by an adhesive template, and was removed daily, weighed, and replaced, to determine progressive uptake of sweat. Sweat uptake by plain cotton pads reached a plateau value within 2 to 3 days and did not significantly increase thereafter; in contrast, uptake by the salt-impregnated pads continued at a steady rate for the full 8 days of the study (mean rate 0.79 mg/cm2/hr, SD = 0.16, N = 6). This effect may be related to an osmotic gradient across the skin, but the physiologic mechanisms are not completely clear. This appears to be a convenient tool for the collection of sweat over long periods at a steady rate.


Kinetic characterization of hemostasis in thermal injury.

Hemostasis has been characterized by kinetic measurements in 12 patients with severe burns. Survival and turnover of 51Cr-platelets, 131I-fibrinogen, and 125I-plasminogen were simultaneously measured in 10 patients within 24 hours of injury; the disappearance times were shortened in concert to approximately 20% of normal values, and platelet and fibrinogen turnover were increased to more than three times normal. Serial studies in five of these patients 3 and 5 weeks later showed progressive improvement in kinetic measurements ,but normal values were not achieved. Two additional patients with similar rates of consumption demonstrated localization of radiolabeled platelets and fibrinogen in the burn wound. Heparin therapy did not modify consumption significantly. Enhanced fibrinolysis was reflected by marked reduction in 125I-plasminogen survival, depletion of the plasma plasminogen levels, and elevated levels of fibrin degradation products. Initial low levels of platelets and fibrinogen were followed by compensatory elevations; factor V and prothrombin complex factors were depressed during the first five days, but factor VIII levels were not reduced. Thermal injury is characterized by marked and prolonged consumption within the wound of platelets, fibrinogen, and plasminogen that is not reversible by heparin. This process depletes hemostatic components and causes bleeding when the burn is massive or complications are severe.


The role of heparin on platelet retention by acrylonitrile co-polymer dialysis membranes.

The role of heparin on platelet--foreign surface interactions was examined by platelet retention studies on acrylonitrile--dimethylaminoethyl methacrylate (AN-DMAEMA) dialysis membranes both with and without the bonding of heparin onto their surfaces. Heparin bonding significantly reduced platelet retention. Heparin in solution (4 units/ml.) increased platelet retention when the surface of the membranes was modified by ethylene oxide but had no significant effect on the platelet-retaining properties of unmodified membranes. Studies using heparin 99mTc demonstrated that unmodified membranes took up heparin from solution whereas ethylene oxide-modified membranes had little such affinity. The heparin bonding process greatly increased the heparin uptake achieved by simple soaking in heparin solution, and the leaching rate was less than 1% at 70 hours. The results indicate that heparin has two antagonistic effects in this platelet-foreign surface interaction: it acts directly on platelets to increase adhesiveness while acting on the foreign surface to reduce platelet retention.


False elevation of plasma cortisol in congenital adrenal hyperplasia.

Plasma cortisol values in seven patients with the 21-hydroxylase variant of CAH ranged from 9 to 35 micron/100 ml. (mean+/-S.E.=22+/-4) as determined fluorimetrically and from 22 to 35 microng/100 ml. (26+/-2) by competitive protein-binding radioassay. In these same patients the cortisol values obtained after Sephadex LH-20 column chromatography were much lower, ranging from 1 to 12.5 microng/100 ml. (5+/-2, p less than 0.01). In six normal subjects, cortisol values were similar before and after chromatography. Plasma concentrations of progesterone, 17alpha-hydroxyprogesterone, and 21-deoxycortisol in the CAH patients were increased 10 to 100-fold. The elevated cortisol values determined by customary methods were shown to be due to cross-interference of these and other steroids in the assays. Plasma cortisol values obtained routinely are falsely elevated and therefore misleading as a gauge of adrenal insufficiency in CAH.


Fibrin formation and dissolution in women receiving oral contraceptive drugs.

Factors affecting fibrin formation and dissolution were compared for 15 women taking combined oral contraceptives and 15 women using nonpharmacological methods of birth control. The two groups were matched for age, body weight, time of blood collection, and day in menstrual cycle; none of the women was receiving other drugs known to affect the blood coagulation or fibrinolytic parameters measured in this study. Fibrinogen concentrations tended to be higher in the experimental group; the degree of fibrinogen degradation, number of fibrin cross-links, and levels of factor XIII and plasminogen were the same for both group. There were significant reductions in antithrombin activity, the euglobulin lysis time, and fibrinolytic inhibitor level in women using oral contraceptives. An estrogen dose effect was suggested for fibrinogen concentration and the degree of antithrombin activity. The increased fibrinolytic activity and decreased fibrinolytic inhibitor levels are consistent with in vitro observations that antithrombin also inhibits plasmin activity. Thus while oral contraceptive-induced depression of antithrombin III could possibly predispose to thrombosis by diminishing the inhibition of the serine protease clotting factors, the concomitant decreased level of plasmin inhibition might balance the system by favoring thrombolysis as well as the digestion and inactivation of certain clotting factors by plasmin.


Studies in neuronal ceroid-lipofuscinosis: leukocyte peroxidase deficiency in a patient with neuronal ceroid-lipofuscinosis (Jansky-Bielschowsky type).

Leukocyte peroxidase deficiency has been demonstrated in a confirmed case of neuronal ceroid-lipofuscinosis with guaiacol, o-dianisidine, and p-phenylenediamine used as hydrogen donors in the peroxidase assay system. Nitroblue tetrazolium (NBT) reduction values in the leukocytes of the patient were also found to be significantly higher than those of normal controls, indicating the impaired hydrogen peroxide catabolism. When the patient was given a daily dose of vitamin E (400 I.U.), vitamin C (1 gm), and methionine (1 gm.) along with a weekly intramuscular injection of vitamin B12, the leukocyte peroxidase values of the patient returned to normal levels in about 7 weeks. NBT reductions values also decreased to normal levels. The regenerated enzyme in the patient's leukocytes was shown to have similar chromatographic and electrophoretic properties as the leukocyte peroxidase of normal controls. After about 28 weeks of therapy, the peroxidase levels in the leukocytes of the patient returned to original low levels, with concomitant increase in the NBT reduction values. The effect of vitamin therapy on normal control subjects was, at least in some cases, an increase of leukocyte peroxidase. A significant increase in the peroxidase levels of the patient's leukocytes during vitamin therapy remains unexplained, and the possibility of peroxidase deficiency being a secondary manifestation rather than the primary defect in Batten's disease cannot be ruled out.


The effect of bone matrix on young connective tissue cells in culture.

Human and rat decalcified bone matrix preparations were shown to be active in inducing cartilage formation by subcutaneous implantation in the rat. When young rat fibroblastic cells were grown in cultures, which also contained bone matrix preprations in particulate form, the fibroblastic cells underwent a uniform and consistent morphological alteration. These altered cells showed higher rates of synthesis of hyaluronic acid and chondroitin sulfate than the controls and exhibited very active amino-sugar-nucleotide metabolism. It is suggested that this approach to the culture of connective tissue cells will allow a more precise definition of the early steps of connective tissue differentiation.


Trauma as a stimulus to marrow regeneration in the osteosclerotic mouse.

Hemopoietic regeneration was studied in the tibia of mice rendered osteosclerotic by estrone injections. Trauma induced by fracture and periosteal damage was followed by a local hemopoietic response in both normal and osteosclerotic mice. Endosteal damage induced by drilling an artificial cavity in the osteosclerotic tibia was not followed by local hemopoietic regeneration, whereas in normal tibias similarly treated incomplete hemopoietic regeneration was observed. These studies indicate that trauma induced by fracture and periosteal damage is followed by a fairly uniform local hemopoietic regenerative response regardless of whether or not marrow is present in the traumatized bone. Creation of a simulated marrow cavity by drilling through osteosclerotic bone is an insufficient stimulus for hemopoietic regeneration in the mouse. New bone tissue was found to occupy the drilled shaft. This suggests that failure to regenerate hemopoietic tissue may be a consequence of insufficient bone resorption. A differential effect of trauma on endosteal and periosteal tissue is therefore postulated.


Evidence that decreased cardiac output is not the stimulus to sodium retention during acute constriction of the vena cava.

It has been proposed that the antinatriuresis during constriction of the TVC is due to a decrease in CO. We have compared the effect on sodium excretion of comparable reductions in CO by three separate methods: TVC constriction, PA occlusion, and LV infarction. Dogs were studied during 10% of body weight saline loading and again after TVC constriction, PA occlusion, or LV infarction. CO fell 26 to 31% in all groups; sodium excretion was not significantly altered after PA occlusion (474 to 533 micronEq/min.) or LV infarction (587 to 609 micronEq/min.) but fell significantly after TVC constriction (504 to 271 micronEq/min.). Renal and systemic hemodynamoderate reduction of CO per se does not cause sodium retention. PA and TVC dogs had comparable increments in vena caval pressure but opposite changes in RVEDP; 4 to 0.9 mm. Hg (TVC) and 0.5 to 9.1 mm. Hg (PA).


14C cyanate as a tag for red cell survival in normal and uremic man.

14C cyanate was employed as a red cell tag. Incubated cells were washed before reinjection to remove free cyanate. Neither early or late elution was observed, and the mean red cell life span of 10 normal subjects was 115+/-12 days. In nine uremic subjects the mean life span corrected for blood loss was 73 days with a mean red cell turnover of about 0.79 times basal. Survival curves in normal subjects were similar to those observed with DF32P and in uremic subjects to those with 51Cr corrected for elution. These observatios show the reliability of 14C cyanate as a nonelutable red cell tag.


Comparison of iodine monochloride and modified chloramine-T radioiodination for in vivo protein studies.

Aggregate formation on gel chromatography and shortened in vivo t1/2 have been shown to result from the usual chloramine-T (CT) radioiodination of proteins. A modified CT method with decreased CT: protein ratio has ben advocated, particularly for use in the 125I-fibrinogen uptake test. In the present study, such modified CT procedures with 131I were assessed by simultaneous injection in rabbits of iodine-125 monochloride protein standards along with the 131I-CT proteins. Standard clearance analyses were performed. For both albumin and fibrinogen a much reduced CT:protein ratio was required before satisfactory in vivo proteins were obtained. The ratio differed for the two proteins, with fibrinogen being more susceptible to CT-induced aggregate formation. Intermediate CT:protein ratios resulted in denaturation of only a portion of the labeled proteins as manifested by a low C1 with a normal t1/2 for the slow component. At intermediate ratios, unaggregated protein displayed abnormal clearance kinetics, indicating that denaturation was not solely the result of aggregates. The results indicated modified CT radioiodination can be used for in vivo studies, but only if carefully compared in vivo with more generally used radiolabeling procedures.


Breakdown products of C3 and factor B in hemolytic-uremic syndrome.

Serum concentrations of Clq, C4, C3, and Factor B but not properdin were significantly decreased in patients with HUS compared to values in normal control subjects (p value less than 0.01). Sera from 13 HUS patients obtained early after the onset of the disease showed breakdown products of Factor B (Ba, Bb) by immunoelectrophoresis; 12 of these sera showed C3 breakdown products (C3c, C3d). Sera from seven patients studied 1 month to 3 years later no longer demonstrated any breakdown products of Factor B or C3. These data suggest that the complemented system is activate in HUS. The concept that immunological mechanisms play a major role in this disease is additionally supported by the occurrence of IgM, C3, and fibrin in glomeruli and renal vessels.


Detection of cytotoxic antibody to erythroblasts.

A two-stage test of cytotoxicity for erythroblasts has been developed that is faster and more sensitive than a previous method. Release of 59Fe from erythroid precursors was used as an index of cytotoxic injury. Optimal release was obtained by pretreating the labeled marrow cells with 0.46M reduced glutathione (GSH) at pH 8.0 for 1 hour at 37 degrees C. The first-stage test plasmas or IgG globulins were incubated with the treated cells at 22 degrees C. for 1 hour and the second-stage source of complement was incubated with the cells for 1 hour at 37 degrees C. These changes permitted cytotoxic plasmas to be detected when they previously would not have been identified. Substitution of the GSH by trypsin or neuraminidase did not yield comparable results. Measurement of the cytotoxicity for GSH-treated cells by the trypan blue exclusion technique showed that the loss of exclusion of trypan blue by marrow erythroblasts increased with an increased release of 50Fe. No cytotoxicity was detected if complement was inactivated at 56 degrees C. The results observed with trypan blue and the occurence of cytotoxicity with the addition of IgG globulins and complement indicate that this system can be used to detect cytotoxic antibody to erythroblasts.


Effects of sulfinpyrazone on platelet prostaglandin synthesis and platelet release of serotonin.

Sulfinpyrazone added to PRP inhibited the release of serotonin induced by collagen. The inhibitory effect depended strongly on the strength of the collagen stimulus. Serotonin release was also inhibited (up to 73%) in PRP prepared from subjects who had ingested the drug. This is the first demonstration of a direct effect of a sulfinpyrazone in vivo on in vitro tests of platelet function. Prostaglandin synthesis was studied with lysates of washed platelets, arachidonic acid-14C, and silicic acid chromatography to isolate a reaction product which was tentatively identified as thromboxane B2. Platelet prostaglandin synthesis was shown to be strongly inhibited by sulfinpyrazone. Inhibition was competitive with respect to substrate. It is proposed that effects of sulfinpyrazone on platelet function may be due to inhibition of prostaglandin synthesis. The competitive nature of sulfinpyrazone inhibition may explain why sulfinpyrazone is a strong inhibitor of the release reaction under conditions of dilute collagent stimulation but is weak in the presence of stronger stimuli. In comparing the potency of inhibitors of platelet prostaglandin synthesis the nature of inhibition must be considered. Competitive inhibitors may be incorrectly regarded as weak if studied only at high substrate concentration.


A simple screening test for arginase deficiency (hyperargininemia).

A simple fluorescent spot screening test has been developed for the identification of individuals with arginase deficiency (hyperargininemia). The assay is based on the coversion of arginine to ornithine and urea by arginase present in 1/8 inch disc of dried blood on filter paper. The enzyme activity is visually estimated by the oxidation of NAD-H to NAD+ in a coupled kinetic reaction. In the absence of the enzyme, there is no oxidation of the NAD-H and consequently no loss of fluorescence. The screening assay has been used to identify successfully both heterozygous and homozygous arginase-deficient crabeater macaques (M. fascicularis) as well as three patients with hyperargininemia. This test can be used to screen large numbers of patients with mental retardation or seizure disorders rapidly to determine the frequency of this disorder more precisely.


Quantitative determination of erythrocyte zinc protoporphyrin.

An elevated zinc protoporphyrin (ZPP) level in blood is indicative of lead poisoning (as well as iron-deficiency anemia) and is the basis for certain fluorometric screening tests. The calibration of such test protocols and instruments requires ways to reliably determine absolute ZPP concentrations in blood. Two such methods are described: one is an ethanol extraction method and the other a fluorometric addition method using detergent hemolyzed blood. A careful determination of the molar extinction coefficient of ZPP gives EmM=161 in pyridine. Corrections are offered for a previously published protocol for determining the ZPP concentration from the fluorescence intensity of diluted blood. The choice of units for expressing the ZPP concentration in blood is discussed, as is the absorbance correction in quantitative fluorometry of samples which are not optically thin at the excitation wavelength.


Estimation of the state of saturation of brushite and calcium oxalate in urine: a comparison of three methods.

The estimation of the degree of saturation of brushite and of calcium oxalate in urine of patients with disorders of calcium metabolism has been proved to be an effective tool in evaluating the patient's propensity to form renal stones. The methods used in three different laboratories have been compared and evaluated in 27 urine samples. Relative saturation ratio (ratio of activity product and thermodynamic solubility product of brushite) and activity product ratio (ratio of activity product of original sample and that obtained after incubation of sample with synthetic brushite) were determined. Similar studies were performed for calcium oxalate. The values for relative saturation ratio of brushite or calcium oxalate differed widely among the three techniques. However, nearly identical values for activity product ratio of brushite were obtained. The activity product ratios of calcium oxalate, obtained by different techniques, closely approximated each other except in sampels containing excessive amounts of calcium (greater than 5 mM) or oxalate (greater than 5 mM). The values for the relative saturation ratios for both brushite and calcium oxalate were usually higher than the corresponding values for activity product ratio. The results indicate that the use of activity product ratio provides a more simple and reliable estimate of the urinary state of saturation than does the relative saturation ratio.


Radioiodinated derivatives for steroid radioimmunoassay. Application to the radioimmunoassay of cortisol.

Gamma-emitting steroid tracers for use in the radioimmunoassay of steroids have a number of advantages over the more common tritiated tracers. The steroid derivatives aldosterone3-(p-hydroxybenzoyl) hydrazone, aldosterone-3-(p-hydroxyphenylpropionyl)hydrazone, deoxycorticosterone-3-(p-hydroxyphenylpropionyl)hydrazone, and cortisol-3-(p-hydroxyphenylpropionyl)hydrazone were synthesized by a one-step procedure and iodinated ([125I]). To illustrate the usefulness of these derivatives, we describe the details of a cortisol radioimmunoassay. The use of the radioiodinated tracer appeared to increase the specificity of the antigen-antibody reaction when compared with [3H]cortisol. The methodology involved in the preparation of the steroid derivatives described above can be extended to other 3-oxo-4-ene-containing steroids, with the advantages of economy, simplicity, and versatility.


Subcellular distributions of lipids in cultured BHK cells: evidence for the enrichment of lysobisphosphatidic acid and neutral lipids in lysosomes.

Homogenates of cultured hamster fibroblasts (BHK 21 cells) were fractionated by differential centrifugation into six main fractions: nuclear, mitochondrial, light mitochondrial, microsomal, soluble, and floating. The contents of several lipids and some marker enzymes were measured. According to the enzyme distributions, lysosomes were enriched both in the floating fraction and in the light mitochondrial fraction. Lysobisphosphatidic acid was enriched in the floating fraction more than tenfold relative to phospholipid. Cholesteryl esters and triglycerides were the main constituents of the fraction (70% of total lipids). Lysobisphosphatidic acid, triglycerides, and cholesteryl esters were enriched also in the light mitochondrial fraction. Their distribution patterns were different from those of the other lipids. Electron microscopy showed that the floating fraction contained numerous lipofuscin-like particles with darkly stained peripheries and with core regions staining like droplets of neutral lipids. Similar particles, frequently containing prominent multilamellar formations, were also common in intact cells. They contained cytochemically identified acid phosphatase. We conclude that lysobisphosphatidic acid was enriched in the lysosomes of the BHK cells and that the lysosomes also contained variable amounts of neutral lipids in the form of intralysosomal droplets.


Effect of an aqueous phase on the solubility of cholesterol in an oil phase.

In the absence of water, the solubility of cholesterol in triolein at 21 degrees C was 2.8%. When water was added to the system, the solubility of cholesterol in the oil phase decreased to 1.9%, and cholesterol monohydrate precipitated. The precipitation of the sterol evidently resulted from the excess concentration of the surface-active cholesterol at the interface, allowing the rapid interaction of water with cholesterol and the resulting formation of cholesterol monohydrate with its attendant lower energy and less soluble crystalline lattice. The ternary phase diagram for the system cholesterol--triolein--water, modified to include cholesterol monohydrate formation with the consequent decrease in sterol solubility; differs from the previously reported phase diagram. Other cholesterol--oil--aqueous systems related to biologically important lipids were studied. Cholesteryl oleate was more soluble than cholesterol in triolein (23% at 21 degrees C), and this value did not decrease when water was present. Water caused cholesterol to precipitate from cholesteryl linoleate at 37 degrees C. Thus crystalline cholesterol may be present in lipids found in atherosclerotic plaques at a lower concentration of free cholesterol than had been predicted previously. In another experiment, a micellar taurocholate solution precipitated cholesterol from triolein and from corn oil. These effects of aqueous systems suggest the possibility of cholesterol precipitation from dietary fat when it becomes mixed with water in the diet or stomach, or with the micellar phase in the intestine. Plant sterols were precipitated also from oil solutions by an aqueous phase. Water-induced sterol precipitation is a phenomenon that could occur in a variety of biological systems, and may be applicable to sterols in general.


Sterol metabolism studies in the rat. Effects of primary bile acids (sodium taurochenodeoxycholate and sodium taurocholate) on sterol metabolism.

Sterol metabolism studies using a combination of isotopic and chromatographic procedures were carried out in rats fed either a low-cholesterol stock diet or a stock diet containing 0.1% cholesterol. The primary bile acids, sodium taurochenodeoxycholate and sodium taurocholate, were added to the stock diets at a level of 0.5%, as required. Feeding sodium taurochenodeoxycholate and sodium taurocholate led to a decrease in acidic steroid synthesis, cholesterol turnover, and cholesterol balance, compared to controls. Sodium taurochenodeoxycholate feeding did not influence cholesterol absorption, but rats fed sodium taurocholate showed a twofold increase in cholesterol absorption as well as an accumulation of cholesterol in the liver. Rats receiving diets containing sodium taurochenodeoxycholate or sodium taurocholate plus cholesterol (0.1%) showed decreased acidic steroid synthesis, cholesterol turnover, and cholesterol balance, compared to the corresponding controls (Group 2, high cholesterol diet). Significantly larger amounts of cholesterol were absorbed in the taurocholate group (34.1 mg/day); these animals increased their concentrations of cholesterol in liver and plasma. The rats fed taurocholate plus 0.1% cholesterol differed from those fed taurochenodeoxycholate plus 0.1% cholesterol in the following respects: a) increased cholesterol absorption (35%), and b) accumulation of cholesterol in liver and plasma.


Bile acid synthesis in man. II. Determination of 7 alpha-hydroxycholesterol, (22R)-22-hydroxycholesterol, and 26-hydroxycholesterol in human meconium.

7 alpha-Hydroxycholesterol, (22R)-22-hydroxycholesterol and 26-hydroxycholesterol have been quantitated in human meconium. The method used tetrahydrofuran for extraction and solvolysis of the sulfate esters, liquid partition chromatography for the separation of the hydroxysterols, gas-liquid chromatography for quantitation, gas-liquid chromatography-mass spectrometry for identification, and tritiated and 14C-labeled tracers for overall recovery standards. (22R)-22-Hydroxycholesterol and 26-hydroxycholesterol were present almost entirely, ( greater than 93%) in the sulfate fraction at concentrations of 3.8-6.4 and 0.4-0.8 mg per 100 g meconium, respectively. Since free tritiated (22R)-22-hydroxycholesterol was used as the tracer to assess recovery of this hydroxysterol, the concentrations found for this compound may be minimal. Tritiated 26-hydroxycholesterol 3,26-disulfate was used as tracer to determine the levels of this compound, and the solvolysis procedure was optimized for recovery of 26-hydroxycholesterol and least decomposition of 7 alpha-hydroxycholesterol. No significant amounts of 7 alpha-hydroxycholesterol were found based on the tracer-free hydroxysterol as recovery standard.


Stimulation by serum of 32P incorporation into the phospholipids of Ehrlich ascites cells.

Ehrlich ascites cells adapted for suspension culture were incubated with 32PO43- in a Krebs-Ringer-HEPES (N-2-hydroxyethyl-piperazine-N'-2-ethanesulfonate) buffer with or without 5% calf serum. Specific activity was determined for cellular [gamma-32P]ATP, total phospholipids, and the individual phospholipids fractionated by two-dimensional thin-layer chromatography. Serum stimulated the incorporation of 32P into the phosphatides with a 2-3-fold increase in specific activity of phosphatidylcholine and phosphatidylethanolamine. Phosphatidylinositol showed a moderate increase. Phosphatidic acid showed an increase that could be accounted for by a parallel small increase in the specific activity of precursor [gamma-32P]-ATP. The effect os serum could be discerned as early as 10 min after its addition. Complete inhibition of protein synthesis by cycloheximide or puromycin did not interfere with the serum stimulation of 32P incorporation into lipids, indicating that the serum effect is not dependent on synthesis of new protein. Incubation with palmitic acid caused a marked increase of phosphatidylinositol specific activity, little change in specific activity of phosphatidic acid but a tripling of its total amount, and no changes in the other phosphatides. Oleic acid caused only a small increase in phosphatidylinositol specific activity and no significant changes in the other lipids.


Lipid metabolism in regressing rat corpora lutea of pregnancy.

Lipid accumulation is a hallmark of corpus luteum regression and we characterized lipids stored in rat corpora lutea of pregnancy between days 21 and 24 post coitum, the period of luteolysis. A 10-fold rise in lutein triglyceride concentrations occurred between days 21 and 24, which represented the major alteration in luteal lipid metabolism during luteolysis, coinciding with the appearance of numerous lipid droplets in the luteal cells. The fatty acid composition of luteal triglycerides was altered between days 20 and 23 in a pattern consistent with the influx of blood triglyceride fatty acids. No evidence for increased de novo fatty acid synthesis by luteal tissue between days 21 and 24 post coitum was obtained using in vitro methods. [14C]Acetate incorporation into lipids declined between days 16 and 24 and label was preferentially introduced into long chain polyunsaturated fatty acids. Rates of tritium incorporation into fatty acids from tritiated water were relatively low. [14C]Glucose was predominantly incorporated into the glycerol moiety of luteal lipids and incorporation of label into this fraction was augmented between days 21 and 23 post coitum. The incorporation of [14C]palmitate into triglycerides of luteal tissue during in vitro incubation also increased between days 21 and 23. In vitro lactate production, [14C]glucose oxidation, and [14C-palmitate oxidation to 14CO2 increased significantly during this time. We conclude that specific biochemical alterations occur in regressing corpora facilitating uptake and storage of blood glyceride fatty acids as triglycerides. The physiological significance of this triglyceride accumulation remains to be elucidated.


Determination of cholesterol absorption in man by intestinal perfusion.

In this study a technique is described for estimating net absorption of total cholesterol (endogenous + exogenous) that enters the intestine. The method employs intubation of patients with a 3-lumen tube that contains a 10-cm mixing segment in the duodenum and a 100-cm absorption segment in the jejunum. A liquid formula diet containing varying amounts of exogenous cholesterol is infused continuously into the upper duodenum for a period of several hours; the formula diet stimulates constant contraction of the gallbladder and thus provides for continous secretion of biliary cholesterol sitosterol as a marker, the input of endogenous + exogenous cholesterol can be measured at the end of the 10-cm mixing segment. Net cholesterol absorption is estimated from the disappearance of cholesterol relative to beta-sitosterol over the next 100-cm of jejunum. When radioactive cholesterol was also used as a marker, radioactivity usually disappeared more rapidly than the mass of choleesterol over the absorption segment; this suggests that a significant amount of isotope exchange occurs in the upper intestine. Using beta-sitosterol as a marker, the extent of exchange can be determined. In six patients, cholesterol inputs ranged from 51 to 118 mg/hr, and net percentage absorption was 34-56%. When inputs of cholesterol were acutely increased by enhancing exogenous cholesterol, absolute absorption was uniformly increased, but percentage absorption either remained the same or was decreased somewhat. Changine inputs of beta-sitosterol had a striking effect on cholesterol absorption, and relatively small increments of beta-sitosterol almost always produced corresponding reductions in uptake of cholesterol. The intestinal perfusion method appears to provide certain advantages over previous techniques for estimating total cholesterol entering the upper intestine, including that derived from both endogenous and exogenous sources. Measurements can be made over short periods of time, and the  method allows for determination of effects of acute changes in the intestinal milieu on cholesterol absorption. Finally, the technique defines the extent of isotope exchange between cholesterol in the intestinal mucosa and in the lumen.


Effect of the rate of oxygen consumption on muscle respiration.

An important role of myoglobin in red muscle is to facilitate the diffusion of oxygen for metabolism. We consider a model for muscle respiration in which the oxygen consumption is of a Michaelis-Menten form. The resulting mathematical model is solved in two different ways with two different boundary conditions. The first uses the singular perturbation method of Murray (1974), while the second, which gives another justication of the simpler procedure, is a direct numerical computation of the full problem. The oxygen tension and saturation are often small. For realistic values of the Michaelis-MENTEN CONSTANT the oxygen tension, the saturation and the radius of the region in which the oxygen tension is negligibly small can be calculated using the constant consumption model of Murray (1974), with corrected boundary conditions (those for a Stefan problem), which in certain circumstances mardedly affect the solution.


A bifurcation analysis of pattern formation in a diffusion governed morphogenetic field.

We discuss from an analytical point of view the mechanism of pre-pattern formation in a diffusion governed morphogenetic field. The model here considered is a normalized form of one of the models, proposed by Gierer and Meinhardt, based on the general principle of lateral inhibition. The results, obtained in the framework of bifurcation theory, shows that there is a spontaneous formation of a gradient both for activator and inhibitor concentrations if the ratio between the mean squares of the diffusion ranges of inhibitor and activator is greater than a well defined critical value.


A model for macromolecular selection in complementary instructing systems.

In this paper we consider a model for the selection and evolution of biological macromolecules when their reproduction is based on complementary instruction. The model is an extension of one of Eigen's models for selection and takes in account explicitly the formation of both single stranded and double stranded molecular complexes. We construct exact solutions to the rate equations for the case of constant rate parameters and error distributions. Criteria for selection are discussed.


Pattern prediction for moving cells.

A continuous-time Markov chain model consisting of four positional and directional states is used to predict the eventual relative positioning of two motile cell types. It is assumed that the period of observation is small in comparison with the generation time of both cell types. The method is useful in predicting developmental phenomena and is applicable to complex patterns involving more than two types of cells.


Some population genetic models combining artificial and natural selection pressures in the presence of assortative mating.

We have attempted quantitatively through a series of assortative mating models to gain insight into the interaction between the usually antagonistic tendencies of artifical and natural selection pressures. We summarize some of the robust conclusions. In cases where natural selection is expressed only through the phenotype and acts in the opposite direction to the culling incline, then fixation of the dominant or recessive type can be achieved and which occurs depends critically on the initial composition of the population and the magnitude of the degree of culling compared to the selection coefficients. With traits determined at two loci in the case that the double heterozygote is the desired kind, the effect of selfing can only be overcome by very strong artificial selection pressures (high culling order). The degree of culling to achieve its objective can be relaxed with weakening of linkage. The relevant comparison is r2+(1-r)2less than 2(1-c) indicating the precise extent of culling needed, to prevent fixation. The relationships are more complex when natural selection forces are also involved (see Model IV).


On periodic solutions of a delay integral equation modelling epidemics.

A delay-integral equation, proposed by Cooke and Kaplan in [1] as a model of epidemics, is studied. The focus of this work is on the qualitative behavor of solutions as a certain parameter is allowed to vary. It is shown that if a certain threshold is not exceeded then solutions tend to zero exponentially while if this threshold is exceeded, periodic solutions exist. Many features or the numerical studies in [1] are explained.


Processing visual signals with nonlinear spatial filters.

The properties of nonlinear spatial filters as a major part of the peripheral nervous system are investigated with respect to processing of two types of signals: a deterministic stepfunction and Graussian noise. The nonlinearity of the nerve cell is treated as a threshold element. It is shown that certain unfavorable characteristics of linear filters do not occur in such nonlinear filters. The basic nonlinear effects of combined space-time-filtering are demonstrated by using bandpass filters. Time-and space-dependent noise is applied to the nonlinear bandpass. The two subsystems formed by linear bandpass section and the threshold are treated separately. Two examples for the application of nonlinear spatial filtering are given.


Ovarian venous blood flow in non-pregnant and pregnant rats.

A modified venous outflow technique was used to measure ovarian blood flow in the rat. The rate of flow through the right ovary was 0-198+/-0-009 (S.E.M.), 0-476+/-0-076 and 0-958+/-0-162 ml/min in six Day 0 (dioestrous), five Day 16 and six Day 22 pregnant rats respectively. The intravenous administration of 50 i.u. human chorionic gonadotrophin increased ovarian blood flow by 26+/-4, 57+/-19 and 46+/-9% respectively, from 2 to 8 min after the injection. The present ovarian venous outflow results are substantially higher than those previously reported in the rat but agree with values determined with radioactive microspheres.


Sexual behaviour of neonatally castrated rats injected during infancy with oestrogen and dihydrotestosterone.

Male rats were castrated on the day of birth (day 1) and injected with either testosterone, dihydrotestosterone, a synthetic oestrogen (RU 2858 + dihydrotestosterone, or oil from days 1 to 5. The aromatizable androgen, testosterone, and RU 2858 suppressed both cyclic gonadotrophin secretion, indicated by the absence of corpora lutea from implanted ovarian grafts, and the behavioural response to oestradiol benzoate + progesterone injections in adulthood. The 5alpha-reduced androgen, dihydrotestosterone alone did not affect gonadotrophin secretion or female receptive behaviour, but like testosterone, it increased penis development in response to testosterone propionate, and this was positively correlated with copulatory efficiency, i.e. the ratio of intromission to mount frequencies. Nevertheless, ejaculation only occurred among animals that had received testosterone or RU 2858 + dihydrotestosterone. The results support the concept that during the preinatal period, neural conversion of androgens to oestrogens is important both for the suppression of female gonadotrophin secretion and behaviour patterns as well as for the organization of male behaviour patterns. The 5alpha-reduction of unsaturated C19-steriods to dihydrotestosterone in peripheral tissues is also required to complete the development of the male genital tract.


Protein biosynthesis in vitro by the pars intermedia of the mouse pituitary gland.

During short-term incubations of isolated posterior pituitary glands of the mouse, isotopically labelled amino acids were incorporated into protein by the cells of the pars intermedia. Using labelled leucine, 5-10% of incorporated label was found in a protein (P1) with a molecular weight of about 75 000. Protein P1 could be isoalted from both fresh and incubated tissue, and was a normal and indeed major, secretory product of the ppars intermedia. constituting more than 50% of the protein present.


Decidualization and ovum-implantation in spayed mice treated with oestriol.

Single injections of oestriol were partially effective in sensitizing the uterus to a decidual stimulus and inducing ovum-implantation in progesterone-treated spayed mice, whereas two injections (6 h apart) were fully effective. It seems that in the progestational uterus, as in the non-progestational organ, oestriol can induce a full oestrogenic response provided that its level in the target organ is maintained. It is also concluded that ovum-implantation is not triggered by some transient early effect of oestrogen, but requires about 12 h of sustained oestrogen action for its successful completion.


Morphine tolerance acquisition as an associative process.

The results of several experiments supported the proposal that morphine analgesic tolerance is a manifestation of an association between the drug administration ritual and the systemic effects of the drug: (a) Presenting environmental cues previously associated with morphine, but without the drug, attenuated established tolerance (i.e., morphine tolerance can be extinguished), (b) repeated presentations of the morphine administration procedure, prior to its pairing with the opiate, retarded the acquisition of tolerance (i.e., morphine tolerance is subject to "latent inhibition"), and (c) placebo sessions interspersed between morphine sessions deleteriously affected the development of tolerance (i.e., morphine tolerance is subject to the decremental effects of partial reinforcement). These findings appear inexplicable by most traditional theories of tolerance, which do not emphasize the role of drug-associated environmental cues in the development of tolerance. Additionally, it is suggested that the conditioning analysis of tolerance is congenial with a current view of habituation, and there may be a similar associative basis for the response decrement to both endogenous and exogenous iterative stimulation.


Pairing novel exteroceptive cues and illness reduces illness-induced taste aversions.

Four experiments are reported that lead to the conclusion that pairing novel exteroceptive stimulation (placement into a black compartment) with a poison (lithium chloride) attenuates the development of an aversion to a taste (saccharin) subsequently paired with the poison. Such an attenuation effect occurs whether the exteroceptive cues are present or absent when the taste-poison pairing is administered. Interpretation and implications of this finding are discussed.


Disruption of a taste familiarity effect by novel exteroceptive stimulation.

Preexposed or familiar tastes are normally retarded relative to novel tastes in acquiring aversive properties as a consequence of being paired with an illness-inducing event. Four experiments are reported which demonstrate that such a taste familiarity effect can be significantly disrupted by exposing the animal to novel exteroceptive stimulation just prior to conditioning with the familiar taste. Implications of this finding for theories of taste aversion learning are discussed, and two potential theoretical accounts of the data are suggested.


Selective suppression of drinking during a limited period following aversive drug treatment in rats.

Administration of lithium chloride disrupted the intake of flavored solutions but not water in rats. This intake suppression was directly related to the amount of lithium administered (Experiment 1), occurred with both palatable and unpalatable novel saccharin solutions (Experiment 2), but was only observed if subjects were tested starting less than 75 min. after lithium treatment (Experiment 3). Twenty-five daily exposures to saccharin did not attenuate the effect (Experiment 4). However, in saccharin-reared and vinegar-reared rats, lithium did not disrupt consumption of the solutions these subjects had access to throughout life, even though suppressions of intake were observed when these subjects were tested with novel flavors (Experiment 5). The selective disruption of drinking is interpreted as a novelty-dependent sensitization reaction to the discomfort of aversive drug administration.


Conditioned stimulus as a determinant of the form of the Pavlovian conditioned response.

The role of the conditioned stimulus (CS) as a determinant of the form of the Pavlovian conditioned response (CR) was investigated in five experiments. Both stabilimeter measures of general activity and detailed observations of the behavior of the rat subjects in the presence of CSs anticipatory to a food unconditioned stimulus (US) were obtained. In Experiment 1, substantially different behaviors to light and tone CSs were observed; further, these differences were found to be dependent on specific learning experience rather than on the mere presence of different stimulation at the time of response evocation. Experiments 2 and 3 investigated the possibility that there was considerable communality of learning to light and tone CSs despite their evoking different CRs. In Experiment 2, prior conditioning of either the tone or light CS was found to block the acquisition of various behaviors to the added element when a light-tone compound stimulus was reinforced, even though the pretrained stimulus did not itself evoke those behaviors. In Experiment 3, the nature of second-order conditioned responding was found to be similar regardless of which first-order CS was used as the reinforcer. Additionally, the reinforcing powers of the light and tone CSs were found to summate. Experiments 4 and 5 examined behaviors to a variety of visual and auditory stimuli paired with food. Stimulus modality and the localizability and vertical location of visual stimuli were found to influence conditioned responding. These results suggested that in this conditioning situation, similar learning of a CS-US relation may be displayed in different overt CRs, depending on the nature of the CS.


Effects of bilirubin on red cell metabolism.

Blirubin causes certain defects in erythrocyte metabolism, mainly in glycolysis. These effects of bilirubin were studied in vitro using a relatively physiological assay medium, which consisted of heparinized whole blood. Bilirubin was added in a small quantity of NaOH solution. In the presence of bilirubin a reduced glucose consumption of red cells and an accelerated depletion in the ATP and glycerate-2,3-bisphosphate concentration was found. Bilirubin levels lower than 50 mumol/l did not influence the glucose consumption. In agreement to other investigations it was established that bilirubin causes haemolysis of red cells. ATP-deficient cells are more sensitive to this effect.


[Determination of the urinary metabolites hydroxyindole-acetic acid, vanillyl mandelic acid and homovanillic acid by means of lipophilic gel chromatography and gas chromatography (author's transl)].

A specific and practicable method is described for the quantitative determination of urinary phenol- and indole-carboxylic acids. High specificity is achieved by a preliminary separation of the free acids (extracted from the urine sample) with the aid of organophilic gel chromatography on Sephadex LH 20, followed by gas chromatographic analysis of the silyl derivatives of the acids. The organophilic gel chromatography of the free acids shows a high recovery rate in the micro- and submicrogram range. The difficulties encountered in other techniques in the derivatisation and gas chromatographic separation of the individual components are avoided by using the preliminary separation, and by using N-methyl-N-trimethylsilyl-trifluoroacetamide for the derivatisation. Use of this preparation technique with a direct read-out gas chromatograph with automatic sample introduction, gives high accuracy and precision, and a facility for the determination of a wide range of aromatic acids in urine.


[Comparison of amino acids in human serum and plasma (author's transl)].

Using standardized analytical methods amino acids in human serum and plasma were compared. Identical concentrations of the studied amino acids are found in serum and plasma, which are prepared immediately after blood sampling. If protein precipitation is performed after storage of the serum sample at 4 degrees C or 22 degrees C for 10 or 24 hours, concentrations of some amino acids are significantly changed.


Recognition of random shapes followed at varying delays by attended or unattended shapes, digits, and line grids.

Three experiments evaluated the effect of poststimulus distractor characteristics in altering recognition of random shapes. Experiment 1 demonstrated that when 150 msec or 300 msec were allowed for processing the initial shape stimulus, recognition was lowered only when it was followed by an attended shape or digit distractor. Unattended shapes, digits, and line grids and attended line grids left recognition essentially perfect. Attended shapes lowered recognition more than attended digits. Experiment 2 found that attended shapes, digits, and line grids all masked random shapes when presented immediately upon offset of a random shape displayed for 50 msec. As processing time increased, digit distractors became less effective than shape distractors, while line grids lost all effect. The shape distractors lowered recognition up to 1,200 msec. Experiment 3 showed that the larger recognition loss produced by the shape distractor than by the digit distractor could not be attributed to differences in response procedure. It was suggested that memory for random shapes moves from brief visual storage to a limited capacity visual short-term memory. Attended shape distractors may eliminate the stimulus shape from visual short-term memory thus preventing long-term storage.


Acquisition and retention of verbal associations to olfactory and abstract visual stimuli of varying similarity.

The similarity among a set of stimuli used in a paired-associate (PA) task was controlled by psychological scaling. Three lists of odorants and two lists of abstract figures (forms) with six stimuli in each list were constructed to have varying degrees of intralist similarity. Independent groups learned to associate digit responses with one stimulus list in a PA training session. Recognition of training stimuli presented among 12 distractor stimuli and recall of the associations was tested after 7 days. Within each modality, increased intralist similarity impaired PA acquisition. Between modalities, acquisition was inferior with the odor stimuli. During recognition testing, the olfactory modality supported inferior performance. In recall testing, equivalently learned responses in the two modalities were equally well retained. There appears to be a perceptual limitation in olfaction relative to vision that influences stimulus encoding and stimulus retrieval processes but that does not affect retrieval of associated responses.


Associations to odors: interference, mnemonics, and verbal labeling.

In a paired-associate paradigm using odors as stimuli and pictures for multiple-choice responses, the first of two associations to an odor was retained far better than the second over a 2-week period. The persistence of first-learned associations may be responsible for the long lasting nature of odor memories. Subjects reported constructing mediational schemes for mnemonic devices to link the odors and pictures. Latencies for a task of naming odors indicated that although naming odors is difficult, labels could be generated sufficiently fast that they could be employed as mediators in the paired-associate task. A third task investigated the phenomenon of knowing that an odor was familiar but being unable to name it. Subjects in this tip-of-the-nose state were questioned about the odor quality and the name of the odor and were given hints about the name. These subjects were found to have information available about the odor quality but none for the name as found in the tip-of-the-tongue state. However, as in the tip-of-the-tongue phenomenon, hints given to the subjects in the tip-of-the-nose state often led to the correct name.


Recognition memory for single tones with and without context.

Sequences of seven tones were presented, and recognition memory for individual tones of each sequence was tested under varying degrees of context. With no context, the test required recognition of a tone isolated from the sequence; with full context, the tone to be recognized was embedded in the original sequence. A series of three experiments demonstrated that recognition memory was far more accurate under full-context conditions than under no-context conditions and that the superiority was not wholly attributable to the serial position information or the order information provided by the full context. It is suggested that in addition to the processing of limited information for the pitch of isolated tones, pattern (or relational) information is abstracted from a tone sequence and is retrieved in the presence of full context.


Contextual influences on judgments of linear extent.

A series of experiments was performed to test the predictions of adaptation level, efferent readiness, and framing explanations of illusions of extent. The framing notion, that the ratio of total figure length to shaft length (i.e., the framing ratio) determines the magnitude of illusions, was supported for the Müller-Lyer, Baldwin, and divided line illusions. Peak overestimation of shaft length obtained when the framing ratio was 3:2. Variation of proximal figure size, achieved by altering either viewing distance or distal figure size, was found to be directly related to the magnitude of the illusions. A model was proposed to account for the effects of both the framing ratio and proximal shaft length on judgments of focal length.


Comparative judgment: tests of two theories using the Baldwin figure.

Two theories of comparative judgment were compared across four experiments on their ability to explain the Baldwin figure, a focal line whose apparent length is affected by square boxes at or near its endpoints. Left-box size, right-box size, line length, line-box distance, and other variables were varied in factorial designs to allow application of functional measurement methodology. The model from adaptation level theory did poorly in several respects. In particular, it had trouble with the pervasive lack of contrast. Further, it could not account for the fact that a box added contralaterally increased the illusion, whereas the same box added ipsilaterally decreased the illusion. The model from information integration theory did substantially better, though it too had trouble with some of the results. An alternative interpretation was suggested in which the Baldwin figure is viewed as a positive context or assimilation effect. This positive context formulation may generalize to other illusions, such as those produced by the Müller-Lyer and Ponzo figures.


Perceptual load in searching for sloping colored lines camouflaged by colored backgrounds: a separate-groups investigation.

Altogether 168 men searched briefly for colored sloping lines embedded in a background of random color. Using a separate-groups experimental design, search for six kinds of target was found to be less effective after practice than search for a single kind of target. Reducing the number of colors of targets from three to one was considerably more beneficial than reducing the number of main directions of slope from two to one. Reducing the number of kinds of target without reducing the number of relevant stimulus values was also found to improve the effectiveness of search, but search was even more effective when the number of relevant stimulus colors was reduced. The results can be predicted from the total number of selection operations required. However, a more precise fit needs to reflect the considerably greater difficulty of searching for a number of directions of slope. When targets were poorly camouflaged, search was equally effective whether there were four colors or only a single color of target to search for.


Dynamic properties of radial and tangential movements as determinants of the haptic horizontal--vertical illusion with an L figure.

In four experiments involving blindfolded subjects, constant errors in the haptic judgment of extent in the horizontal plane were found to relate consistently to the time and velocity of limb movement. Radial movements, executed at a slower speed and for a longer time, are judged longer than tangential movements of equal extent. The data were considered in relation to certain physiological and kinematic properties of the actively moving limb. Taken together with additional information on judgments of movement duration, the results suggest that the illusion of extent is modulated by the perception of differential time cues. In these terms, it was noted that the haptic horizontal-vertical illusion with the L figure is another instance of the interaction of apparent space and time commonly found in studies of psychological relativity.


Ear differences in evaluating emotional tones of voice and verbal content.

Two experiments are presented in which lateralization of monaural, auditory input affected the evaluation of verbal passages. In Experiment 1, subjects listened to taped passages that consisted of three levels (positive, neutral, and negative) of tone of voice crossed with three similar levels of content or meaning, making a total of nine different tone/content combinations. Subjects rated these passages as positive, neutral, or negative, and although they were not instructed about which cues (tone or content) to use, 29 of 36 subjects who listened on the left ear primarily used the tone-of-voice cues to rate the passages, whereas 21 of 36 subjects who listened on the right ear used the content cues (p less than .01). In Experiment 2, subjects were asked to make objective ratings of both tone of voice and content. Subjects who listened on the right ear were more accurate in rating both cues. The lateral differences in evaluating the auditory stimuli are discussed in the framework of the left hemisphere's specialization for analytic processing of objective information and the right hemisphere's specialization for the holistic processing of subjective or emotional information. However, each hemisphere's specialization for tone and content cues can be greatly affected by the demands of the experimental task.


Sequential effects in judgments of loudness.

A multiple regression analysis of sequential effects in magnitude estimation and absolute identification is presented as an alternative to the approach used by Lockhead and his students. The new analysis indicates that sequential effects do not extend over more than one trial. This is in agreement with the response ratio hypothesis. A more detailed multiple regression analysis of these sequential effects indicates that the magnitude of the correlation between successive responses is heavily dependent on the decibel difference between successive signals. This is not in agreement with the response ratio hypothesis, and the hypothesis is reformulated to take account of this finding. This modification of the model is tested by comparing distributions of normalized responses to theoretical distributions suggested by the model and to a possible alternative distribution.


The symptom of chest pain in family practice.

A chart review study was conducted on 109 family practice patients with the complaint of chest pain. Overall and age-sex specific rates were established for chest pain of organic and of unproven etiology. Fifty percent of the chest pain was of unproven etiology after six months follow-up. The highest incidence rate of chest pain was in middle-aged males; they also had the highest incidence of chest pain of unproven etiology. For females, the highest rate of chest pain of unproven etiology was also in the 45 to 64-year age group. The greatest male-female differences for chest pain of unproven etiology were seen in the 15 to 24-year (female predominance) and the 25 to 44-year (male predominance) age groups. Patients with chest pain of unproven etiology had a significantly greater incidence of anxiety-depression than a control group (matched for age, sex, and practice) and a group of organic chest pain patients. Characteristics of the chest pain were also examined, but there were few differences in the description of the chest pain between the patients with chest pain of organic and unproven etiologies.


Benign hereditary nephritis.

The diagnosis, prognosis, and heredity of glomerulonephritis, in 207 members of one family over five generations was determined. No evidence of significant renal insufficiency or renal associated mortality was found. A history of urinary tract infections was obtained from 58 percent of those with hematuria. Several of those with nephritis also had high-frequency hearing losses. Two females with histories of urinary infections had elevated levels of serum creatinine. Many cases will probably be discovered if families are tested when a patient presents with benign recurrent hematuria with or without red blood cell casts. There may not be an obvious history of kidney disease or hematuria. Hereditary nephritis is not always a progressive renal disease.


Genetic aspects of manic-depressive disease in family practice.

Bipolar affective disorder (manic-depressive disease) is a mental disturbance characterized by phases of both depression and mania. Mania is essential to the diagnosis and is characterized by elevated mood, flight of ideas, and increased psychomotor activity. Current psychiatric literature not only shows that this disease is familial but has also demonstrated, through linkage studies, that an X-linked dominant mode of inheritance adequately explains the strong prevalence of bipolar affective disorder in some families. The family discussed here shows many of the known clinical aspects of bipolar affective disorder. It serves as an example consistent with the X-linked dominant mode of inheritance. Knowledge of the genetic background of this disease aids the family physician by helping to identify members of the family likely to have acquired this condition. The family physician can then look for future problems in them and in their offspring, leading to earlier diagnosis and more effective management. Thus, a member of a  bipolar family with supposed unipolar illness (depression only) might be better served with the prophylactic use of lithium carbonate because of his likelihood of possessing a bipolar genotype. The prophylactic use of this drug has been shown effective in reducing the frequency, duration, and intensity of both manic and depressive mood swings.


Evaluation and management of suicidal behavior.

The danger of suicide is highest in depressed older people, especially men who have sustained a loss, who have an attitude of hopelessness, and who have not resolved feelings of grief. Factors associated with greater risk are chronic or serious illness, divorced, separated or widowed marital status, white race, drug abuse, excessive use of alcohol, unemployment, and poor living conditions. Commonly, those who commit suicide have made previous attempts and have directly or indirectly communicated their intention to others. The family physician is in the front line in the recognition and prevention of suicide. In the treatment of the suicidal, the physician should maintain a strong positive relationship to the patient and be consistently dedicated to his care including availability to see the patient frequently and to receive phone calls in the middle of the night. Those with the most serious risk should be referred to a psychiatrist and hospitalized to protect them from their suicidal impulses. Psychotherapy, antidepressant and tranquilizer drugs, and electric shcok treatment are the main therapeutic approaches. The physician's capacity for empathy and emotional commitment is of greater importance than his professional credentials.


Practical aspects of prescribing drugs for ambulatory patients.

One of the largest areas of concern in ambulatory medicine is the treatment of patients with drugs. This is of importance in short-term, acute processes and is especially vital in treating long-term, chronic problems. There are three primary areas of concern in treating ambulatory patients: dosage forms, compliance to the prescribed regimen, and the multiplicity of drugs. This paper discusses the proper use of the various dosage forms available: liquid, tablets, suppositories, and ointments. The physician should be knowledgeable about the drugs he uses and should take a rational approach to the selection and prescription of drugs in everyday practice.


Strategy for defining the clinical content of family medicine.

The clinical content of family medicine is yet to be defined and arranged into a structured system of knowledge. To provide this systematic approach, it is suggested that a set of problem "profiles" could be identified as basic to family medicine, and binary decision and problem-solving chains identified for each. In addition, each problem profile might be expected to provide a consistent "masquerading" format for specific unusual problems. Certain "red flags" would be expected to be relevant to specific uncommon problems of medicine. A method of identifying these "masquerades" and "red flags" is proposed.


Effective use of patient resources: a training guide for family physicians.

Effective use of resources available to patients in their homes, in their neighborhoods, and in their communities can give the family physician much assistance in the provision of total health care to his patients and their families. Patients' resources can be divided into two broad categories--"Personal" and "Institutional". Examples of the former are family, church, neighbors, unions, etc. Institutional resources can be public or private, and they cover a broad spectrum of services. Patients' needs for dignity and independence are best served by Personal resources. Institutional resources should be used only for those services that cannot be met any other way. Success in using any resource requires an orderly five-step process which is presented and discussed in this paper.


Behavioral science in family practice: an ethical imperative.

Behavioral science confronts at least three major problems within American medicine that must be overcome if the family physician of the future is to receive an adequate graduate education and maintain his professional integrity. Through increasing specialization, the once unified biological perspective of man was severely fragmented, and with increasing emphasis on the science of medicine, the disease process was objectified and reified. Twentieth century man joined his myth of technological mastery with medicine's desire to eliminate pain and suffering. This gave rise to the idea that life could be medically managed and existential dilemmas anesthetized. To overcome these problems behavioral science has two ethical issues to address in family medicine. First, behavioral science must restore the physician's sense of personhood by recognizing the person of the physician as the primary diagnostic and therapeutic "tool" of family practice. Second, behavioral science must help family practice refocus its professional responsibility on the social problems of the day. This will happen through a critical review of the custodial aspects of the physician's role and an emphasis on role innovation. Approaches to these two ethical issues at the Medical University of South Carolina family practice residency are described.


The Teacher Interest Profile Registry of AAFP: implementation and effectiveness.

In order to assist in the recruitment of physicians from practice into teaching during a period of rapid expansion in family practice education in the United States, the Division of Education of the American Academy of Family Physicians developed a computerized listing of members of the Academy who were interested in being contacted about available faculty positions. This computerized list, containing pertinent information about the professional qualifications of the registrants, became known as the Teacher Interest Profile Registry and was made available upon request to recruiting program administrators in 1974-1975. An evaluation of the utilization and effectiveness of the registry was conducted by staff of the Division of Education in the spring of 1975 by means of mailed questionnaries to the two groups utilizing the service: program administrators and physician-registrants. Results of these surveys revealed that one out of every eight programs using the registry was successful in recruiting one or more new faculty members, with a total of 27 new faculty reported as having been recruited through the use of this service. In view of the relative  success of this program in identifying potential faculty members and the continued interest and utilization of the service, academy leaders have decided to continue this service until it is no longer effective and/or needed.


Use of video tape in teaching psychological medicine.

Video tapes have been used extensively in medical education and especially in training for family practice. This article describes the use of video-tape equipment in rural health centers at the Rockford School of Medicine, University of Illinois, College of Medicine. The video camera was incorporated into clinical transaction by having it operated by a psychiatrist-preceptor in the presence of the patient. This method makes available an intimate glimpse of the clinical situation, less disturbed by intrusive gadetry than has heretofore been possible. Patients seem mostly unaffected by the taping, so long as clinical personnal sanction it, and the function is firmly placed within the supportive bounds of the doctor-patient relationship.


The CR Alpha Diagnostic Coding System for ambulatory care.

A three-digit code system for patient encounters in ambulatory care was constructed to meet the criteria of integrity, retrievability, flexibility, and acceptability. The system is distinguished from other comparable codes by the use of an alphabetical letter as a category designator, the provision of "open" areas within each category for the addition of new rubrics in appropriate sequence, and the availability of "open" categories for use in research or expansion. The system has the capacity to expand from 22 primary categories to 97 subheadings and to a maximum of 3,200 rubrics. The system uses both diagnostic and symptom-oriented rubrics. The diagnostic terms are adopted from the International Classification of Diseases, Adapted, Eighth Revision (ICDA-8) and the symptoms from the National Ambulatory Medical Care Survey Symptom Classification.