Preparation and subfractionation of isologous and heterologous anti-idiotypes, using FV fragments. Fv fragments prepared from the BALB/c anti-dinitrophenyl (DNP) myeloma proteins, produced by plasmacytoma MOPC 315 and XRPC 25, were used to raise anti-idiotypic antibodies in rabbits. Anti-idiotypes to these proteins were also prepared in the syngeneic BALB/c mice by injecting the intact proteins, whereas Fv fragment failed to induce antibodies in these mice. Rabbit anti-Fv of late bleedings did not show the presence of antibodies to "framework determinants" (determinants common to all V regions of mouse immunoglobulins), and they contained precipitating anti-idiotypes whereas mouse antisera contained non-precipitating anti-idiotypes. No cross-reaction was observed between anti-idiotypes to these myeloma proteins and induced anti-DNP antibodies from BALB/c mice, when either rabbit or mouse antisera were analyzed. The anti-sera were fractionated into anti-binding site and anti-non-binding site by adsorption onto the immunogen-Sepharose column and elution by DNP lysine, followed by elution with acetic acid. Only the anti-binding sites were inhibited by hapten in their interaction with the homologous myeloma protein. The rabbit anti-Fv antibodies were predominantly (over 90%) anti-non-binding site whereas the mouse anti-idiotypes were predominantly (60 to 70%) anti-binding site.


Two types of antibody dependent cell-mediated cytotoxicity, arming and sensitization. Haptenated chicken erythrocytes, anti-hapten antibodies and normal spleen cells were used for a sutdy of parameters of antibody-dependent cell-mediated cytotoxicity (ADCC). Anti-hapten antibody was introduced to the reaction either bound to the target cells (sensitization) or to the effector cells (arming). Our data suggest that the same effector cells and the same antibodies were responsible for both types of reactions. More antibody was required for arming (ca. 1 ng/ml) than for sensitization (ca. 10 pg/ml). Antibodies of several mammalian species could cooperate in ADCC with human, rat, or guinea pig spleen effector cells, but fowl antibodies were inefficient in the arming of mammalian effector cells. Rat and human spleen cells were powerful effector cells whereas guinea pig, rabbit, and mouse spleens yielded weakly cytotoxic suspensions. Rabbit antibodies, on the other hand, were efficient, but rat antibodies were less efficient in ADCC. Mouse and guinea pig antibodies appear to take an intermediate position. Our data suggest that ADCC effector cells of the spleen contain phagocytic and nonphagocytic cells, and the non-phagocytic effector cells still constitute a heterogenous population.


In vitro synthesis of immunoglobulin and anti-viral antibody in Aleutian disease viral infection of mink. Lymphoid cells from Aleutian disease virus (ADV)-infected and noninfected mink were cultured in vitro and the synthesis of Ig M, IgG, and viral-specific antibody measured. Compared to noninfected mink, lymph node cells from mink with Aleutian disease (AD) contained a higher percentage of plasma cells and immunoglobulin-bearing lymphocytes, synthesized significantly more IgG, and produced detectable quantities of ADV-specific antibody. No significant difference in IgM synthesis was observed.


Possible evidence for antibody-dependent macrophage-mediated cytotoxicity directed against murine adenocarcinoma cells in vivo. A macrophage-mediated antibody-dependent cellular cytotoxic reaction has been described in a syngeneic murine mammary adenocarcinoma model. The antibody appears to be present in two forms, one apparently complexed with antigen and the other identified as 7S immunoglobulin on Sephadex G-200 and as the IgG2a subclass by blocking of Fc receptors on the macrophages. This antibody is first detected in mice with regressing tumors. Tumor cells from immune mice appear to be coated with this antibody, as they are sensitive to the effects of normal macrophages in vitro, whereas tumor cells from immunologically compromised mice are not. Thus, a macrophage-dependent reaction probably is relevant in the in situ immune defenses against this tumor.


Idiotype of inulin-binding antibodies and myeloma proteins controlled by genes linked to the allotype locus of the mouse. The serum from non-immunized mice of strains BALB/c, C58, A/He, and RIII contained hemagglutinins for stearoyl inulin-coated SRBC. Immunization with bacterial levan slightly elevated these titers. These same sera also carried cross-specific idiotypic determinants (IdX) that are associated only with inulin-binding myeloma proteins (INBMP) of BLAB/c mice. Three InuldX specificities, A, B, and G, were identified. The InuIdX phenotypes of strains BALB/c, C58, and A/He were InuIdXA+B+G+; strain RIII was InuIdX A+B-G+; strain C57BL/6, C57BL/10, DBA/2, AKR and NH were A-B-G-. Strains CBA, C3H, PL, and C57L could not be typed because of low and inconsistent levels of InuIdX and anti-inulin hemagglutinins. The InuIdXA+B+G+ phenotype was used as a genetic marker in immunoglobulin congenic strains CB-20, BAB-14, and BC-8 and in Bailey RI strains which are derived from crosses of BALB/c (InuIdXA+B+G+) and C57BL/ka or C57BL/6, respectively (InuldXA-B-G-). Linkage of the IdXA+B+G+ to the BALB/c a allotype locus was demonstrated. In addition, the InuldXA+B+G+ marker was used as a phenotype in an analysis of 168 first generation backcorss progeny (C57BL X (C57BL X BALB/c) F). Linkage of the marker to the BALB/c allotype was found again. Two proven recombinant mice having the C57BL a allotype and the InuIdxA+B+G+ markers were identified and progeny tested. Four other potential crossover types are still being progeny-tested.


Modification of H-2 antigenic sites by enzymatic treatment influences virus-specific target cell lysis. Vaccinia virus-infected cells were treated enzymatically to remove H-2 antigenic sites. The effect of this procedure on virus-specific cell-mediated cytolysis (CMC) and virus-specific antibody-mediated cytolysis (AMC) was tested. Due to the inhibition of cellular proteinsynthesis by the vaccinia virus infection, H-2 antigenic sites were not resynthesized while there was a continuous production of viral surface antigens. These cells with a high concentration of viral surface antigens and decreased H-2 determinants could be used as targets in the virus specific AMC which emphasizes the significance of H-2 antigens during recognition of virus-specific determinants by T cells.


Functional characterization of rat mast cell arylsulfatase activity. Extracts of isolated rat peritoneal mast cells were demonstrated to contain appreciable quantities of arysulfatase activity. The enzyme was inhibited by both phosphate and sulfate ions and demonstrated a pH optimum of 5.0. The enzyme was recovered in the eluate of DE-52 columns and appeared to have a m.w. of 150,000 of Sephadex G-200 gel filtration. These findings and the anomalous kinetic behavior of the enzyme suggest that at least part of the enzymatic activity is of the arylsulfatase IIA type. While spontaneous release of the enzyme was observed, challenge of isolated rat mast cells with a goat anti-rat IgE serum resulted in a significant increase in release of the enzyme. The arylsulfatase activity extracted from isolated rat mast cells demonstrated comparable activity in inactivating slow reacting substance of anaphylaxis (SRS-A) to that described for human eosinophil and lung arylsulfatase.


Disc-crossed immunoelectrophoresis. A simple "laying-on" technique permitting the use of commercially available agarose. A technique, disc-crossed immunoelectrophoresis, is described to provide a simple and convenient means of performing electrophoresis in polyacrylamide gel in a discontinuous buffer system (disc electrophoresis) followed by electrophoresis into antibody-containing agarose gel. A simple washing of the polyacrylamide gel in distilled water combined with a "laying-on" method, seems to be a satisfactory and rapid way to obtain immunoprecipitation patterns of high quality using commercially available agarose in the second electrophoresis.


Separation of lymphocyte sub-populations using antibodies attached to staphylococcal protein A-coated surfaces. Plastic surfaces which had been coated sucessively with IgG, Staphylococal protein A (SpA) and diluted whole antiserum specific for cell membrane antigens, were used successfully to separate rabbit lymphocyte sub-populations. This method does not require the purification of SpA or antibody, and uses only small quantities of antiserum. The specificity of the cell separation method was demonstrated using various rabbit "b" locus anti-allotype sera, and the number of cells removed by the SpA-antiallotype system correlated well with the number of Ig+ve or "B" lymphocytes detected by other methods. Optimal conditions for cell attachment could readily be determined using multi-well plastic trays, and the adherent cells rapidly quantitated. Using 125I-labelled rabbit IgG (Rb IgG) or sheep IgG (Sh IgG) it was possible to quantitate the amount of IgG coupled to plastic surfaces, or binding to SpA-coated surfaces. By using 125I-labelled (As4) Rb IgG it was also possible to estimate the amount of antibody bound to SpA. The wide application of the SpA-antibody method relative to other affinity-antibody methods is discussed.


Short-term microcultures of lymphocytes from Chinese hamster peripheral blood. A microtechnique for the culture of Chinese Hamster lymphocytes is described using Cooke microtiter plates with 100,000 leucocytes in a culture volume of 0.1 ml and a culture time of three days. The culture media used were RPMI 1640 and Trowell T8 supplemented with 20% foetal calf serum (FCS) and 2 mu PHA. The cells were harvested with a Skatron cell culture harvester using glass fibre filters. Various technical aspects of the lymphocyte cultures from the Chinese Hamster are described. The relevance of changes in culture conditions to the variability of culture results was analysed for PHA and FCS concentrations, different culture media, cell concentration, vessel shape and culture duration.


Bacteriology of the lower respiratory tract as determined by fiber-optic bronchoscopy and transtracheal aspiration. For assessment of the validity of cultures of tracheobronchial secretions and exudates (TBSE) obtained by fiber-optic bronchoscopy, the aerobic and anaerobic flora of expectorated saliva and TBSE obtained by fiber-optic bronchoscopy from nine healthy volunteers and eight patients were compared with those obtained by fiber-optic bronchoscopy as well). Normal volunteers yielded both aerobic and anaerobic bacteria in amounts usually less than 104.5 colony-forming units (cfu)/ml in TBSE obtained by fiberoptic bronchoscopy. In patients with chronic bronchitis, 42 isolates of aerobic bacteria (104-105.5 cfu/ml) and only 10 isolates of anaerobes (usually less than 104 cfu/ml) were reovered from 15 samples obtained by trantracheal aspiration. The data lead to the conclusion that low-level contamination (less than or equal to 104 cfu/ml) with oral flora is common in TBSE obtained by fiber-optic bronchoscopy. A single potential pathogen in numbers of greater than or equal to 105 cfu/ml may be of etiologic significance, particularly if recovered from purulent drainage material from a localized portion of the lung. Under circumstances in which quantitative bacteriology cannot be done, TBSE obtained by transtracheal aspiration will most reliably reflect the bacterial flora present in the lung.


Endemic dengue virus infection in Hispaniola. I. Haiti. Antibodies to group B arbovirus were common among coastal populations in the Haitian part of the Caribbean island of Hispaniola. Antibodies were present in 43% of children one to five years old; prevalence in older persons increased with age. In nine asymptomatic persons serodiagnostic changes indicative of group B arbovirus were detected during six of twelve consecutive months. In port cities where antibodies were common in children, Aedes aegypti indices of 50%-70% were observed; in contrast, no A. aegypti mosquitoes were found in an inland village in which children lacked denjue hemagglutination-inhibiting antibodes. Between 1969 and 1971, dengue 2 virus was isolated from 11 persons with episodic febrile illnesses, although no epidemic was apparent. These findings indicate that dengue virus infection was endemic in Haiti during the period of the study.


Lack of leukocyte migration inhibition by hepatitis B antigen and normal nonspecific immunoreactivity in asymptomatic carriers. The immune response to hepatitis B surface antigen (HBS Ag) was studied in 25 asymptomatic carriers by the leukocyte migration-inhibition (LMI) test in agarose. In the presence of purified HBS Ag, inhibition was demonstrated in only four of 25 carriers, in contrast to 24 of 28 patients who cleared the antigen after acute infection with hepatitis B. Tuberculin purified protein derivative (PPD) was also used as an antigen for the LMI test in these carriers. Inhibition was demonstrated in only 12 of 25 individuals who had positive PPD skin tests, in contrast to all of 14 normal noncarrier individuals with positive PPD skin tests and none of 12 normal noncarrier of the asymptomatic carriers gave normal results. The lack of an immune response to HBS Ag was thought to be responsible for the persistence of the antigen and also for the absence of symptoms.


Amikacin in treatment of infections caused by gram-negative bacteria resistant to gentamicin and other aminoglycosides: clinical and bacteriologic results. Amikacin (250 or 500 mg) was administered intramuscularly twice daily at 12-hr intervals to 34 patients with infections due to various gram-negative bacteria. Usually one or more aggravating factors were present, such as serious underlying pathology or therapy with steroids or immunosuppressants. Clinical isolates from most patients were resistant to gentamicin and other aminoglycosides. The overall response to therapy was excellent in 20 patients; in eight patients clinical response was good, but the organism persisted. Six patients showed some improvement without complete resolution of the infection or eradication of the causative organism. There were no complete clinical or bacteriologic failures. Ototoxicity was not observed in any patient. Levels of blood urea nitrogen and serum creatinine increased in two patients but returned to pretreatment levels within two weeks after therapy. No other adverse reactions were noted. Amikacin may replace gentamicin as initial therapy in serious gram-negative bacillary infections, particularly when resistance to gentamicin is a problem.


Clinical pharmacology of amikacin and kanamycin. During and after a 4-hr intravenous infusion of amikacin and kanamycin in a cross-over study in healthy adult male volunteers, average concentrations of drug in serum were similar, with half-lives of approximately 2 hr. Apparent volumes of distribution at the steady state averaged 30% of body weight, and the rate of renal clearance was less than the rate of creatinine clearance (83 vs. 120 ml/min), a finding that indicates tubular reabsorption. The rate of serum clearance was greater than the rate of renal clearance (100 vs 83 ml/min). Urinary excretion in 24 hr averaged 94% of the dose, and there was no binding of serum proteins. In another cross-over study, volunteers received single intramuscular injections of these antibiotics. Peak concentrations of drug in serum after 45 min to 2 hr averaged 19.9 and 19.0 mug/ml for amikacin and kanamycin, respectively. Serum half-lives between 4 and 8 hr after administration of drug were 2 hr, and an average of 94% of the dose was recovered in the urine in 24 hr. Thus, the pharmacologic properties of amikacin and kanamycin were virtually identical.


Pharmacokinetics of amikacin in patients with normal or impaired renal function: radioenzymatic acetylation assay. The acetylating radioenzymatic assay was used for determination of levels of amikacin in serum and urine. Because of an inhibitor present in various amounts in urine, assay of amikacin in urine by this method requires added internal standards and thus is less precise than the assay in serum. Determination of the rate of plasma clearance, half-life, and volume of distribution of amikacin in 10 patients with normal renal function, four patients undergoing dialysis, and five patients with end-stage renal diseases have shown a relation of half-life (t1/2 in hr) to rate of clearance of serum creatinine (Cer) of t1/2 = 3 X Cer, the same relation as found for kanamycin and gentamicin. The apparent steady-state volume of distribution of amikacin in patients with diminished renal function is slightly, but not significantly, larger than that in normal patients; the values were 0.28 +/- 0.10 and 0.21 +/- 0.10, respectively. In normal patients, 87% of the drug is excreted by the kidney.


Pharmacokinetics of amikacin in patients with renal insufficiency: relation of half-life and creatinine clearance. The half-life of amikacin after a single intramuscular injection was determined in patients with severe renal failure who received 3.75 mg of drug/kg and in patients with various degrees of renal function who received 7.5 mg of drug/kg. The relation of the half-life of amikacin to levels of serum creatinine is practically identical to that of kanamycin. However, although concentrations of serum creatinine remained practically unchanged, rates of creatinine clearance may by considerably decreased in older subjects. This decrease may result in overestimation of the rate of glomerular filtration and subsequent overdosage. Therefore, the half-life of amikacin should be derived from values of rates of creatinine clearance or be predicted with use of a nomogram. The calculated half-life values may be used for development of appropriate dosage schedules for patients with various degrees of renal function. Such schedules would ensure therapeutic levels of drug and avoid potentially toxic accumulation of antibiotic.


Pharmacokinetics of amikacin in patients with impaired renal function. Pharmacokinetic parameters were determined after a single intramuscular injection of 7.5 mg of amikacin/kg to 10 volunteers with impaired renal function (creatinine clearance rate, 2.2-65ml/min per 1.73 m2) and to six volunteers with normal renal function. The mean peak concentrations of amikacin in sera of the two groups did not differ significantly from each other and exceeded by two to five times the reported in vitro minimal inhibitory concentrations for the majority of Pseudomonas aeruginosa and Enterobacteriaceae strains. There was a significant linear relation between the elimination rate constant of amikacin and the rate of creatinine clearance; there was a significant nonlinear relation between the half-life of amikacin and the serum creatinine concentration. Knowledge of these relations may aid in adjustment of the dosage of amikacin in patients with impaired renal function, especially when such information is used in conjunction with serum assays of amikacin.


Pharmacokinetics of amikacin for treatment of urinary tract infections in patients with reduced renal function. Amikacin (250 mg four times daily for 10 days) was administered intramuscularly to 22 patients with long-standing, severe infections of the urinary tract, in each case superimposed on chronic uropathy or nephropathy. Therapy with amikacin was completely successful in 14 patients (sterile 14-day follow-up urine specimens obtained by suprapubic needle aspiration of the bladder) and partially successful in three (sterile three-day but positive 14-day follow-up urine specimens). Five patients were judged to be treatment failures. Quantitative assessment of pyuria revealed a significant drop in the rate of excretion of white cells to near normal levels not only in patients who were cured but also in others, a finding which suggests that the infectious process had been affected by amikacin in all cases. The course of the disease in individual patients suggested that amikacin therapy can be successful after a long series of failures from treatment of such conditions with other antibiotics. Additional pharmacokinetic studies indicated that the half-life of amikacin may be increased five- to 10-fold in patients with renal insufficiency. A tentative dosage schedule was prepared for patients with various degrees of impaired renal function on the basis of average half-life values.


Amikacin in obstetric, gynecologic, and neonatal infections: laboratory and clinical studies. Based on the proportion of resistant, moderately sensitive, and sensitive strains, the descending order of activity of amikacin against clinical isolates of urinary pathogens was Salmonella, Klebsiella, Enterobacter, Escherichia coli, Staphylococcus aureus, Citrobacter, Proteus species, and Pseudomonas aeruginosa. However, amikacin was the most active of the antibiotics tested (including gentamicin and tobramycin) against 100 strains of P. aeruginosa. The calculated half-life of amikacin was substantially longer in patients with compromised renal function than in normal subjects. Immaturity of renal function, characteristic of the newborn, similarly slowed the rate of excretion of amikacin. The cure rate (complete clinical remission and eradication of the pathogen) was 91% in 22 patients with urinary tract infection (including 16 with chronic pyelonephritis) treated with 500 mg of amikacin every 8 or 12 hr for eight to 17 days. After single injections of 7.5 mg/kg 2-3 hr before delivery, appreciable amounts of the drug were recovered from the cord blood. No local or systemic intolerance or laboratory abnormalities were observed in a total of 42 patients (including eight infants) treated for a maximum of two weeks. No ototoxicity was demonstrable in any of the 12 patients subjected to audiometry; nystagmography revealed slight vestibular dysfunction in two elderly patients.


Preliminary clinical trial with amikacin in chronic recurrent gram-negative bacterial infections refractory to other antimicrobial agents. Eleven patients with 16 infections due to Enterobacteriaceae or Pseudomonas that were in most cases refractory to treatment with cephalosporins, kanamycin, gentamicin, tobramycin, carbenicillin, or ampicillin (administered singly or in combinations) received 1 g of amikacin daily by the intramuscular route (10 patients) or 0.4 g daily (one patient with renal insufficiency). The average duration of treatment was eight days. At the beginning of treatment, 18 pathogens were sensitive to amikacin at concentrations of 0.25-2 mug/ml. Of the 16 infections, 10 were cured clinically. Thirteen of the 19 pathogens isolated initially were eradicated, and five persisted during treatment but without change in in vitro sensitivity. A strain of Pseudomonas cepacia recovered from a diabetic patient and sensitive initially to 8 mug of amikacin/ml showed an eightfold increase in minimal inhibitory concentration. Superinfection with P. cepacia resistant to amikacin was noted in one case and urinary colonization with Candida albicans in another. No abnormalities of hematopoietic, hepatic, or renal function were observed in laboratory tests.


Clinical and laboratory studies with amikacin in newborns, infants, and children. Thirty (86%) of 35 infants and older children with proven gram-negative sepsis had a complete clinical remission after treatment with amikacin. In 27 (82%) of 33 infectious episodes for which bacteriologic results were available before and after treatment, the organism was eradicated. The dosage of amikacin was either 7.5 mg/kg or 15 mg/kg given intramuscularly at 12-hr intervals. No adverse clinical effects or laboratory abnormalities were observed during treatment, which lasted from five to 14 days. All bacteria were sensitive to amikacin when tested by the disk diffusion method, and all but a single strain of Pseudomonas were sensitive when tested by the agar dilution method. Assays of serum and urine demonstrated adequate levels of amikacin after single intramuscular injections of 3.75 or 7.5 mg/kg; simultaneous assays of serum and cerebrospinal fluid in two cases demonstrated comparable concentrations of drug suggestive of a high degree of penetration into the cerebrospinal fluid in two cases demonstrated comparable concentrations of drug suggestive of a high degree of penetration into the cerebrospinal fluid during infection. Serial measurements of amikacin in serum from 0.5 to 12 hr after administration of single doses of 7.5 mg of drug/kg to six newborns revealed no significant differences in the concentrations achieved with intramuscular or intravenous administration of the drug.


Amikacin for treatment of infections in patients with malignant diseases. Amikacin was evaluated in patients with malignant diseases during 134 episodes of identified infection, most of which were cases of pneumonia and septicemia. The overall rate of response of the identified infections was 63%. The majority of infections were caused by Escherichia coli, the Klebsiella-Enterobacter-Serratia group, and Pseudomonas aeruginosa. The response rate for infections caused by these organisms was 80%. Five of eight infections caused by organisms resistant to gentamicin responded to therapy with amikacin. Nephrotoxicity was observed in 13% of patients who had normal renal function initially.


Amikacin therapy for severe gram-negative sepsis: efficacy in infections involving gentamicin-resistant organisms. Thirty-eight patients with 41 serious infections due to gram-negative bacteria were treated with amikacin. Twenty of these infections involved organisms that were resistant to gentamicin. The results of therapy in 31 of the infections satisfied the criteria for bacteriologic and clinical cure. Eight patients with urinary tract infections and obstructive uropathy had a good clinical response, but routine follow-up cultures of urine at 30 days were positive. Two patients had persistent sepsis and were considered therapeutic failures. Toxicity to the eighth nerve was documented in three of 31 patients for whom routine audiometric testing was performed. These results indicate that amikacin is effective in the treatment of serious infections due to gram-negative bacilli and is particularly useful in infections involving resistant organisms.


A new look at the plasma disappearance of sulfobromophthalein (BSP): correlation with the BSP transport maximum and the hepatic plasma flow in man. In order to improve the clinical usefulness of the plasma disappearance curve of sulfobromophthalein (BSP), its components were analyzed in 26 control subjects, in 28 patients with cirrhosis, and in 13 cases of miscellaneous liver abnormalities. The uncorrected initial disappearance rate (ki) was found to discriminate best between the control and the patient groups. The second exponential component (k2) was linearly correlated with the transport maximum (Tm) on a double logarithmic plot, but appeared to be independent of the estimated hepatic plasma flow (EHPF). An interpretation of this relationship was possible, when based on a model having saturation kinetics for biliary excretion. The first exponential component (ki) appeared primarily determined by hepatic perfusion. These relationships may contribute to a better understanding and more rational use of dye excretion tests as measures of hepatic function. The data also add to our knowledge about the nature of the excretory defect in cirrhosis.


Minoxidil reduces pulmonary vascular resistance in dogs and cattle. Minoxidil has a direct dilator effect on the systemic arterial smooth muscle. It is potentially an important drug in the treatment of systemic hypertension, especially when combined with beta blockade, which is used to control the associated tachycardia and increase in cardiac output. However, recent observations have suggested that minoxidil might cause pulmonary hypertension. Consequently, we examined the acute effect of monoxidil and propranolol, separately and in combination, on the pulmonary vasculature of the anesthetized dog and the awake calf during normoxia and hypoxia. In both species minoxidil reduced pulmonary vascular resistance. In the dogs this appeared to be the result of a direct action on the pulmonary vascular smooth muscle and in the cattle it was secondary to beta-receptor stimulation. Propranolol alone in the cattle increased the pulmonary pressor response to hypoxia. While we have not examined the possibility that chronic administration of minoxidil might cause pulmonary hypertension by some other mechanism, our acute studies suggest that it reduces, rather than increases, pulmonary vascular resistance. Furthermore, there seems to be a species difference in the mode of its action in dogs and cattle.


The natriuretic effect of the organic acid para-aminohippurate. Infusion of para-aminohippurate (PAH) during renal clearance experiments has been shown to increase urinary sodium excretion (UNAV). In addition, it has recently been suggested that accumulation of PAH and/or related compounds may be responsible for the increased UNAV per nephron in chronic renal failure. Therefore, studies were designed to determine the mechanism for the natriuretic effect of PAH. PAH administration at (0.19 mM per minute) into the dog renal artery led to an average increase in UNAV of 56+/-11 muEq per minute. Mannitol given at this rate (0.19 mM per minute) led to an increase in UNAV of 26+/-10 muEq per minute, which was less than the increase in UNAV with PAH. NA2SO4 given at this (0.19 mEq per minute) or a higher rate (0.60 mEq. per minute) was associated with an increase in UNAV of 53+/-18 and 228+/-38 muEq per minute, respectively. In the PAH and SO4 studies the increase in UPAHV or USO4V was not different from the increase in UNAV. These results suggest that the natriuretic effect of PAH is mainly due to its effect as a nonreabsorbable anion and offer no support for an osmotic effect or a direct effect on active sodium transport.


Phytosterols in aortic tissue in adults and infants. Relationships between aortic tissue phytosterols and cholesterol in five adults, five infants, two neonates, and one 30 week abortus were studied. In the normal aortic tissue of the abortus and two neonates, tissue cholesterol levels were 0.67, 0.08, and 0.89 mg. per gram of wet weight, respectively; tissue phytosterol levels were as follows: compesterol (0.94, 0.62. 1.8), stigmasterol (0.18, 0.54, 0.80) and beta-sitosterol (0.78, 1.84, 2.80) mug per gram of wet weight. In 11 aortic tissue samples from five infants studied at 3, 4, 6, 6, and 36 months of age, all having been on phytosterol-rich formulas, mean aortic cholesterol was 0.66 mg. per gram, campesterol 3.57, stigmasterol 9.22, and beta-sitosterol 8.93 mug per gram. In the 11 aortic samples from five infants, mean (+/-S.E.) tissue stigmasterol (9.2+/-2.7) and beta-sitosterol ((8.9+/-1.3) were greater than mean levels (0.51+/-0.18 and 1.8+/-0.6) in the four aortic sections from the abortus and two neonates. Mean (+/-S.E.) cholesterol in the 11 aortic sections from five infants (0.66+/-0.11) was not significantly higher than cholesterol (0.55+/-0.24 mg. per gram) in the four aortic sections from the abortus and two neonates, but was considerably higher than the tissue cholesterol level of 0.08 mg. per gram in one of the two neonates. Mean (+/-S.E.) cholesterol in 11 normal aortic tissue sections from five adults (3.4+/-0.7 mg. per gram) was higher than in the five infants, whereas mean compesterol, stigmasterol, and beta sitosterol, respectively 14, 13, and 16 mug per gram, were somewhat higher but generally comparable to infant levels. In five aortic tissue samples from mature atheromatous plaques in two adults, cholesterol was 54 mg. per gram and mean campesterol, stigmasterol, and beta-sitosterol were, respectively, 112, 167, and 236 mug per gram. In 15 aortic tissue samples from five adults, cholesterol correlated closely with stigmasterol, r=0.865, beta-sitosterol, r=0.918, and with total phytosterols, r=0.938, p less than 0.01, but not with campesterol, r=0.448. In 11 aortic tissue samples from five infants, cholesterol did not correlate with campesterol, r=0.005, stigmasterol, r=0.006, beta-sitosterol, r=-0.099, or total phytosterols, r=-0.045. Prior to birth some phystosterols apparently cross the placenta. In the first several months of life, vegetable-oil formula-fed infants accrue plant sterols in their aortic tissues. Moderate amounts of phytosterols are present in mature atheromatous lesions in adults. The implications of these findings are unknown and their relationship to deposition of cholesterol in atheromatous and in normal aortic tissues remains to be elucidated.


Removal of heparin and protamine from plasma. A simple chromatographic technique for rapid adsorption of heparin and protamine from plasma samples is described, allowing accurate interpretation of coagulation screening tests and specific clotting factor assays. With the use of columns of ECTEOLA-cellulose, up to 300 U. of heparin could be completely adsorbed from a 1 ml. plasma sample. When citrated nonheparinized plasma was passed over the ECTEOLA-cellulose columns, the thrombin, prothrombin, and partial thromboplastin times were unaffected. Levels of fibrinogen, prothrombin, and factors V, VII, VIII, IX, and XI average within 90 per cent of control, nonchromatographed samples. When heparinized plasma samples (0.1 and 1.0 U. per milliliter) were passed over columns, heparin was completely removed and the results of the screening tests and the specific factor assays were the same as for the chromatographed nonheparinized samples. In addition, heparinized samples with decreased factor VIII activity maintained their pretreatment factor VII activities after heparin removal. Blood samples containing heparin were obtained from two patients during open-heart surgery. Following heparin adsorption on ECTEOLA-cellulose columns, factor VIII activity levels remained above 60 per cent during cardiopulmonary by-pass. The presence of protamine sulfate in plasma samples prolonged the prothrombin and partial thromboplastin times while slightly shortening the thrombin time. The protamine effect persisted after ECTEOLA-cellulose, but could be removed by a similar column of carboxymethyl-cellulose. The latter resin had no effect on screening tests or on assays of factors VIII or IX activity. The combination of the two resins was then used to remove the separate inhibitory effects from heparinized plasma samples to which protamine had been added.


The effects of hemorrhage, hypoxia, and a preparation of erythropoietin on thrombopoiesis. The effects of hemorrhage, hypoxia, or a preparation of erythropoietin on platelet production were investigated by measuring incorporation of selenomethionine-75Se (75SeM) into the platelets of rabbits or mice. Rabbits that were bled daily for 5 days had a significant increase in the platelet count, 48 hours after cessation of hemmorrhage, that coincided with a threefold increase in isotope incorporation into platelets. Mice that were bled daily for 3 days also had significantly higher platelet counts and a 38 per cent increase in incorporation of isotope into platelets, 3 days after the last hemorrhage. Normal rabbits, injected with plasma from repeatedly bled, anemic, and moderately thrombocytopenic rabbits, had a 58 per cent greater maximum incorporation of 75SeM than did control animals. Mice exposed to hypoxia for 6 days had a mean platelet count 23 per cent lower than normal controls, but no change in incorporation of 75SeM into platelets. Plasma from hypoxic mice did not stimulate platelet production when injected into normal mice. A preparation of human urinary erythropoietin (15 to 30 U. per mouse or 30 to 120 U. per rabbit) significantly increased incorporation of isotope into the platelets of normal mice and rabbits. The results demonstrated that hemorrhage, but not hypoxia, is associated with increased thrombopoietic activity in plasma. However, large doses of preparations of human erythropoietin contained detectable thrombopoietic activity.


Effect of indomethacin and sodium meclofenamate on the renal concentrating defect in experimental enterococcal pyelonephritis in rats. The present studies have confirmed a severe urinary concentrating defect early in the course of experimental enterococcal pyelonephritis. This defect in maximum concentrating ability was almost completely reversed immediately following indomethacin or sodium meclofenamate intravenously. This effect of indomethacin and sodium meclofenamate was transient and was not associated with a fall in numbers of enterococci per gram of kidney. Injection of indomethacin or sodium meclofenamate in noninfected rats had no effect on maximum renal concentrating ability. The potential mechanisms by which indomethacin and sodium meclofenamate, inhibitors of renal prostaglandin synthesis, could reverse a defect in maximum urinary concentration are discussed.


The effect of hemodialysis on neutrophil chemotactic responsiveness. Fifteen patients with chronic renal failure had depressed neutrophil chemotactic responsiveness following several hemodialysis treatments. The chemotactic index (C.I.) of these patients was 12.7+/-6.4 as compared with 72.8+/-22.7 for controls (p less than 0.001). Patients with chronic renal failure, not on hemodialysis, had only mildly depressed neutrophil chemotactic responsiveness (42.3+/-15;p less than 0.01). Thus, hemodialysis impairs neutrophil function and may contribute to the increased risk of infection in uremic patients. Chemotactic responsiveness returned to normal in three patients following renal transplantation.


Effect of antecedent hormone administration on lipolysis in the perifused isolated fat cell. Development of a perifusion system utilizing isolated fat cells (IFC) has converted the static incubation system into one capable of measuring dynamic changes in adipose tissue metabolism. Using this new system, we have studied the initiation by epinephrine and inhibition by insulin of lipolysis in IFC. Perifusion with "low" (10 muU per milliliter) or "high" (50 muU per milliliter) insulin was performed (1) prior to, (2) simultaneous with, and (3) after infusion of epinephrine. Exposure to low insulin prior to or simultaneously with epinephrine produced a greater amount of antilipolysis than the addition of insulin to cells already stimulated by epinephrine. Similar results were obtained with proinsulin. Insulin (50 muU per milliliter) when given prior to or simultaneously with 0.035 mug per milliliter of epinephrine bitartrate completely blocked lipolysis but the antilipolytic effect of insulin could be overcome by increasing the concentration of epinephrine bitartrate. Insulin (50 muU per milliliter) also decreased the sensitivity of the fat cells to subsequent doses of epinephrine bitartrate even after apparent removal of all immunoreactive insulin by continuing buffer infusion. After exposure to 50 muU per milliliter of insulin, followed by buffer alone, the cells failed to release glycerol in response to 0.035 mug per milliliter of epinephrine bitartrate but did respond to 3.5 mug per milliliter of epinephrine bitartrate. Thus, the sequence of hormonal administration as well as hormonal concentration greatly altered the responsiveness of the adipose tissue to both lipolytic and antilipolytic stimuli.


Stapedectomy. A non-personal series.

Stapedectomy. A non-personal series. An attempt has been made to indicate from St. Thomas' Hospital what the likely outcome of stapedectomy would be when performed by a cross-section of the speciality at differing levels of training, and to indicate the complications encountered at this centre. Included in the review is a comparison of the results from polythene struct and vein graft replacement and piston replacement.


Delayed hypersensitivity skin test in head and neck cancer. A brief introduction is given stressing the importance of host reactions against tumour specific antigens. Two groups of patients are presented. Positive tests are associated with a better prognosis in both groups. Energy is commonly associated with widespread disease, but other factors appear to be concerned as well. Immune competence is impaired soon after surgery, but as time progresses this appears to recover. Tumour bulk appears to be the biggest barrier to the immune mechanism and it would appear that the role of immunotherapy in the future will be to supplement more conventional methods of treatment, especially surgery.


Chondromyxoid fibroma of the petrygo-palatine space. A patient who for five years had obstinate unilateral facial pain, difficult to interpret, was found to have an expanding process in the left retromaxillary space. Histological examination of a biopsy specimen revealed chondromyxoid fibroma. This tumour is rarely seen in the bones of the face and has never before been described in this area. The clinical and histological findings are described and discussed.


Secretory otitis media due to a hair-bearing dermoid of the mastoid cavity. A case of persistent unilateral secretory otitis media occurring in an elderly patient is described. The aetiology of the condition proved to be due to a dermoid lying in the mastoid cavity. The clinical, radiological and histological features are described, with comments as to the association which might have existed linking these two conditions. Comment is made concerning the aetiology of dermoid cysts within the mastoid antrum.


Mechanism of lipolysis induced by electrical stimulation of the hypothalamus in the rabbit. Electrical stimulation of the ventro-medial hypothalamus of the rabbit elevated plasma glycerol concentration. This elevation was suppressed by treatments of the animals with hexamethonium and propranolol, or by adrenalectomy, but was not suppressed by treatments with atropine and phentolamine. These results would indicate that the effect of electrical stimulation of ventro-medial hypothalamus is mainly mediated by catecholamine(s) liberated from the adrenal medulla and acts on beta-receptor of adipose tissue.


Ionic requirements for the active ileal bile salt transport system. Taurocholate transport by everted ileal gut sacs was studied in physiological media containing graded amounts of sodium ions. Significant uphill transport of taurocholate was observed when the bulk of NaCl was replaced by osmotic equivalents of mannitol or choline chloride. Seventy-seven percent of control transport activity was observed when 36 milliequivalents per liter of Na+ were present in the incubation medium with mannitol acting as the isosmotic replacement, and 74% of the control transport was retained when 31 milliequivalents per liter of Na+ were present in the incubation medium with choline chloride acting as the osmotic replacement. Lowering the Na+ concentration to 19 milliequivalents per liter (i.e., 84% replacement of Na+) still allowed for 69% of the uphill transport observed in the control incubations. Taurodehydrocholate transport by ileal everted sacs was more sensitive to decreased Na+ concentrations; 29% of control transport was observed at 31 milliequivalents per liter of Na+. A kinetic analysis comparing the transport of taurocholate with taurodehydrocholate, the triketo analogue, at different concentrations of Na+ indicated that the apparent affinity of the transport system for Na+ is greater in the presence of taurocholate than in the presence of taurodehydrocholate. The ability of taurodehydrocholate to depress taurocholate transport is less in media of low Na+ concentration. Finally, in vivo intestinal perfusion studies demonstrated that the depression of taurocholate absorption, following Na+ removal, is reversible. These results are in agreement with the idea that Na+ has a physiological role in intestinal bile salt transport, and that the affinities of the anionic bile salt and the sodium cation for the transport system appear to be cooperative in that one enhances the binding of the other.


Insulin binding and insulin response of adipocytes from rats adapted to fat feeding. The effect of fat feeding on adipocyte insulin binding was examined to expand a study of adaptive changes in plasma membrane functions. Cells from rats fed a high fat (L) diet for five to seven days bound less insulin and showed a decreased response to insulin (glucose oxidation) compared to those from rats fed a high glucose (G) diet. Both high and low affinity sites were influenced; the extent of the binding difference increased as increasing concentrations of insulin were present in the assay medium. Diet did not change hormone degradation on the capacity of phospholipase C to increase binding. Concanavalin A effects on fat cells were also decreased by L diet both in inhibition of insulin binding and its insulin-like effect on glucose oxidation. Spermine, which had no effect on insulin binding, also had a smaller insulin-like effect on glucose oxidation by L cells than by G cells. Serum insulin was significantly lower (30 +/- 3.7 muU/ml) in L than in G (43 +/- 3.1 muU/ml) groups. Dietary fat produces alterations in fat cells that decrease insulin binding as a part of a complex overall adaptation to the diet.


Circadian distribution of bile acid in the enterohepatic circulatory system in hamsters. The distribution of bile acid in the enterohepatic circulatory system at different times of the day was determined in 48 hamsters exposed to a rigid light schedule (6 AM to 6 PM) and fed, ad libitum, for 4 weeks. In each portion of the enterohepatic circulatory system, the relative amount of bile acid was determined 24 hours after an intraperitoneal administration of [3H]taurocholic acid by comparing the radioactivity recovered from that portion with the total radioactivity remaining in the entire system. A circadian fluctuation of the relative bile acid content (percent of total) was observed in serum, liver, gallbladder, and intestinal contents. The patterns of such rhythmic change varied in various segments of the intestinal tract but correlated well with the time sequence of the movement of bowel content. Rhythms in the serum and liver were intimately related to the intestinal absorption of bile acid. Due to its small capacity, the gallbladder played only a minor role in the regulation of such a rhythm.


A biosynthetic method for the preparation of high specific activity 32P-labeled phospholipids. 32P-Labeled phospholipids with specific activities up to 400 mCi/mmole as well as [32P]CDP-choline were prepared by cultivation of mouse fibroblasts or mouse Ehrlich ascites cells in the presence of [32P]orthophosphate. The method was also used to prepare [methyl-3H]choline-labeled glycerophospholipids from [3H]choline. The yields and the specific activities of the phospholipids were significantly lower when preparations of ox white blood cells were used.


Metabolism of glycerol monoethers in cultured liver cells and implications for monoglyceride pathways. A comparative study has been made of the assimilation and metabolism of rac-1 and 2-[9, 10(-3)H]-octadec-9-enylglycerol in a clone of epithelial-like cells isolated from rabbit liver. Based on cell protein content, the free glycerol ether isomers attained equal cellular concentrations. As shown by isolation and degradation experiments, however, the incorporation of radioactive 1-monether was appreciably higher than that of radioactive 2-monoether in both the triacylglycerol and phospholipid fractions. The 1-monoether, unlike the 2-monether, was also a significant source of esterified fatty acids in both lipid fractions. In addition, the 1-monoether, but not the 2-monoether, was an active precursor of plasmalogens, particularly ethanolamine plasmalogen. In contrast to the 1-monoether, the 2-monoether was a more active precursor of triacylglycerols than it was of phospholipids. The results indicate that in the rabbit liver cells the pathway of complex lipid synthesis from 1-monoether was via 1-alkyl-sn-glycerol-3-phosphoric acid and from 2-monoether via 1-alkyl-2-acyl-sn-glycerol.


Artifacts produced during acid-catalyzed methanolysis of sterol esters. Sterol esters were transesterified within 1 hr using either acid or base catalysts. Acid-catalyzed methanolysis of sterol esters with HCl, H2SO4, or BF3 leads to the formation of two artifacts derived from the sterol portion of the molecule; they were identified as dehydrated and methoxylated derivatives of sterols. These two artifacts were not produced using a base-catalyzed methanolysis with NaOCH3.


Receptor units responding to movement in the octopus mantle. 1. A preparation of the mantle of Octopus which is inverted over a solid support and which exposes the stellate ganglion and associated nerves is described. 2. Afferent activity can be recorded from stellar nerves following electrical stimulation of the pallial nerve. The latency and frequency of the phasic sensory response is correlated with the contraction of the mantle musculature. 3. It is proposed that receptors cells located in the muscle, and their activity following mantle contraction, form part of a sensory feedback system in the mantle. Large, multipolar nerve cells that were found between the two main layers of circular muscle in the mantle could be such receptors.


Flow visualization with stereo shadowgraphs of stratified fluid. Water stratified thermally or with dissolved material has a refractive index that varies with height. The stratification has no obvious visual effect until the fluid is disturbed, for example by a fish, but then it marks the creature's wake with a jump in refractive index that is visible in shadowgraphic projection. Two shadowgraphs in stereo display the wake in three dimensions. For a permanent record, or for analysing events too quick for the eye to follow, movies can be taken of the shadowgraphs.


Evidence for a synaptically mediated decrease in conductance in a crustacean myocardium. 1. In the neurogenic heart of the isopod Porcellio dilatatus, electrical stimulation of the cardio-regulatory nerves at rates greater than 20-25 pulses/s elicited inhibitory junctional potentials (IJPs) in the myocardium. Its cessation was followed by a long lasting hyperpolarization of myocardial membrane (post-stimulus hyperpolarization = PSH). 2. During the PSH the membrane resistance of the heart muscle increased. The PSH was enhanced by myocardium hyperpolarization, decreased by depolarization and reversed around -50 mV. 3. Picrotoxin inhibited the summated IJPs elicited by the stimulation and thus caused the membrane to maximally hyperpolarize during inhibitory train, thus suggesting a composite nature of the inhibitory processes. 4. The PSH was reversibly reduced in K+-free saline or in ouabain containing saline but partial restoration was obtained by injection of inward current to the myocardium. 5. The PSH was abolished in lithium saline and reduced in Na+-deficient (choline) solution. Cl-deficient solution that markedly affected the summated IJPs shortly after its introduction did not affect the PSH. 6. It is proposed that the PSH results from a decrease in conductance, presumably to both Na+ and K+. The implication of such a mechanism as a component of the inhibitory regulation of this crustacean heart is discussed.


Heat transfer between fish and ambient water. 1. The ability of fish gills to transfer heat was measured by applying a heat pulse to blood in the ventral aorta and measuring it before and after passing through the gills of a teleost, Hemitripterus americanus. 2. 80-90% of heat contained in the blood is lost during passage through the gills. 3. The fraction of heat not lost during passage through the gills is due to direct transfer of heat between the afferent and efferent artery within the gill bar. 4. The major fraction of metabolic heat (70 - 90%) is lost through the body wall and fins of the sea raven in sea water at 5 degrees C; the remainder is lost through the gills.


The effect of size on the fast-start performance of rainbow trout Salmo cairdneri, and a consideration of piscivorous predator-prey interactions. The fast-start (acceleration) performance of seven groups of rainbow trout from 9-6 to 38-7 cm total length was measured in response to d.c. electric shock stimuli. Two fast-start kinematic patterns, L- and S-start were observed. In L-starts the body was bent into an L or U shape and a recoil turn normally accompanied acceleration. Free manoeuvre was not possible in L-starts without loss of speed. In S-starts the body was bent into an S-shape and fish accelerated without a recoil turn. The frequency of S-starts increased with size from 0 for the smallest fish to 60-65% for the largest fish. Acceleration turns were common. The radius of smallest turn for both fast-start patterns was proportional to length (L) with an overall radius of 0-17 L. The duration of the primary acceleration stages increased with size from 0-07 s for the group of smallest fish to 0-10 s for the group of largest fish. Acceleration rates were independent of size. The overall mean maximum rate was 3438 cm/s2 and the average value to the end of the primary acceleration movements was 1562 cm/s2. The distance covered and velocity attained after a given time for fish accelerating from rest were independent of size. The results are discussed in the context of interactions between a predator and prey fish following initial approach by the predator. It is concluded that the outcome of an interaction is likely to depend on reaction times of interacting fish responding to manoeuvres initiated by the predator or prey. The prey reaction time results in the performance of the predator exceeding that of the prey at any instant. The predator reaction time and predator error in responses to unpredictable prey manoeuvre are required for prey escape. It is predicted that a predator should strike the prey within 0-1 s if the fish are initially 5-15 cm apart as reported in the literature for predator-prey interactions. These distances would be increased for non-optimal prey escape behaviour and when the prey body was more compressed or depressed than the predator.


Aerodynamics, kinematics, and energetics of horizontal flapping flight in the long-eared bat Plecotus auritus. The kinematics, aerodynamics, and energetics of Plecotus auritus in slow horizontal flight, 2-35 m s-1, are analysed. At this speed the inclination of the stroke path is ca. 58 degrees to the horizontal, the stroke angle ca. 91 degrees, and the stroke frequency ca. 11-9 Hz. A method, based on steady-state aerodynamic and momenthum theories, is derived to calculate the lift and drag coefficients as averaged over the whole wing the whole wing-stroke for horizontal flapping flight. This is a further development of Pennycuick's (1968) and Weis-Fogh's (1972) expressions for calculating the lift coefficient. The lift coefficient obtained varies between 1-4 and 1-6, the drag coefficient between 0-4 and 1-2, and the lift:drag ratio between 1-2 and 4-0. The corresponding, calculated, total specific mechanical power output of the wing muscles varies between 27-0 and 40-4 W kg-1 body mass. A maximum estimate of mechanical efficiency is 0-26. The aerodynamic efficiency varies between 0-07 and 0-10. The force coefficient, total mechanical power output, and mechanical and aerodynamic efficiencies are all plausible, demonstrating that the slow flapping flight of Plecotus is thus explicable by steady-state aerodynamics. The downstroke is the power stroke for the vertical upward forces and the upstroke for the horizontal forward forces.


Neural excitation of the larval firefly photocyte: slow depolarization possibly mediated by a cyclic nucleotide. 1. In firefly larvae, extracellular recordings from the light organ nerve show that a volley of action potentials elicits a glow of an intact animal. 2. Intracellular recordings from the photocytes show that they respond to nerve stimulation with a slow, graded depolarization which precedes light emission. The depolarization begins about 0-5 s after the nerve is stimulated; it peaks about 1 s after stimulation; and subsides about 2-5 s after the stimulus. The glow increases fastest when the photocyte depolarization is at its peak and lasts 5-15 s. 3. Photocyte depolarization is associated with a decrease in the input resistance of the cell. 4. Adrenergic receptors in the light organ are pharmacologically similar to vertebrate alpha-receptors. 5. Phophodiesterase inhbitors, aminophylline and theophylline, cause the light organ to glow, suggesting that cyclic nucleotides may mediate the effect of the adrenergic nerve transmitter.


Role of proprioceptive feedback from nonspiking mechanosensory cells in the sand crab, Emerita analoga. The two programmes underlying uropod beating in Emerita ('swimming' and 'treading water') are distinguished by a difference in timing of the power stroke within the interval between return strokes (cycle). While 'swimming' (cycles approx. 80-400 ms) the phase and while 'treading water' (cycles approx. 100-700 ms) the latency of the power stroke are relatively invariant. Analyses of electromyograms of untrestrained Emerita, before and after bilateral surgical ablation of the four nonspiking mechanoreceptive cells associated with each uropod, established that power strokes in 'treading water' are dependent upon proprioceptive feedback from the nonspiking cells. As cycle duration increases from 80 to 700 ms, the function of the reafference changes from reinforcement of the centrally generated 'swimming' pattern to production of the 'treading water' pattern.


Stretch-sensitive neural units in the body wall of the earthworm, Lumbricus terrestris L. 1. Sensory neural units responding to sinusoidal stretching of the body wall were studied in the earthworm, Lumbricus terrestris L. 2. A phasic stretch-sensitive unit found in segmental nerve I responded optimally to stretching at frequencies of 4-6/min. 3. The number of spikes per stretch and the spike frequency in the unit were directly related to the amplitude of the applied stretch within a range of 0-2-0-7 mm stretch/segment. 4. The ranges of amplitude and frequency sensitivity for the unit in isolated preparations corresponded closely to stretch parameters seen during peristaltic locomotion in intact animals. 5. Stretch-sensitive responses in segmental nerve II-III were more variable; some units responded to longitudinal stretch while others responded to relaxation.


A 'TEA+-insensitive' mutant with increased potassium conductance in Paramecium aurelia. A single-gene mutant of Paramecium aurelia is analysed electrophysiologically. (a) The regenerative Ca-response, triggered by small or moderate current, was smaller and slower in the mutant than in wild type. (b) Input resistance of the mutant membrane is about half of that of wild type bathed in various solutions. This is true for the zero-current input resistance and the chord resistance measured with high depolarizing current. (c) Membrane resistance of the mutant measure with hyperpolarizing currents is smaller than that of wild type only when K+ is the major external cation. (d) Internally applied TEA+ or externally applied Ba+ increases the membrane resistance of the mutant to that of wild type similarly treated. We conclude that the mutant has an increased K conductance.


Adult motor patterns produced by moth pupae during development. Muscle potentials were recorded extracellularly from developing pupae and adults of the saturniid moths Antheraea polyphemus and A. pernyi and the sphingid moth Manduca sexta. During the week prior to the terminal ecdysis, developing moths still enclosed within the pupal cuticle produced motor patterns similar to those recorded from adults during flight and shivering. The pupal patterns had a longer cycle time and were more variable than the adult motor patterns. Characteristic inter-family differences in adult motor patterns were apparent in pupal motor patterns. Development of motor patterns was followed over several days by observing individuals with chronically implanted leads. Early in the pupal period potentials were small and infrequent. The amount of activity gradually increased and became more patterned. As development proceeded adult patterns were produced for increasing lengths of time, although the patterns changed quickly and spontaneously. Restricting the wing movements of A. polyphemus adults increased the cycle time, increased the number of spikes per burst in muscles opposing the restraint, and did not alter the interspike interval within a burst. The flight patterns produced by pharate moths, in which the wings are also immobile, also have a longer cycle time than that of adult flight, but the number of spikes per burst the same and the interspike interval is longer than in adult flight. These observations suggest that the differences between pupal and adult patterns are not necessarily due to the confinement of the wings by the pupal cuticle.


Respiration of the amphibious fishes Periophthalmus cantonensis and Boleophthalmus chinensis in water and on land. 1. The routine oxygen consumption by Periophthalmus cantonensis and Boleophthalmus chinensis in water increased geometrically, whereas that in air increased logarithmically with temperature. At temperatures of more than 20 degrees C the oxygen uptake of both species was greater in water than in air. 2. When the fishes were able freely to select either an aquatic or terrestrial habitat, the total oxygen consumption of Periophthalmus and Boleophthalmus was 236 and 110 ml/kg, h at 20 degrees C respectively; 66% (Periophthalmus) and 70% (Boleophthalmus) of the total uptake was from water, and 34 and 30% of the total uptake was from air at 20 +/- 1 degrees C. 3. Oxygen uptake of fish limited to aquatic or terrestial life was less than when they could freely select their habitat; for Periophthalmus, uptake was reduced to 83% when confined in water and to 50% in air, and for Bolephthalmus, to 65% in water and to 43% in air. 4. The proportion of oxygen uptake by the gill in water was 52% for Periophthalmus and 59% for Boleophthalmus; in air the corresponding figures were 27 and 52%. 5. The proportions of oxygen uptake via the skin in water was 48% for Periophthalmus and 36% for Boleophthalmus; in air the corresponding figures were 76 and 43%. 6. It is concluded that, on land, Periophthalmus relies mainly on its skin and Boleophthalmus relies mainly on its gills.


Decline in the growth potential of spleen-colonizing bone marrow stem cells of long-lived aging mice. The growth capacity of femoral bone marrow stem cells from young and old long-lived mice was assessed in the spleen of X-irradiated young and old syngeneic recpients by determining: (a) the number of stem cells colonizing the spleen, (b) the rate of incorporation of 125I-labeled iododeoxyuridine by proliferating colony cells, and (c) the number of cells present in the largest colonies at the end of the growth phase.We found that the growth capacity of stem cells declined with age. We further found that the spleen-seeking and spleen colony growth capacities of old stem cells remained characteristically old even after they were allowed to self-replicate in the bone marrow of young recipients for an extended period of time. On the other hand, the spleen colony growth capacity of young stem cells could be reduced by allowing them to self-replicate in old recipients. These results suggest that the growth capacity of old stem cells is an intrinsic characteristic which cannot be readily altered, but that of young stem cells can be aged in an accelerated manner by allowing them to self-replicate in old recipients. An additional reduction was noted in the frequency of both young and old stem cells colonizing the spleen of old recipients and in the cell density of the largest colonies produced. These results indicate that factors extrinsic to the stem cells are also responsible for the decline with age in their spleen colony growth capacity.Thus, the growth capacity of old stem cells in old recipients could be as low as 10% that of young stem cells in young recipients.


Antibody-mediated suppression of grafted lymphoma. IV. Influence of time of tumor residency in vivo and tumor size upon the effectiveness of suppression by syngeneic antibody. In the suppression of the growth of a mouse lymphoma 6C3HED by antibody, the effectiveness of antibody in suppressing growing or established tumor cells and comparable number of freshly injected tumor cells is quantitatively similar. The effectiveness of antibody diminishes markedly when the number of tumor cells per mouse reaches the level of 10(6) due to the development of a macrophage shortage. At the 10(5) tumor cells level, antibody-mediated suppression takes place in an optimal manner and between 10(5) and 10(4) tumor cell numbers, the amount of antibody required to suppress 50% of the tumor cells is directly proportional to the number of tumor cells suppressed.


The pathogenesis of experimental membranous glomerulonephritis induced with homologous nephritogenic tubular antigen. The renal tubular epithelial antigen (Tub-Ag) of rats was solublized by Pronase and purified by gel filtration and acrylamide gel electrophoresis. Purified Tub-Ag was a glycoprotein with S20,W value of 8.4. Utilizing radiolabeled Tug-Ag, a sensitive radioimmunoassay for Tub-Ag and homologous antibody (anti-Tub-Ag) was developed. Tub-Ag activity associated with a protein of the same molecular size was demonstrated in the serum, as well as in Pronase extracts of all the organs tested, including kidney, liver, lung, spleen, intestine, stomach, and heart. The physiochemical properties of the Tub-Ag of rats and its distribution were essentially the same as the Tub-Ag of humans, which had been found in immune deposits in the kidney of some patients with idiopathic membranous glomerulonephritis. Rats were immunized with the purified Tub-Ag emulsified in Freund's complete adjuvant and followed for Tub-Ag and anti-Tub-Ag in the serum, as well as for proteinuria and immunohistological changes in the kidney. Serum Tub-Ag dropped sharply after 20 days, when anti-Tub-Ag appeared in the circulation. Persistent, massive proteinuria appeared still later, more than 30 days after injection, when anti-Tub-Ag disappeared and Tub-Ag reappeared in the serum of some of those rats. In others, anti-Tub-Ag in the serum persisted throughout the observation period of 90 days. The pathology of the kidney of the rats with proteinuria was that of a typical membranous glomerulonephritis; thickening of glomerular capillary walls with granular deposits of gamma-globulin and Tub-Ag was observed. On the basis of these results, Tub-Ag in the serum, probably released from cellular membranes of various organs as a physiological metabolite, is considered to maintain the pathological process in the kidney by providing the antigen continuously to form immune complexes.


Correlation of suppressor cell development in parental and F1 hybrid mouse strains with the growth of a parental tumor in vivo. Parental AKR/J, and AKB6F1 and AKD2F1 hybrid mice were injected subcutaneously with a spontaneously arising AKR/J tumor. The highly responsive AKB6F1 strain never exhibited any depression of immune functioning during the course of tumor growth and regression. The (AKR/J) intermediately responsive strain, while able to generate a successful anti-tumor response, did display a transient reduction of immunological capability, but only during the period tumor growth and not during tumor regression. Cells able to suppress antibody, but not cell-mediated responses, were found. The unresponsive AKD2F1 strain was characterized by both a marked depression of immune responsiveness, as well as the generation of suppressor cells to both antibody, and later, cell-mediated responses. Depression of immune responsiveness, and the generation of suppressor cells, appeared to correlate with the strength or weakness of the anti-tumor response in these strains of mice.


Analysis by a plaque assay of IgG- or IgM- dependent cytolytic lymphocytes in human blood. When monolayers of bovine erythrocytes (Eb) were exposed to purified human blood lymphocytes and either IgG or IgM fractions of rabbit anti-Eb serum, clear zones (plaques) appeared when Eb had been lysed by antibody-dependent effector cells (K cells). IgG-dependent plaque formation was complete by 20 h of incubation, while the IgM-dependent reaction required 40 h. The estimated minimal numbers of plaque forming cells (PFC) were 5.6% (IgG) and 2.0% (IgM) of the added lymphocytes. Inhibition experiments with human IgG or IgM indicated that different immunoglobulin receptors on the effector cells were involved in the two systems. In the IgG system, approximately 50% of the PFC had complement receptors and approximately 30% receptors for Helix pomatia A hemagglutinin (HP). In the IgM system, less than 10% of the PFC had complement receptors, while approximately 60% had HP receptors. The results suggest that a subset of human T cells had IgM-dependent K-cell potential. These cells are different from the majority of the IgG-dependent K cells.


Reaginic antibody produced in mice with contact sensitivity. Mice produced reaginic antibody within 1 wk of painting with the contact sensitizing agent picryl chloride. The titers, measured by passive cutaneous anaphylaxis in rats, increased after repeated applications of picryl chloride. In contrast, serum agglutinins did not increase after two applications of picryl chloride. Reagin was also elicited by another contact sensitizing agent, oxazolone. Some strain variation of the response to picryl chloride was found, with CBA mice being good responders and BALB/c and C57BL/10 mice being poor responders.


[The continuous graphic presentation of interdepartmental results (author's transl)]. The results of interdepartmental determinations can be clearly presented in the laboratory in two ways: 1. Entry on a test card, according to Shewhart, as used in internal quality control. 2. Entry on a test card, constructed on the principle of the Cusum test. By the latter procedure, systematic errors are detected sooner than with the usual test card. A graphic variant of the Cusum test is described; a V-mask is not required; the card superficially resembles the usual control card, and the calculation time is minimal. This method may also be used to advantage in internal quality control.


Determination of serum nucleotidase with cytidine monophosphate as substrate. Part II: Improvement of the procedure. Serum mucleotidase activity (EC 3.1.3.5) is measured by the amount of ammonia liberated from cytidine after incubation with cytidine deaminase (EC 3.5 4.5). Purification of the cytidine deaminase results in the abolition of interfering reactions, so that routine application is possible.


Isolation of rat transferrin using CNBr-activated sepharose 4B. 1. The isolation of transferrin from rat serum by means of affinity chromatography on CNBr-activated Sepharose 4 B is described. -2. Subfractionation by isoelectric focusing yielded two transferrin fractions with identical biological behaviour but with small differences in isoelectric point (6.0 and 5.8) and sialic acid contents.


An improved UV-spectrophotometric method for routine barbiturate monitoring. A simple, rapid, quantitative, low-cost UV-differential spectrophotometric method for the routine monitoring of phenobarbital in serum and cerebrospinal fluid is described. This method can also be used for monitoring methylphenobarbital (Phemiton) and primidone (Mysoline), since the major active metabolite of both drugs is phenobarbital. The basis for our procedure is Goldbaum's method (Anal. Chem., 24, 1604 (1952)). This method was improved with several modifications including a single extraction technique with dichloroethane, which has produced a very simple but still accurate method. The whole analysis takes less than 20 minutes. This procedure is accurate in the range from 1-100 mg/1 of phenobarbital in serum or cerebrospinal fluid.


Automation in the hematology laboratory. In the routine laboratory for hematology conflicting results may be obtained for the red blood cell parameters with the Coulter Counter Model S. These parameters2) are: mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH) and mean corpuscular hemoglobin concentration (MCHC). When the values of the MCHC are above 36 g/dl something must be wrong with the blood sample of the patient. One of the reasons can be agglutination e.g. by cold agglutinins. The blood sample should be reanalysed before and after heating for 1 hour at 37 degrees C. If the values change: cold agglutinins are present; if no change occurs paraproteins, or other disturbing factors, such as bilirubin or high leucocyte levels, will be found. MCH values may also be high in some cases e.g. if the red blood cells are coated with antibodies (Coombs test positive) or after ingestion of medicines like Azathioprine. These examples show that it is possible in some cases to correlate immunological findings with the red blood cell parameters. In addition to the results with the Coulter Counter Model S, some observations on the Hemalog (Technicon) are also presented.


[A routine method for thin layer chromatographic determination of urocanic acid in blood samples impregnated on filter paper cards (author's transl)]. A method is described for mass screening at birth for histidinaemia. Blood samples are collected on filter paper cards, as used in the Guthrie test. These samples are transferred, together with standards of histidine and urocanic acid, to thin layer chromatography plates by a type of sandwich technique. The plates can be evaluated semiquantitatively, after development and detection with Pauly's reagent. The detection limit for both substances is less than 10 mg/1 (60 mumol/1). Greater sensitivity and absence of interference, greatly reduce the proportion of equivocal results compared with the Guthrie test.


Metacontrol of hemispheric function in human split-brain patients. Four commissurotomy patients were tested for ability to match tachistoscopically presented stimuli with pictures in free vision, according to either structural appearance or functional/conceptual category. Patients were given ambiguous, structural, or functional instructions on any given run to trials with simultaneous double stimulus input to the two cerebral hemispheres. With ambiguous instructions, appearance and function matches were performed by the right and left hemispheres, respectively. When instructions were specific, appearance instructions tended to elicit appearance matches and right-hemisphere control. When function instructions were given, left-hemisphere control and function matches tended to be elicited. In three of the four patients, however, there was a significant number of dissociations between controlling hemisphere and strategy of matching.


Auditory evoked potentials during multichannel selective listening: role of pitch and localization cues. Auditory evoked potentials were recorded from subjects who listened selectively to tone pips arriving over one of three input channels. Their task was to detect occasional target tones of a slightly longer duration. In different runs the three channels were distinguished from one another by (a) pitch cues alone (800, 1,800, and 2,800 Hz), (b) localization cues alone (right ear, midline, ane left ear), and (c) both of these cues conjointly. In all three conditions the direction of attention was reflected in the amplitude of the N1 wave of the evoked potential, which was selectively enhanced to tones in the attended channel; tones in the central channels in the single-cue conditions, however, produced the least N1 lability and were the least discriminable. The N1 wave was interpreted as a sign of an initial stimulus set or filtering mode of selective attention, whereas a subsequent P3 wave was specifically associated with detections of the target stimuli.


Attention, practice, and semantic targets. Observers detected letters in streams of digits under conditions of divided or selective attention for a period of 10 hr. There were marked practice effects both on the detectability of targets and on the response criteria used by observers. The detectability of targets and the response criteria were both strongly dependent on events in the contralateral channel. The same effects were observed in a second experiment in which the task was to detect animal names in streams of nouns. The data are similar to those obtained in recent experiments using pure tones, so that a unified theory of attention should be possible, valid alike for semantic and nonsemantic messages. Such a theory is outline.


Perceiving and counting sounds.

Perceiving and counting sounds. Observers counted sequences of 20-msec tones that were presented to the same spatial location or alternated between spatial locations. Counting accuracy increased with increases in the silent interval between tones and increased at a faster rate when the tones were presented to the same location. In the second study, subjects monitored the same sequences of tones for a probe tone that was either higher or lower than the other tones. Probe recognition improved with increases in the silent interval between tones, and there was no significant decrement in monitoring tones alternated between spatial locations. In the next two studies, observers processed a sequence of tones presented at the same spatial location, but the tones could alternate in frequency by slightly more than an octave. Counting accuracy was poorer when the tones alternated in frequency. When subjects monitored these sequences of tones for the duration of a probe tone, recognition leveled off at a lower asymptote for sequences of tones alternating in frequency. The deficit in counting sounds alternating between spatial locations or frequencies appears to be due to a process that has difficulty integrating successive tones that are perceived at different spatial locations or pitch levels.


Choice between melodies differing in complexity under divided-attention conditions. The processing-capacity and arousal-level effect on choice between computer-generated "melodies" differing in complexity were compared in a divided-attention situation. Subjects were exposed to either aversive (97 dB, 350-Hz square wave) or mold (56 dB) auditory stimulation prior to blocks of trials involving choice between simple (4.00 bits/tone) and complex (9.17 bits/tone) melodies. Concurrently with the processing of the chosen melody on each trial, subjects either had no task at all or worked on one of four tasks that systematically differed in (a) the processing effort demanded, and (b) the likelihood of an arousal-level increase due to conceptual conflict and/or physical exertion. Measures were obtained of changes in choice and cardiac arousal due both to auditory stimulation and tasks. Results showed that the processing-capacity factors influenced choice quite independently of the arousal-level fluctuations due to tasks, and suggested that an arousal-level increase (due to stimulation), even when relevant for choice, may be mediated by a reduction in processing capacity.


Autonomic responses to shock-associated words in a nonattended message: a failure to replicate. Names of cities were shock associated and then embedded in material presented to the nonattended channel in a dichotic listening and shadowing situation. Despite earlier claims of differential responding to city names in the absence of awareness, no such differential responding was found. A test for conditioning following the dichotic listening task found that the subjects had been conditioned. Postexperimental interviews found that the subjects were aware of the city-shock contingency and had expected to be shocked during the dichotic listening task. Comparisons are made with other studies of galvanic skin responses to unattended words.


Flexible coding in word recognition.

Flexible coding in word recognition. An experiment was designed to examine the contribution of phonetic information in the processing of words in tachistoscopic recognition masking. Following stimulus presentation, subjects were required to indicate which of two alternatives had appeared. On trials containing word stimuli, the alternatives were either phonetically identical (SENT, CENT) or not (SOLD, COLD). Recognition performance was inferior in the former case, provided conditions were not structured to discourage reliance on phonetic information. The findings were interpreted as showing that more than one type of coding process can underly the word superiority effect. Phonetic information is ordinarily used to code words in this type of task, but an alternative processing tactic (e.g., one relying on visual or perhaps semantic codes) can also be effectively used in word recognition when phonetic information does not discriminate well among response alternatives.


Why a Y is not a V: a new look at the distinctive features of letters. Although a feature detection theory of pattern recognition is consistent with many recent physiological and psychological findings, the specific rules governing the perception of the distinctive features of letters have not yet been determined. This article presente two new experimental procedures for determining these rules. Both procedures are demonstrated by the investigation of the specific rule involved in the perception of the letter attribute leg which distinguishes Y from V, F from C, and H from U. Whereas previous methods investigating the distinctive features of letters have focused primarily on archetypal letter forms, the present methods are based upon an investigation of ambiguous characters, those characters which can be assigned either of two letter labels with equal probability. One of these procedures allows for the investigation of these rules without the influence of external context, whereas the other allows for an investigation of the particular effects that external context can have on these rules.


Early versus late stages of processing and their relation to functional hemispheric asymmetries in face recognition. To determine whether perceptual asymmetries for faces occur at early or late stages of stimulus analysis, subjects compared the members of a pair of faces which appeared in the right or left visual field, either to each other or to a previously presented sample. The first two experiments established that manual reaction times were consistently shorter to left-field presentation only when test faces were compared for identity to a memorized sample (Experiment 2), but not when they were compared to each other (Experiment 1). By varying the interstimulus interval between the sample and test (Experiment 3), it was found that a consistent left-field superiority was absent for at least the first 50 msec following sample offset, suggesting that during that time both hemispheres have access to a short-lived, visual trace that represents the results of the early, precategorical processing stages. Beyond 100 msec, or earlier if the trace is degraded by a masking field (Experiment 4), a left-field advantage is observed. Experiment 5 showed that higher order comparisons between photographs and caricatures yield a left-field superiority even in a memory-free situation. Together, the results indicate only higher order processes, such as are needed to maintain a relatively permanent memory representation or to compare caricatures with photographs, require the specialized functions peculiar to the right hemisphere. Lower-order, precategorical processes seem to be common to both hemispheres.


Effect of identity in the multiletter matching task. This study was concerned with the nature of the character-comparison process involved in same-different judgments of arrays of letters. One condition replicated the standard matching task, with subjects pressing one key to indicate that the two arrays of letters were identical in all positions, and another key to indicate difference in one or more positions. A second condition reversed the standard decision rule and required the subjects to distinguish between arrays that differed in every position from those that matched in one or more positions. Reaction times were shorter to identical arrays in both conditions, indicating that identity effects observed in this and previous studies must be attributed to identity per se and not to decision or response factors. Mathematical analysis of the data revealed that, although a serial self-terminating model could be modified to give a good description of processing in this task, a model based on parallel processing was able to provide a better account both quantitatively and qualitatively. The analysis also indicated that subjects reduced their average reaction times by terminating the comparison process prematurely on some trials, and this guessing strategy was shown to have important implications for the shapes of the reaction time functions observed in this task.


Testing the role of vertical symmetry in letter matching. A series of experiments tested a recent suggestion that vertical symmetry of a stimulus display can serve as a visual diagnostic for responding "same" in a letter-matching task. The data of chief interest were same reaction times to vertically symmetric (e.g., AA) and asymmetric (e.g., LL) displays, each composed of two side-by-side uppercase letters. Overall, the data argue against subjects' use of vertical symmetry as a diagnostic in dealing with letter pairs. The results were interpreted within the context of recent work on symmetry. In particular, it was suggested that the importance of structural diagnostics in a matching task may be inversely related to the codability of the stimulus elements being compared.


The perception of egomotion.

The perception of egomotion. Egomotion is defined as any environmental displacement of the observer. Twenty stationary observers viewed computer-generated films that simulated rectilinear egomotion of constant speed and altitude over an endless plain. The heading point could be 0 degrees, 15 degrees, 30 degrees, 45 degrees, 60 degrees, 75 degrees, or 90 degrees to an observer's right of the screen center. The screen was 53 degrees wide. Hence, there was a constant heading toward a point on the horizon, but the heading point was not always in view. The typical observer's mean pointing bias was 5.56 degrees to his right and his SD pointing error was 5.18 degrees. The results indicate that these abstract view samples of a pure egomotion ambient optic array are equally effective in giving rise to a compelling perception of egomotion. The results also indicate that observers can perceive the direction of their heading whether or not the heading point is in the view, although accuracy did vary slightly with the specific view. A pointing control using linear perspective scenes whose vanishing points fell off-view showed the same pattern of pointing errors with an overall rightward pointing bias of 3.19 degrees and with an SD pointing error of 3.04 degrees.


A study of thyroid disease in family practice. Thyroid disease is relatively common in family practice, yet is often undiagnosed or poorly managed. This study examines several aspects of thyroid disease in a large, semirural family practice setting and exemplifies the type of practical clinical research that can be done in family medicine. An overall prevalence of approximately one percent was determined for thyroid disease in this practice. In a series of 85 patients, the ratio of hypothyroidism:hyperthyroidism:euthyroid goiter was 9:2:1 respectively. Initial signs and symptoms recorded for these patients conformed closely to the findings in other large series. Eighty percent of the patients with idiopathic hypothyroidism never had enlarged glands, whereas 100 percent of the patients with hypothyroidism associated with Hashimoto's thyroiditis had enlarged glands. Laboratory aids such as serum thyroid stimulating hormone (TSH), anti-thyroid antibodies, and radioactive iodine uptake (RAIU) and scans were inadequately utilized. Medical and/or surgical consultation was obtained in 17.5 percent of patients with hypothyroidism, 80 percent of patients with hyperthyroidism, and 63 percent of those with euthyroid goiter. Currently 95 percent of the hypothyroid patients and 100 percent of the hyperthyroid patients are euthyroid.


Primary hyperparathyroidism in the primary care setting. A series of 36 patients with surgically proved primary hyperparathyroidism is reported. From this group a clinical profile consisting of obesity, anxiety, and/or depression in a mildly hypertensive, middleaged female was derived. Women constituted 92 percent of the patients. The serum calcium was confirmed again as the single most valuable test in the evaluation of this disorder.


The post-suicide family and the family physician. It is estimated that there are 750,000 people each year who are intimately affected by suicide. Prominent among these are the family survivors and their family physician. This paper offers a time frame which divides the period following the suicide into three phases: Immediate (the first ten days after the suicide); Intermediate (after the first ten days through the first year); and Extended (from the first year until restitution occurs). It identifies the chief emotional reactions which occur in each phase, explores their psychodynamic origins, and proposes suggestions for appropriate management during each of the three periods. The goal of this plan of management is to enable the family physician to function in a supportive emphatic, and restorative manner for the post-suicide family.


Doctor-patient communications in a private family practice. One hundred fifty-five randomly selected patients in a private family physician's office were interviewed immediately before and immediately after their visit with the doctor in an attempt to assess the degree of misunderstanding that occurs in doctor-patient communications. Fifty-four percent of these patients either forgot to mention all their medical problems to the physician or they confused or forgot certain instructions concerning their diagnosis or treatment. A X2 analysis failed to reveal any significant sex or age differences in the proportions of misunderstandings. There was also no correlation between the number of misunderstandings, the amount of time the doctor spent with the patients, the patient's rating of their own health on a scale of one to ten, and the patients' complaints or praises about their medical treatment. The number of years of formal education completed by the patient showed a direct relationship to the number of misunderstandings. Patients on their first three visits to this office  tended to misunderstand more of their medical instructions. Furthermore, the study suggested that patients with chronic internal diseases and those who express excessive trust in their physician might have an increased proportion of misunderstandings.


The Adlerian approach: a practical psychology for family practice. A systematic approach to understanding the patient's personality and helping him cope with common life problems is found in Adlerian Psychology. It is uniquely appropriate to family practice because it stresses the interpersonal purposes of behavior and symptoms and the influence of family constellation on the development of the individual life-style. By obtaining a small amount of data about the patient's present life situation and his family of origin, the physician can gain a basis for understanding how the patient developed his unique way of acting and reacting to the physical and social stresses of life. Interpretation of two or three early recollections reveals what the patient expects of himself, others, and life. The insight thus gained is used as the basis for a holistic assessment of the problem; a directive, supportive, action-oriented plan for treatment; and an ongoing doctor-patient relationship of mutual respect.


Describing learning experiences of undergraduate medical students in rural settings. This article describes a method for evaluating clinical experiences gained by undergraduate medical students at the University of Washington who take a family medicine clerkship at one of five rural communities. The student's clinical, community and practice management activities are documented on a standardized daily log. This log permits efficient transcription to punch cards. Data analysis results in a list of diagnoses, procedures, and community and practice management activities. These experiences are presented in order of frequency with a distribution of experiences by level of student responsibility, by location or agency, and by follow-up versus first contact. The results presented here constitute a summary profile over three academic quarters. The data reveal a substantial student exposure to medical problems common in family practice. Students assume a relatively high level of responsibility and experience continuity in patient care. This paper describes various ways in which these results are used.


Elective experiences in family medicine for medical students. The place of elective experiences in the predoctoral educational program of the Department of Family and Community Medicine of the College of Medicine of The Pennsylvania State University is described. General educational objectives and brief descriptions of courses are presented, and the educational approach is discussed. An overview of the comprehensive educational program is provided, including the methods used and relationship to the total medical school curriculum.


The relation between physician and patient age in family practice. A study of 100 selected Wisconsin family physicians demonstrated that younger physicians generally had more contact with younger patients, middle-aged physicians had an even distribution of patient age contacts, and older physicians had more contact with older patients. The increase in older patients became pronounced for 56 to 60-year-old physicians. Generally a ten-year increase in physician age was accompanied by a five-year increase in patient age. The rising average age of the American population, combined with the direct physician-patient age relationship demonstrated here suggest that geriatrics will become increasingly relevant not only in the continuum of medical education but also for the individual practicing physician.


Alopecia: a systematic appraoch to diagnosis and therapy. Alopecia is a difficult problem for the physician. It is a common reason for specialist referral because of frustration with the complexities of etiology, the impatience of the patient, and often some uneasiness of diagnosis in the mind of the physician. The concern for possible serious underlying causes, and the relative expense required to rule these out also play an important role in the early referral of these cases. The vast majority of these cases do not reflect serious disease and so do not require expensive work-ups. Trhough a systematized approach, they can be easily taken care of by the patient's primary physician. This paper presents a practical approach for the busy physician to deal with this problem quickly and easily in a systematic manner that minimizes the possibility of overlooking serious problems and defines the level of investigation necessary in most cases.


Phase shifting the circadian rhythm of neuronal activity in the isolated Aplysia eye with puromycin and cycloheximide. Electrophysiological and biochemical studies. The effects of pulse application of puromycin (PURO) or cycloheximide (CHX) were tested on the circadian rhythm (CR) of spontaneous compound action potential (CAP) activity in the isolated Aplysia eye. CAP activity was recorded from the optic nerve in constant darkness at 15degreesC. PURO pulses (6, 12 h; 12--134 mug/ml) and CHX pulses (12 h, 500--2,000 mug/ml) caused dose-dependent phase delays in the CR when administered during projected night. PURO pulses (6 h, 125 mug/ml) caused phase advances when given during projected day and caused phase delays when given during projected night. In biochemical experiments PURO (12 h, 20 mug/ml) and CHX (12 h, 500 mug/ml) inhibited leucine incorporation into the eye by about 50%. PURO (12 h; 50, 125 mug/ml) also changed the molecular weight distribution of proteins synthesized by the eye during the pulse. The effect of PURO (12 h, 125 mug/ml) on the level of incorporation was almost completely reversible within the next 12 h but the phase-shifted eye showed an latered spectrum of proteins for up to 28 h after the pulse. In electrophysiological experiments spontaneous CAP activity and responses to light were measured before, during, and after drug treatments. In all, eight parameters in three periods were analyzed quantitatively. Of these 24 indices, only 3 showed significant changes. PURO increased spontaneous CAP frequency by 67% 0-7 h after the drug pulse and increased the CAP amplitude of the tonic light response by 23% greater than 7 h after the pulse. CHX increased the intraburst spontaneous CAP frequency by 33% during the pulse and CAP frequency of the tonic light response by 32% 0-7 h after the pulse. The above data indicate that phase-shifting doses of PURO and CHX inhibit protein synthesis in the eye without causing adverse electrophysiological effects, and suggest that protein synthesis is involved in the production of the CR of the isolated Aplysia eye.


Release of proteins from the inner surface of squid axon membrane labeled with tritiated N-ethylmaleimide. Proteins in the inner surface of the squid axon membrane were labeled by intracellular perfusion of [3H]N-ethylmaleimide (NEM), which forms covalent bonds with free sulfhydryl groups. The excitability of the axon was unaffected by the [3H]NEM perfusion. After washout of the unbound label, the perfusate was monitored for the release of labeled proteins. Labeled proteins were released from the inner membrane surface by potassium depolarization of the axon only in the presence of external calcium ions. Replacement of the fluoride ion in the perfusion medium by various anions also caused labeled protein release. The order of effectiveness was SCN- greater than Br- greater than Cl- greater than F-. The extent of labeled protein release by the various anions was correlated with their effects on axonal excitability. The significance of these results is discussed.


Potassium current kinetics in Myxicola axons. Effects of conditioning prepulses. In Myxicola giant axons the time constants for activation of the potassium conductance (GK) after prepulses less depolarized than a test pulse are comparable to the time constants for turn off of GK after prepulses more depolarized than the same test pulse. The absolute magnitude of the steady-state level of GK is also independent of prepulse amplitude in Myxicola. The results are contrasted with recent observations on voltage-clamped frog nodes.