Quantitative histological studies on the lateral geniculate nucleus in the cat. III. Distribution of different types of neurons in the several layers of LGN. An attempt is made on the definition of proportional distribution of the different types of neurons in the layers of LGN by means of quantitative method. On the basis of nuclear volume, nuclear and cell diameters the different types of neurons were separated according to their size and shape. The ratio of relay and interneurons proved to be 2:1 in all layers of LGN of cat. The proportional distribution of further subgroups of neurons was also defined. The bilateral connections between the relay and interneurons based on initial axon collateral of TCR neurons and on axon terminals and dendritic appendages of INs, are also calculated. The interneurons--in the LGN--have widespread contacts with both types of relay neurons, similarly the relay neurons contact the interneurons. The numerical data of morphological observations are accord with the results of physiologists.


[Cervical coagulation (author's transl)]. Coagulation of the cervix is one of the most frequently carried out gynaecological procedures. All the same, protagonists and antagonists produce numerous arguments about the indications for the operation, the best techniques to adopt and whether it does have any prophylactic action against cancer. The author, in this article, which reviews the arguments and counter-arguments, summarises the opinion of several specialists about this matter. The advice given seems to be very divided as far as the indications are concerned, the author himself reserving coagulation especially for those cervices from which pathological discharges emanate, after he has controlled the state by smears and colposcopy, and has considered atypical epithelia as a contra-indication to coagulation. The variety of techniques in use prove that the problem has not been resolved. To bipolar diathermy coagulation has followed cryosurgery and coagulation at 90 degrees C. Finally, the prophylactic role against cancer is discussed. Whatever the attitude taken, coagulation of the cervix does not mean that follow-up may be dispensed with.


Pricing health services: verification of a monopoly pricing model for dentistry. A model of monopoly with constant marginal costs is used to derive a price function for dental services. The implications of the model are tested using data on individual practitioners from a national survey. The implications of the model are met by the data, providing strong evidence of the appropriateness of the monopoly model to analyses of the market for dental services. The empirical evidence also provides substantial information on the determinants of dental fees.


Qa-2 and Qa-3 antigens on lymphocyte subpopulations. I. Mitogen responsiveness. The effects of anti-Qa-2 plus C and anti-Qa-3 plus C on mitogen-induced proliferation were studied. Both of these antisera in the presence of C markedly reduced both Con A- and PHA-induced proliferation while having little or no effect on LPS-induced proliferation. LPS, Con A, and PHA cultures and cultures containing media alone, examined at 72 hr, contained high proportions of Qa-2+ and Qa-3+ cells.


p30-Anti-p30 immune complexes: intravascular clearance and extravascular sequestration in rats bearing Moloney sarcoma. Complexes of 125I p30, a viral core polypeptide, and rat anti-p30 antibody, preformed in vitro, were injected into the heart of BN rats bearing Moloney sarcomas (MST) and of BN rats bearing an unrelated tumor or unexposed to tumor. Complexes were cleared from the circulation of MST-bearing rats more rapidly than from sera of controls and were almost completely eliminated after 30 hr. There was no relationship between rate of disappearance and size of tumor or levels of circulating complexes. Disappearance rates in rats with progressing and regressing tumors were similar. Uncomplexed labeled p30 was cleared from the circulation of tumor-bearing and control rats with kinetics similar to those of labeled complexes. Complexes were localized in the spleen of tumor-bearing and control rats, but much more in spleens of MST-bearing rats. No other tissues, including tumor, concentrated complexes, nor was there binding to peripheral blood and spleen cells. The data suggest that augmented clearance and sequestration were due to the formation of large insoluble complexes that were rapidly removed by the reticulo-endothelial system.


Regulation of alloantigen-induced cytotoxic responses by concanavalin A-activated lymphoid cells: suppression by antigen elimination. Spleen cells activated by concanavalin A (Con A) and subsequently irradiated with 1500 R were able to suppress the primary in vitro cytotoxic lymphocyte (CL) response of syngeneic splenocytes to H-2 disparate targets. Similarly activated and irradiated BALB/c (H-2d) splenocytes which were cultured with C57BL/6 (H-2b) stimulators for 24 hr developed cytotoxicity for H-2b, but not H-2d, tumor cell targets. This suggested that Con A-activated cells allogeneic to the stimulator might suppress the development of cytotoxic lymphocytes by eliminating antigen early in mixed leukocytes culture. This hypothesis was supported by the observation that suppression of primary cytotoxic responses was overridden by the use of greater numbers of stimulator cells. Moreover, Con A-activated (A X B)F1 lymphocytes suppressed the response of parent A to the H-2 disparate strain C to a much greater extent than they suppressed A-anti-B responses generated in such cultures. Addition of greater numbers of F1 suppressor cells did reveal a suppressive effect not readily explicable on a cytotoxic mechanism, in that modest but significant suppression of the A-anti-B response was observed. Thus, antigen elimination is a major, but not exclusive, mechanism in the suppression of CL responses by Con A-activated cells.


The effects of passive immunization with tumor-specific antiserum on the active immune response of mice to sublines of leukemia L1210. In vivo, tumor cell killing was monitored with 131I-IUdR-labeled tumor cells and whole-body measurement of retained radioactivity. Treatment with antiserum in quantities that were not sufficient to kill the total leukemia cell inoculum (i.e., antigen excess) caused an immunopotentiation of the active immune responses; this was manifested by an accelerated rate of tumor cell killing beginning between days 10 and 11. The results obtained in vivo were confirmed by in vitro quantitation; both the cytotoxic antibody and cell-mediated immune responses were potentiated by the injection of antiserum. Immunosuppression was also observed in passively immunized mice. Whether potentiation or suppression occurred was dependent on the relative amounts of antiserum and leukemic cells injected and the innate immunogenicity (and/or antigenicity) of the leukemic cells; antibody excess and high immunogenicity favored suppression.


Cell-mediated destruction of cells grown on artificial capillaries. This investigation was designed to determine the conditions required to assess cell-mediated destruction of target L-cells grown on artificial capillaries. In control cultures that contained L-cells alone, solid nodules with a diameter of 1 mm as well as dense cellular growth could be visually observed by the 12th day of culture. Alloimmune spleen cells from both immunized and normal C57BL/10 mice were shown to be capable of destroying tritiated thymidine-labeled L-cells growing on artificial capillaries. The destruction of target cells grown as monolayers in capillary culture correlated well with monolayer cultures incubated in 16-mm plastic tissue culture wells. When target cells were grown in capillary culture for 5 days before the addition of effector cells, significant destruction by normal effector cells was not observed until the 15th day of culture whereas that mediated by immune cells was observed by the 7th day. The possible effects of cell-culturing conditions on the kinetics of cell-mediated destruction in capillary chambers are discussed.


Suppression of growth of guinea pig line-10 hepatocarcinoma. II. Effect of passive transfer of xenogeneic and syngeneic antibodies and normal lymphoid cells. Complete or partial protection against the line-10 hepatocarcinoma was conferred to a significant number of strain-2 guinea pigs by the passive transfer of antibodies reactive to antigens from line-10 cells. Immunoglobulins were administered intradermally and injected sites were subsequently challenged with line-10 cells. Immunoglobulins prepared from the sera of rabbits that had been immunized to line-10 cells and from the sera of guinea pigs that had been rendered immune to this tumor by previously described methods were more effective than immunoglobulins obtained from normal rabbit or guinea pig sera. Protection was abolished if immunoglobulins were absorbed with line-10 cells. Antitumor effects were dependent on the close contact of antibodies and tumor cells. Protection was greater if normal syngeneic peritoneal exudate cells were transferred in addition to the immunoglobulins. A possible mechanism for the antitumor effects observed is that of antibody-dependent cellular cytotoxicity.


Plasmacytomas of the NZB mouse.

Plasmacytomas of the NZB mouse. Plasmacytomas were readily induced in NZB mice by three i.p. inoculations with pristane (2, 6, 10, 14-tetramethylpentadecane). In comparison with comparable induction regimens in BALB/c mice a) the latent period for plasmacytoma development was significantly longer in NZB's; b) the frequency of IgA paraproteins produced by NZB tumors was much reduced and that of IgG (IgG1, IgG2a, IgG2b, IgG3Y was significantly increased; and c) the frequency of carbohydrate-binding paraproteins was 10-fold lower. There was a high frequency of primary ascites containing more than one paraprotein, but none of 25 such tumors produced more than one immunoglobulin class on serial transplantation.


Membrane proteins of the P388D1 macrophage cell line: isolation of membrane polypeptides that bind to the Fc portion of aggregated IgG. Lactoperoxidase-catalyzed cell surface radioiodination was employed to radiolabel membrane polypeptides of a murine macrophage cell line P388D1. Optimal conditions for radioiodination of P388D1 cells were determined and were found to differ from conditions used to label lymphoid cells. SDS-polyacrylamide gel electrophoresis of detergent soluble membrane polypeptides revealed that 9 to 10 molecular species from 1 X 10(5) to 0.15 X 10(5) daltons were labeled. Radioiodinated, Triton X-100 extracted P388D1 membrane polypeptides were subjected to affinity chromatography on aggregated IgG:Sepharose columns. Elution of the bound polypeptides and analysis by SDS-polyacrylamide gel electrophoresis revealed polypeptides with an apparent molecular size of 8 X 10(4), which possess binding affinity for the Fc portion of aggregated IgG. The 8 X 10(4) dalton membrane polypeptides do not readily aggregate, are resistant to degradation, are not composed of disulfide-linked subunits, and do not appear to contain much carbohydrate. Cellular binding characteristics paralleled the binding of soluble receptor for sieved fractions of aggregated IgG suggesting that these polypeptides may be responsible for the in situ binding of aggregated IgG to P388D1 cells.


Studies on immunosuppression by cobra venom factor. II. On responses to DNP-Ficoll and DNP-Polyacrylamide. We have reassessed the effects of CVF administration on the humoral responses to two T-independent immunogens: DNP-Ficoll and DNP-Polyacrylamide. With high immunogen doses, little or no evidence of suppression was found. However, when the immunizing dose was reduced, suppression of both IgG and IgM responses became apparent. As indicated in a previous report, the immunosuppressive effect of CVF on T-dependent responses may result not only from C depletion but also from the generation of C cleavage products that may impair the auxiliary contribution of macrophages to the generation of these humoral responses. A similar mechanism may be applicable to the suppression of antibody production to DNP-Ficoll and DNP-PAA in view of recent reports showing a macrophage requirement for the response to these immunogens.


Studies on immunosuppression by cobra venom factor. III. On early responses to sheep erythrocytes in C5-deficient mice. CVF administered before immunization can profoundly depress humoral responses in C-sufficient mice. In AKR/JC5- mice given CVF before i.v. immunization with SRBC, only IgG levels were depressed, IgM titers being equivalent to those of untreated controls. The immunosuppressive effect became inapparent when the i.p. route of immunization was adopted. In DBA/2J C5- mice reduction of both IgG and IgM titers was observed irrespective of the route of immunization. The degree of suppression was, however, much more marked when mice were challenged intravenously. Essentially identical results were obtained with C5+ DBA/1J mice. These studies indicate that immunosuppression by CVF is unrelated to activation of the late C components. The significance of these findings is discussed with reference to the possibility that the generation of biologically active C fragments in conjunction with a C3 deficiency may account for immunosuppression by CVF.


Transplantable IgD immunoglobulin-secreting tumors in rat. The LOU/C/Wsl rat inbred strain presents a high incidence of spontaneous malignant ileocecal immunocytomas or monoclonal immunoglobulin-secreting tumors. Some tumors have been transplanted in histocompatible animals over years without any change in their secretion products. Among approximately 600 different monoclonal proteins we have studied so far, we recognized six showing properties different from those of rat IgM, IgA, IgE, or IgG classes, and characteristic of the IgD class.


A method for measuring desquamation and its use for assessing the effects of some common exfoliants. Desquamation has been measured in the past by a counting chamber technique after corneocytes are removed from the skin surface and disaggregated in a dilute surfactant solution. However, we have found that complete corneocyte disaggregation is not always possible when these aggregates are recovered from sites where patent peeling is induced. Corneocyte counting in such instances is difficult or impossible. We have devised a method of measuring desquamation wherein the desquamating cells are determined as the total alkali-soluble protein after they are removed from the skin surface with an inert, self-hardening gel. Highly reproducible desquamation rates are obtained, characteristic of the individual subject. Using some common exfoliants, we show that pharmacologic response, observed as an increase in desquamation rate, is also an individual characteristic.


Effect of occlusion on Trichophyton mentagrophytes infections in guinea pigs. The effect of occlusion and griseofulvin on the duration and severity of acute dermatophytosis was assessed in guinea pigs. Sixty guinea pigs given standard Trichophyton mentagrophytes infections were divided into 5 groups: (A) control, (B) intermittent wet occlusion, (C) continuous-wet occlusion, (D) griseofulvin, (E) griseofulvin-continuous-wet occlusion. Lesions were largest in the control group, smallest in the griseofulvin-continuous-occlusion group, and of intermediate area in the other groups. The degree of inflammation and alopecia was not affected by occlusion, but was markedly reduced or eliminated with griseofulvin. Healing of the lesions occurred more rapidly in the griseofulvin-continuous-occlusion group than in any other group. This study suggests that either occlusion of the inoculated site or oral griseofulvin markedly reduces the expected area of the fungal lesion, and occlusion together with griseofulvin shortens the duration of the lesion.


Photoinactivation of cultured skin fibroblasts by sublethal doses of 8-methoxypsoralen and long wave ultraviolet light. Cultured guinea pig skin fibroblasts were treated with 8-methoxypsoralen (8-MOP) and UVA light. Determination of 3H-TdR-uptake as well as counting of the number of adherent cells was carried out 24 hr later. Incubation of fibroblasts with varying concentrations of 8-MOP (10(-4) to 10 microgram/ml) or 1 to 5 J/cm2 UVA alone showed no effect. When 8-MOP-photosensitization was followed by UVA a dose response was observed. This ranged over 3 orders of magnitude of the concentration of 8-MOP. Changes in irradiation energy produced a higher inhibition of 3H-TdR incorporation as compared to changes in 8-MOP concentrations. Using the same energy of UVA changes in which 3H-TdR uptake was inhibited by 50% showed no loss of plating activity. A fraction of these cells underwent DNA synthesis and division after reseeding. The results indicate that under the dose regimens currently used for the treatment of various skin  disorders a proportion of the cells may become sublethally photoinactivated to undergo division. When reseeded these cells still are able to perform cellular functions such as spreading and attachment.


Suppression of sebaceous gland development in laboratory animals by 17alpha-propyltestosterone. Topical application of the testosterone derivative 17alpha-propylandrost-4-en-17beta-ol-3-one (Win 17665) caused a dose-related regression of the hamster flank organ and guinea pig supracaudal gland in mature male animals. Histological examination confirmed that this action of Win 17665 was on the size of the hamster sebaceous glands and was reversible on cessation of treatment. Topical application of Win 17665 also counteracted flank organ stimulation by directly applied 5-alpha-dihydrotestosterone and 4-androstene-3,17-dione. Seminal vesicle weight was reduced after the repeated subcutaneous administration of 100 mg/kg of Win 17665 but not after repeated oral administration of 320 mg/kg or topical administration of 1 gm/kg of Win 17665.


Ultrastructural study of the nuclei in premitotic and repair DNA synthesis following UVB injury. Ultrastructural changes in nuclei synthesizing DNA were studied by cytochemical technique. Guninea pigs ears were UVB irradiated and TdR-H3 was injected intradermally into the irradiated sites 1 hr before biopsy. Areas of the epidermis containing more than 80% of cells in DNA (repair or premitotic) synthesis identified by light microscopic autoradiography were selected and cut at  600 A. The glycolmethacrylate sections were stained with uranyl acetate and lead citrate, and consecutive sections were incubated with 0.01% pronase and 0.5% RNase before staining in order to observe DNA. In cells undergoing DNA repair, the zone of DNA became discontinuous and DNA was scattered throughout the entire karyoplasm as small aggregates and fine filaments. Nuclei in S-phase showed essentially the same change, but quantitatively the disappearance of DNA from the nuclear membrane and distribution in the karyoplasm became much greater. These changes were not seen in specimens treated without cytochemical technique.


A controlled investigation of the pharmacokinetics of gentamicin and tobramycin in obese subjects. For determination of the best basis on which to calculate dosages of gentamicin or tobramycin to be administered to obese patients, the pharmacokinetics of these drugs were studied in 13 obese subjects and 13 subjects of a normal weight following intravenous infusion of 1 mg/kg. Half-lives, elimination constants, and absolute and relative volumes of distribution were calculated. Concentrations of drug in serum were significantly higher and relative volumes of distribution were significantly lower in obese subjects as compared with controls. However, relative volumes of distribution based on lean body mass of obese subjects were significantly greater than those of normal-weight subjects. These results indicate that gentamicin and tobramycin are distributed less to adipose tissue than to other tissues, but partial distribution to adipose tissue does occur. The mean relative volume of distribution in obese subjects closely approximated that in normal subjects when normalized body mass plus 40% of the adipose mass was used as the total weight in obese subjects.


Duration of hospitalization for acute bacterial empyema at Boston City Hospital during 12 selected years from 1935 to 1972. The duration of hospitalization for acute bacterial empyema of the pleura was determined for all cases at Boston City Hospital during 12 selected years between 1935 and 1972. Patients whose infection was acquired after admission stayed in the hospital longer than those in whom the empyema, or the infection of which the empyema was a complication, was present at the time of admission. The differences were mostly related to serious underlying disease in the hospital-acquired cases. However, the duration of hospitalization after the empyema was bacteriologically confirmed was not much different in the community-acquired and hospital-acquired cases. Hospital stay was further prolonged in patients whose empyema was superinfected with new bacterial species after the original infecting organisms were determined. Hospitalization was shorter in the 10 selected years between 1974 and 1972, when penicillin and other active antibiotics were used, than in two years before penicillin became available, 1935 and 1941.


Comparative nephrotoxicity of aminoglycoside antibiotics in rats. Netilmicin, gentamicin, tobramycin, amikacin, kanamycin, streptomycin, and sisomicin were given daily for 15 days to groups of rats at three dosage levels corresponding to 10, 15, or 25 times the dose recommended for humans on a weight basis. Decreased urinary osmolality and increased urinary excretion of protein and beta-N-acetyl hexosaminidase were dose-related features of nephrotoxicity. Decreased tubular resorption of glucose and phosphate were observed with the most toxic regimens after extensive renal damage had occurred. All aminoglycosides accumulated in renal tissue; however, the concentration of drug in the renal cortex at the time the rats were killed was not useful for the prediction of renal impairment. Streptomycin and netilmicin exhibited a flat dose-reponse curve with respect to histological damage, as compared with the curves for the other drugs. Results of studies of creatinine clearance and examination of renal tissue suggested the following order of increasing toxicity of the treatment regimens: (1) 0.9% NaCl and uninjected controls; (2) streptomycin; (3) netilmicin; (4) tobramycin; (5) sisomicin, amikacin, and kanamycin; and (6) gentamicin.


Reactogenicity and immunogenicity of whole and ether-Tween-split influenza A virus vaccines in volunteers. Two separate, double-blind studies were carried out in volunteers to compare the reactogenicity of, and serum antibody responses to, whole or ether-Tween-split inactivated influenza virus vaccines. In both studies the ether-Tween-split vaccines induced a lower rate of reactions. The serum hemagglutination-inhibiting (HAI) antibody response of volunteers to the A/Scotland/74 component of the split vaccine used in the first study was significantly greater than that following inoculation of A/Scotland/74 whole-virus vaccine. The neuraminidase-inhibiting (NI) antibody responses of the volunteers to each vaccine were similar. In the second study, a markedly better NI antibody response to the influenza A virus component was seen following immunization with split-virus vaccine, but the HAI antibody response to both split and whole vaccines was the same. In both studies the serum HAI antibody responses to the B/Hong Kong/73 component of the vaccines were similar. Challenge of the volunteers with attenuated influenza viruses homologous to the influenza A component of the vaccines showed both types of vaccines to be protective.


Cell-mediated immune response to liver tissue antigen and hepatitis B surface antigen after infection with hepatitis B virus in humans. The in vitro correlates of cell-mediated immunity to liver tissue antigens and hepatitis B surface antigen (HBsAg) were studied in groups of subjects with acute and chronic hepatitis B virus (HBV) infection and in a population of HBV-seronegative controls. The technique of in vitro lymphocyte transformation (LTF) was employed in these studies. No LTF response to liver-specific antigen and HBsAg was observed in the control population. LTF activity in response to HBsAg was present in 11 of the 14 subjects with acute type B viral hepatitis during the early phase of the disease, and eight of these subjects also had LTF reactivity to liver antigen. During the convalescent phase the LTF reactivity to these antigens usually disappeared. More than 70% of patients with chronic carriage of HBsAg who had elevated levels of liver enzymes showed LTF responses to HBsAg, and a significant number of these subjects also exhibited LTF response to liver-specific antigen. On the other hand, chronic HBsAg carriers who persistently showed normal liver enzyme values (asymptomatic carriers) failed to show significant responses to liver antigen or HBsAg. It is suggested that the persistence of cellular reactivity to liver antigens may lead to the establishment of chronic liver disease.


Antigenic drift and efficacy of influenza virus vaccines, 1976--1977. A unique opportunity occurred in February 1977 to assess the efficacy of an influenza virus vaccine given to military personnel in doses of 400 chick cell-agglutinating (CCA) units of A/Victoria/3/75, 400 CCA units of A/New Jersey/76, and 500 CCA units of B/Hong Kong/72 viruses. After cessation of all influenza virus vaccine administration in mid-December 1976, approximately 200 unvaccinated U.S. Air Force personnel arrived per week beginning February 1, 1977, at Lowry Air Force Base, Denver, Colorado. Arriving unvaccinated personnel were assigned to one of 12 units with previously vaccinated personnel. A sharp outbreak of influenza A occurred on the base during February that was due to an A/Texas/1/77-like virus, a variant of the A/Victoria/3/75 prototpye. Fifty-four cases of influenza A were documented in the student population on the base. During the two-week peak of the outbreak, attack rates were 10-fold higher in unvaccinated than in vaccinated students, and the overall estimate of vaccine efficacy was 80%. Thus, despite animal tests suggesting considerable antigenic drift, a vaccine containing influenza A/Victoria/3/75 virus provided good protection against the variant strain.


Behavior of respiratory syncytial virus in piglet tracheal organ culture. Piglet tracheal organ cultures were infected with respiratory syncytial virus (RSV) and observed for 21 days. Light and immunofluorescence microscopy demonstrated destruction of the ciliated epithelial cells and the presence of viral antigens in the epithelium. Virus was shed in high titer for 12--19 days. Ciliostasis could be quantitated, and it was shown that several strains of RSV grew and damaged tracheal organ cultures in a similar fashion. A temperature-sensitive mutant of RSV, ts-1, was examined at permissive (33 C) and restrictive (37 C) temperatures. This mutant, although somewhat attenuated at 37 C, was still found to cause damage to the ciliated epithelium and to replicate at both temperatures. THIS BEHAVIOR IS SIMILAR TO THAT AFTER INOCULATION OF TS-1 INTO VOLUNTEERS. This in vitro model may prove useful in the study of RSV disease and in the evaluation of candidate live virus vaccines.


Prediction of efficacy of antimicrobial agents in treatment of infections due to Chlamydia trachomatis. Although Chlamydia trachomatis is readily eradicated by systemic therapy in patients with acute urethritis, systemic therapy is less satisfactory in treatment of chronic trachoma. The activities of antimicrobial agents against C. trachomatis in cell cultures when the antimicrobial agents are added 1 hr after the C. trachomatis (minimal inhibitory concentration [MIC]) predicts efficacy of the drugs in the treatment of urethritis but does not necessarily predict efficacy in the treatment of chronic ocular trachoma. Concentrations of antimicrobial agents required to eradicate C. trachomatis when the agents were added 48 hr after inoculation of the cell cultures with C. trachomatis exceeded the MIC by several logarithms, and minocycline, doxycycline, and rifampin were markedly more active than tetracycline, erythromycin, or several other antimicrobial agents. Of the three most active antimicrobial agents, only doxycycline has been used systemically to treat ocular infections due to C. trachomatis, and it has been reported to be the most effective antimicrobial agent that has been utilized. In vitro testing of obligate intracellular pathogens such as C. trachomatis presents unique problems. Utilization of several methods of testing may help to identify antimicrobial agents with improved clinical efficacy, particularly in the treatment of ocular trachoma.


Mechanisms of maternal-fetal transmission of hepatitis B virus. In a prospective study of maternal-fetal transmission of hepatitis B virus in 125 healthy mothers who were carriers of hepatitis B surface antigen (HBsAg), preliminary results showed that the most important determinant in such transmission was the presence of hepatitis B e antigen in the mother. HBsAg was detectable by solid-phase radioimmunoassay in 33% of amniotic fluid samples, 50% of cord blood samples, 71% of breast milk samples, and 95.3% of samples of gastric contents from newborns. The presence of HBsAg in gastric aspirate from the infants immediately after birth in almost all cases suggests a universal mechanism of infection by the oral route during delivery. In light of these findings, precautions such as possible elective cesarean section, routine gastric aspiration of the newborn, avoidance of breast-feeding, etc., should be taken to avoid perinatal transmission.


Differences in antibodies to the surface components of mumps virus after immunization with formalin-inactivated and live vaccines. Military recruits with or without antibodies to mumps virus were immunized with live or formalin-inactivated mumps virus vaccines. Antibodies to the two major surface components of the virus, the hemagglutinin and the hemolysin, were identified separately. Immunization with the live vaccine did not change the humoral immunity in individuals with detectable antibodies. In seronegative recruits immunization with the live vaccine induced an antibody response against both the hemagglutinin and the hemolysin corresponding to the quality of the immune response after natural infection. In contrast, the formalin-inactivated vaccine only induced an antibody response against the hemagglutinin. This effect was found after immunization of both seronegative and seropositive individuals. The latter displayed a selective boosting of titers of hemagglutination-inhibiting antibody. These findings may have relevance for the interpretation of the short-lived immunity after the use of formalin-inactivated mumps vaccine without repeated boosting.


In vitro invasiveness of Yersinia enterocolitica isolated from children with diarrhea. The invasiveness of Yersinia enterocolitica isolated from the feces of children with diarrhea was assayed in cultured human epithelial (HEp-2) cells. Twenty-one of 24 strains were invasive under the test conditions. Infection with Y. enterocolitica was characterized clinically by exudative diarrhea in 11 cases. Polymorphonuclear leukocytes were demonstrated in the feces from all three cases of exudative diarrhea studied. The results suggest a correlation between enteroinvasiveness of Y. enterocolitica, presence of leukocytes in feces, and clinical exudative diarrhea.


Identification of a swine influenza virus (Hsw1N1) isolated from a duck in Hong Kong. An influenza A virus isolated from a duck during a recent surveillance study on commercial poultry from the People's Republic of China and the New Territories, Hong Kong, was shown to possess Hswl antigens related to that of the swine (Hsw1N1) influenza virus. The isolation of an Hsw1N1 influenza virus from ducks indicates that avian species, as well as pigs, may serve as a reservoir of this potential pathogen for humans. The virus was avirulent for ducks, turkeys, chickens, and pigs.


Chloramphenicol: an impatient study of use and abuse. During a six-month period, chloramphenicol was administered systemically to 100 patients and topically to 24 patients who were admitted to the Medical Center Hospital of Vermont, Burlington, Vermont. Seventy-nine percent of the patients receiving the drug systemically were on surgical services, 13% were on the pediatric service, and 8% were on the medical service. In this group, chloramphenicol was administered appropriately in 60.4% of cases as follows: 57.5% on the surgical, 50% on the medical, and 84.6% on the pediatric services. In 19 of 35 instances of inappropriate use on the surgical services, a potentially less toxic antibiotic could have been chosen. Eight cases were treated inappropriately because of dosage errors, and in seven cases no antibiotic should have been used. On the medical services all inappropriate use was due to underdosage, and on the pediatric service there was one case of incorrect dosage and one instance in which a less toxic antibiotic could have been chosen. Ophthalmological use of the drug accounted for all topical use. Of 24 patients treated, 21 received the drug for prophylaxis and three for therapy.


Remissions induced in hereditary angioneurotic edema with an attenuated androgen (danazol): correlation between concentrations of C1-inhibitor and the forth and second components of complement. Serum concentrations of antigenic and functional C1-INH increased in patients in whom remissions from attacks of HANE were induced with danazol. The levels of C4 were directly related to serum concentrations of C1-INH antigens up to a concentration of about half the C1-INH found in normal plasma; at this point, the C4 concentrations were in the normal range and no longer correlated well with C1-INH concentration. Serum C2 levels correlated less well with C1-INH concentration. In normal serum there was a poor correlation between C1-INH, C4, and C2 levels, suggesting that C1-INH is normally present in excess of the amount needed for normal C4 levels. The increments in serum C1-INH were related to the dose of danazol.


Modification of experimental renal hypertension in the rat by indomethacin and hydralazine. The effects of pretreatment with l, H, and a combination, Hl, were assessed in rats made hypertensive by LRA. SBP, PRA, and urinary sodium and potassium excretion were measured 7 days and 1 day before LRA and 2 and 7 days after LRA on a fixed sodium diet. SBP increased 2 days after LRA in C rats, l- and Hl-treated rats but not in H-treated rats. The elevation of SBP was higher in the l group than in the C group. Hl showed a greater increase than H but less than C. PRA levels did not correlate with changes in SBP. PRA first increased 7 days after LRA. A highly significant decrease in sodium and potassium excretion was observed 7 days after LRA in C and l-treated rats. The data suggest that hydralazine may control blood pressure in this model by preventing sodium retention or, alternatively, that it may reduce blood pressure by direct peripheral vasodilation. Since natriuresis and vasodilation are two well-known effects of PGs, the results are compatible with the possibility that l exerted its noxious effect by inhibiting the synthesis of these compounds. It is also suggested by these studies that the renin angiotensin system does not play a central role in the acceleration of hypertension after l administration.


Rheumatoid factor interference with the latex agglutination test for fibrin degradation products. The latex agglutination test for FDP is widely employed clinically to aid in the diagnosis of DIC and other conditions. Of sera containing RF, 93% demonstrated positive FDP latex agglutination tests. Reducing agents in all instances destroyed the RF agglutinating capability. Futhermore, 86% of sera positive for FDP and RF became FDP-negative following reduction. Therefore RF was responsible for false-positive FDP latex agglutination tests in the majority of patients. Reduction of patient sera is a rapid, simple method to distinguish a positive FDP test from a false-positive due to RF.


Effects of iron on the absorption and retention of lead. An inverse relationship between lead retention and dietary iron content has been suspected for many years, but the reasons for this association remained unknown. In rats, the state of body iron repletion had significant effects on the absorption of lead but no effect on lead excretion. Intraluminal iron decreased the absorption of test doses of lead from the small intestine in a dose-related manner. We postulated that this occurred because the two metals competed for similar binding sites on intestinal mucosal proteins which were important in the absorptive process. In vivo, both lead and iron bound to two heat-stable intestinal mucosal fractions, particularly the higher-molecular-weight fraction. Addition of iron to test doses of lead markedly diminished the amount of lead bound by the high-molecular-weight fraction. Further investigation revealed that this fraction, with a molecular weight of approximately 370,000, bound both lead and iron. Shared binding sites on this protein may explain why dietary iron decreased lead absorption and iron deficiency increased it.


Migration of leukocytes to human nasal mucosa. In order to perform their antimicrobial function PMN must be able to migrate from capillaries to tissues and mucusal surfaces. We found that cellophane squares placed against the nasal septum can stimulate a local cellular response resulting in the migration of granulocytes to the surface of the squares. Upon removal of the squares, adherent cells can be stained, identified, and quantitated. Studies in which the cellophane squares are left against the septum for 5 min reveal a dense monolayer of granulocytes (greater than 6 per 70 micrometer2) on only 7% +/- 2 of the surface of the square. After 2 hr against the nasal septum, a dense monolayer of granulocytes was found on 87% +/- 10 of the surface of the cellophane square. This technique provides a simple and noninvasive method for in vivo measurement of leukocyte migration.


Temporal relationships between urinary salt retention and altered systemic hemodynamics in dogs with experimental cirrhosis. In the present study, we undertook to examine the relationship between urinary sodium retention and systemic hemodynamics in dogs with experimental portal cirrhosis induced by the sporadic feeding of dimethylnitrosamine. Sodium handling was studied by blanace techniques; plasma volume was measured serially with Evan's blue; and CO, blood pressure, CVP, and PVR were monitored through indwelling catheters. Six dogs were studied while standing quietly in a Pavlov sling, in a serial fashion starting 4 weeks after drug administration and continuing for some 3 months thereafter, until all dogs developed cirrhosis and ascites. Urinary sodium retention commenced generally between the ninth to twelfth week following the initation of treatment, but renal perfusion remained normal. Plasma volume expansion was noted within 1 week following the onset of sodium retention. Ascites was generally detected about 2 weeks following the initiation of sodium retention. No alteration in CO or PVR could be detected until ascites was present in significant amount. At that time, CO rose and PVR fell by about 20%. ABP tended to fall during the period of observation, but this was not significant. The initiation of sodium retention in this canine model does not depend on antecedent changes in CO or PVR.


Chemotaxis of human polymorphonuclears in vitro. V. Role of the nonsegmented neutrophils and of the experimental conditions in the impairment of chemotaxis observed during bacterial infections. Chemotaxis of human leukocytes was studied in vitro with a microfilter having pores of 3 micrometer used as a substrate for the gradient. Under these conditions, nonsegmented neutrophils did not reach the compartment filled with the attractant, but a significant proportion of them did so when filters with larger pores were substituted. When leukocytes from infected patients were tested with the usual 3 micrometer pore filters, chemotaxis was reduced (as previously shown), but less markedly and less frequently in simultaneous experiments with larger pores. In experiments performed under agarose layers instead of filters, nonsegmented neutrophils responded normally to chemoattraction, again suggesting that their impaired migration in filter experiments was a matter of pore size. When leukocytes from infected patients were assayed under agarose, no impairment occurred; on the contrary, a slight increase in both chemotaxis and random motility was observed. It was therefore concluded that some published cases of impaired neutrophil chemotaxis in infection might be due to technical bias related to pore size.


Comparison of polymer, glucose, and hydrostatic pressure induced ultrafiltration in a hollow fiber dialyzer: effects on convective solute transport. Ultrafiltration induced by (1) poly(sodium acrylate), (2) glucose, and (3) hydrostatic pressure was studied in a hollow fiber dialyzer. Poly(sodium acrylate) added to dialysate induced large amounts of ultrafiltration without crossing the dialyzer membrane. Sodium ions of the acrylate polymer were osmotically active but were held in dialysate by the impermeant anionic polymer. The hydrostatic pressure equivalent of osmotic pressure induced primarily by the sodium ions approximated that predicted for a completely impermeant molecule. The apparent (net) sieving coefficients for vitamin B12 observed during polymer and hydrostatic ultrafiltration studies were both significantly higher than that observed during glucose ultrafiltration but did not differ from each other. These studies suggest that sodium salts of polyanions can provide an osmotic driving force to yield large amounts of ultrafiltration in dialysis systems and yet not cross the membrane. The studies also suggest that relatively less efficient convective transport with glucose as compared to hydrostatic pressure is neither a membrane phenomenon nor a characteristic of all osmotic pressure induced ultrafiltration. Relatively low effective solute sieving appears to be associated with osmotic induced ultrafiltration with a permeant solute. Under such conditions it is proposed that molecular interaction within the membrane impairs convective transport.


Carbon dioxide effects on erythropoietin and erythropoiesis. The addition of carbon dioxide during a short bout (6 to 24 hr) of hypoxia suppresses the production of Ep. The effects of carbon dioxide on Ep production and erythropoiesis were determined in hypoxic rats over a 6-day period. Carbon dioxide suppressed both renal and extrarenal Ep production induced by hypoxia. However, rats exposed to a hypoxic environment with 5% CO2 became as polycythemic as rats exposed to the same hypoxia without CO2. This may result from the following. (1) A factor other than Ep is involved in stimulating erythropoiesis in these animals. (2) The large amount of Ep produced during hypoxia is in excess, and only a small amount is needed to compensate for the hypoxia by producing increased numbers of RBCs. (3) A significant degree of hemoconcentration occured, resulting in the increased number of RBCs observed.


Renal biosynthesis of prostaglandin E2 and F2alpha: dependence on extracellular potassium. Since recent investigations have shown elevated urinary PGE2 and polyuria in hypokalemic animals which were reversed by PG synthesis inhibition with indomethacin, studies were undertaken to examine the effects of extracellular [K+] on renomedullary PG production in vitro. Slices of rabbit and human renal papilla were incubated in Krebs-Ringer HCO3- buffer, 95% O2-5% CO2, glucose 10 mM, HSA 4 gm/100 ml, for 30 min at 38 degrees C, with and without 1-14C-AA (10 micrometer). Measurments were made of total endogenous iPGE2 and iPGF2alpha production and radioactive AA leads to PGE2. In rabbit renal medulla values for iPGE2 (nmol/gm/30 min) were 252 +/- 20 at [K+] 0; 182 +/- 17 at [K+] 2.5 mEq/L; 163 +/- 18 at [K+] 5.5; and 129 +/- 17 [K+] 9.0 (p less than 0.005). iPGF2alpha was unaltered by changes in media potassium concentrations (6.8 +/- 0.9 nmol/gm/30 min at [K+] 0 and 6.2 +/- 0.8 at [K+] 9.0 MEq/L). In the human renal medulla iPGE2 was 9.5 +/- 1.6 nmol/gm/30 min at [K+] 0; 5.0 +/- 0.7 at [K+] 2.5 mEq/L; 5.3 +/- 0.3 at [K+] 5.5; and 4.6 +/- 1.0 at [K+] 9.0 (p less than 0.05). AA leads to PGE2 (nmol/gm/30 min) was 3.21 +/- 0.92 at [K+] 0; 2.47 +/- 0.57 at [K+] 2.5 mEq/L; 1.30 +/- 0.30 at [K+] 5.5; and 0.76 +/- 0.4 at [K+] 9.0 in rabbit medulla (P less than 0.005). It is postulated that direct stimulation of papillary PGE2 biosynthesis by low extracellular [K+] impairing the cAMP-generating response to vasopressin could represent the initial event in the pathogenesis of vasopressin-resistant polyuria.


Properties of fibrinogen-antigenic material on the rheumatoid synovial membrane and in the rheumatoid synovial fluid. Fibrin deposits on rheumatoid synovial membranes and fibrinogen-antigenic material in rheumatoid synovial fluid were found to be identical by crossed immunoelectrophoresis into immunoglobulin against fibrinogen, by SDS-polyacrylamide gel electrophoresis, and by gel filtration on Sepharose CL 6B. The material was found to be neither fibrinogen nor fibrin, but degradation products. One of the fragments was purified by preparative agarose electrophoresis, and the physicochemical properties of this fragment were found to be different from those obtained by plasmin digestion of fibrinogen or fibrin. This indicates that other proteases than plasmin are responsible for the degradation products. The material was easily degraded by plasmin to D- and E-antigenic end products, identical to those obtained by plasmin digest of fibrinogen. The solubility of the material was poor in synovial fluid compared to serum and buffer. On the basis of these results, it is suggested that the fibrinlike material on the synovial membrane represents fibrinogen degradation products from the inflamed tissue. These products are likely released into the synovial fluid, and when their concentration here exceeds their solubility, they precipitate on the synovial membrane.


Effects of acute and chronic splenectomy on experimental acute renal tubular lesions. The first half of this study describes the effects of acute splenectomy on epinephrine-induced ATL in the dog. Renal morphology and hematocrit were compared in 12 dogs without splenectomy (group I), six dogs with antecedent splenectomy (group II), and seven dogs with antecedent splenectomy after splenic contraction was induced by topical application of epinephrine (group III). Splenectomy was performed in groups II and III 20 to 30 min prior to epinephrine infusion; all three groups received equal infusions (4 microgram/kg/min) for 6 hr before the kidneys were harvested. ATL and renal congestion were consistently severe in group I but infrequent and less severe in groups II and  III. The second half of this study describes the apparent protective effect of chronic (2-week) splenectomy on epinephrine-induced ATL. Renal morphology and hematocrits were compared in 13 intact dogs (group IV) and 10 dogs splenectomized 2 weeks before the epinephrine infusion (group V). The severity of the ATL and the degree of renal congestion were significantly less in the chronically splenectomized dogs. This chronic protection afforded by acute and chronic splenectomy observed after epinephrine infusion remains unclear.


Potentiation of polymorphonuclear leukocyte motile functions by 2,3-dihydroxybenzoic acid. DHB potentiates PMN phagocytosis of opsonized lipopolysaccharide-coated PO droplets by 53% to 45% and chemotaxis by 36% to 10% at 10-3M and 10-4M concentrations, respectively. The effect is reversible in vitro. In the presence of DHB, PMNs released significantly less superoxide and H2O2 to the extracellular media but were able to oxidize 1-14C-glucose normally during phagocytosis. Although iodination of opsonized particles was decreased in the presence of DHB, the PMNs were able to kill Staphylococcus aureus 502A normally. These results support the hypothesis that directed cell movement and phagocytosis can be enhanced by protecting the PMN membrane against auto-oxidative damage from scavenging superoxide and H2O2 by means of DHB.


Effects of glucocorticoids on osteoclast-activating factor. Glucocorticoids lower the serum calcium in patients with hypercalcemia due to myeloma and related lymphoproliferative disorders. OAF is a potent bone-resorbing lymphokine which is probably responsible for the bone lesions and hypercalcemia which occur in patients with these hematological neoplasms. In this study, we have examined the effects of cortisol on the production of OAF and its biological activity in order to clarify the mechanism of action of glucocorticoids in lowering the serum calcium in these disorders. The effects of OAF-containing media on bone resorption were inhibited by cortisol at concentrations from 10-5M to 10-9M. In contrast, OAF production was not inhibited by cortisol at concentrations less than 10-5M. These data support the hypothesis that glucocorticoids inhibit the effects of OAF in vivo primarily by a direct effect on bone resorption.


Changes in platelet function during hemodialysis. Platelet function was studied in 34 patients during 74 hemodialyses by means of a Cordis-Dow hollow fiber hemodialyzer (CDAK-4) with anticoagulation by porcine mucosal heparin. The mean arterial platelet levels fell 11% from predialysis values and remained stable throughout a 5 hr hemodialysis session. After 30 min of dialysis, the platelet concentration in afferent and efferent limbs of the dialyzer were similar, although retention of leukocytes was apparent. As measured by platelet aggregometry, heparin was clearly shown to potentiate the extent of aggregation induced by low concentrations of ADP. Platelets of the dialyzer afferent limb were less aggregable than normal and resistant to aggregation induced by submaximal concentrations of ADP or epinephrine. Platelets of the dialyzer efferent limb were aggregable only after excessive stimuli of 50 micrometer ADP or 10 micrometer epinephrine. These findings suggest that direct contact between dialyzer fibers and platelets or rheological effects led to impaired platelet function but that most platelets are not irreversibly injured.


Comparison of the metabolism of alveolar macrophages from humans, rats, and rabbits: phorbol myristate acetate. Metabolic activities of unstimulated or stimulated AMs from humans, rats, and rabbits were examined and compared in vitro. Rates of oxygen consumption, chemiluminescence, and glucose (1- or 6-14C) oxidation by unstimulated AMs from these three species increased following stimulation of the AMs by bacteria or PMA. Although the absolute metabolic responses of AMs from humans, rats, or wild rabbits were different, the metabolic activities from each species were nearly identical when compared on the basis of protein content of the cells. In contrast to the enhanced biochemical responses of AMs from humans, rats, or wild rabbits, stimulated AMs from certain commercially supplied rabbits failed to increase their metabolism. The failure of AMs from these rabbits to respond metabolically was probably due to an acquired abnormality resulting from their care and storage at the supplier. The defect was associated with the presence of large numbers of Bordetella bronchiseptica organisms in the lavage effluents from these commercially supplied rabbits. This abnormality in metabolism of AMs was reversed following prolonged residence of the rabbits in the laboratory, and the correction of the defect was accompanied by a disappearance of B. bronchiseptica from the lavage fluid. The results comprehensively compare and contrast the metabolism of AMs from humans and animals and emphasize the need to document the appropriateness of animal models before using them to predict biologic reactions of humans.


Excretion of porphyrins in urine and bile after the administration of delta-aminolevulinic acid. Excretion of porphyrins into bile and urine after intravenous injection of delta-ALA was studied in three patients with catheters inserted into the bile duct because of biliary obstruction and in two healthy volunteers. Excretion of porphyrins into bile increased in response to increasing doses of delta-ALA--up to 18 mumol/kg. On the other hand, excretion into urine reached a constant rate at 2 to 4 mumol/kg delta-ALA and did not increase further with larger doses. These findings suggest that transport of porphyrins across the liver cell membrane to the blood must be an important factor in determining the rate of excretion into the urine. After administration of delta-ALA,excretion of coproporphyrin III into urine increased more than that of coproporphyrin I. As a result, the former was the predominant form of urinary coproporphyrin. When radioactive delta-ALA was administered intravenously, far greater radioactivity was recovered in urine as coproporphyrin III than as coproporphyrin I. These results indicate that only a small portion of urinary coproporphyrin I is derived from the liver. A possible source of coproporphyrin I may be erythropoietic tissues, since the amount of urinary coproporphyrin I was considerably decreased in patients with severely suppressed erythropoiesis.


The contribution of glucose to alanine metabolism in man. We have studied by tracer technique the interconversion of the carbon skeleton of alanine with that of glucose. The data analysis is in terms of renewal theory rather than traditional compartmental analysis. This eliminates the need for estimation of compartment size, which is particularly difficult to determine in the case of alanine. In addition, the conversion rates between the two substances are found by considering the two components which are responsible for the determined radioactivity curves, namely, the first conversion of the labeled carbon and its subsequent movement in the product compound. The subjects of the study were for the most part underweight but had been hospitalized and eating a standard hospital diet for at least 3 days prior to the studies. Our data indicate that nearly twice as much carbon from glucose is cycled to alanine as is recycled from alanine back to glucose after a 14 hr overnight fast. Small amounts of glucose suppress the alanine-glucose arm of the cycle but probably do not change the glucose-alanine conversion. The contribution of glucose carbon to alanine metabolism is significant and appears to be immediately influenced by the magnitude of glycolysis.


Speech audiometry in acoustic neuroma.

Speech audiometry in acoustic neuroma. The importance of speech audiometry in cases of sensori-neural deafness has been stressed. Four cases have been described clearly elucidating this point. Speech audiometry is within the means of most practising otologists. The appropriate apparatus is not expensive, nor is the method excessively time-consuming. In acoustic neuroma the damage to the cochlear nerve fibres may produce very little reduction in the hearing threshold level for pure tones, but a disproportionately large reduction in the discrimination score, often when the tumour is large enough to be causing brain stem compression. The disproportion is an important indicator to the presence of retro-cochlear pathology, of which acoustic neuroma is the most likely cause, a diagnosis which must be considered in every case of unilateral sensori-neural deafness.


Otomycosis: a survey in the eastern province of Saudi Arabia. The Eastern Province of Saudi Arabia is characterized by a high perennial relative humidity and atmospheric pressure. One hundred and forty-eight cases clinically suspected of being otomycotic were examined by culture over a period of 13 months; 120 gave positive results and yielded 131 fungal isolates, of which 110 were single infections and 10 mixed infections of two or more fungi. A. niger was the most common (51.15%), then A. flavus (18.32%) Penicillium notatum (5.34%), C. albicans and A. terreus (each 4.58%) A. candidus (3.82%), Mucor spo (2.29%), Alternaria spo and A. clavatus (each 1.53%) and A. versicolor (0.76%). The patients were of 13 different nationalities, mostly labourers and people of low socio-economic standard. Males were affected more than females and ages ranged from 2 to 58 years. Thus racial factors, sex and age have no bearing on otomycosis. Only 8 of the 120 positive cases were affected bilaterally. The role of relative humidity and high atmospheric pressure was briefly discussed.


Effect of atherosclerosis and hypertension on arterial epistaxis. Eye fundus examination in twenty cases of hypertensive nose bleeding was carried out to evaluate the effect of hypertension and atherosclerosis on epistaxis. Arteriolar attenuation, atherosclerosis and venous congestion were detected in most of the cases. None showed haemorrhages or exudates. Hypertension and atherosclerosis seem to maintain and increase the severity of epistaxis, once it has been initiated by other factors.


Drug-induced corrosive injury of the oesophagus. Five patients are described who had retrosternal pains following the consumption of CetiprinR tablets. The pains increased so markedly within a few days that, initially, solid foods and, subsequently liquid foods also were impossible to swallow. Typically the history was of the comsumption of a tablet in the evening or night without fluids and the pains lasted 2--3 weeks. A marked corrosive injury of the middle third of the oesophagus was shown at oesophagoscopy in each case, but the mucosa of the lower one-third of the oseophagus was normal. Gastro-oesophageal reflux was not demonstrated radiologically in any of the patients. None of the patients developed a stricture of the oesophagus. The most likely alternative in the differential diagnosis was a foreign body. Oesophagoscopy should be performed on any patient in whom such pains persist for more than 4--5 days, even if the X-rays are normal. The physician should advise his patients to take tablets or capsules with fluids. This is especially important if the drug is taken in the evening or at night. CetiprinR tablets should be taken in the evening while the patient is still upright, and should be taken with fluids. If a corrosive injury does develop, we suggest that treatment should be with cortisone and with agents which protect the oesophageal mucous membranes.


Primary Ewing's sarcoma of the maxilla: a clinicopathological study of four cases. The author reports four cases of Ewing's sarcoma primarily located in the maxilla and emphasizes the rarity of such a primary location and the fact that this series contained cases observed at the Department of Otolaryngology of Padua University during the last three years which, though small, is the largest so far reported. In addition to a review of the world literature on the subject, the problems related to the differential diagnosis, in particular from reticulum cell sarcoma of bone, neuroblastoma and olfactory neuroblastoma are discussed. The cases reported are accurately described and histologically documented. Treatment of Ewing's sarcoma is also discussed and, according to the author, the elective therapeutic procedure should consider local irradiation and intermittent but prolonged systemic chemotherapy, leaving mutilating surgery only for recurrent tumours.


Mucocele of the paranasal sinuses in cystic fibrosis. Two children below 9 years of age with mucocele and cystic fibrosis are reported. Mucocele in this age-group is very rare and is probably pathognomonic of cystic fibrosis.


Pharyngeal rhabdomyoma: an unusual presentation. A case of pharyngeal rhabdomyoma is reported with the unusual presenting symptom of haemoptysis. After complete excision of the lesion, the(71-year-old) patient remained tumour-free until his death from heart disease 19 months later. Seven other published cases of pharyngeal rhabdomyoma are reviewed together with 27 other reported extracardiac adult rhabdomyomas which, with a single exception, occurred in the head and neck region.


Lipoma of the hypopharynx. A case report and a review of the literature. The clinical and pathological-anatomical features of lipomas of the hypopharynx, based on a review of 23 cases presented in the literature and exemplified by a new case, are discussed. The tumour may be solitary or multiple and appears mostly in men over the age of forty. Although it may reach a considerable size, it may be asymptomatic, until it appears in the mouth or suffocation occurs. Recurrences are rare but metachronous multiple lipomas may appear. Long-term follow-up is therefore recommended. The difficulties of differential diagnosis between lipomas and well-differentiated liposarcomas are discussed.


Second primaries in cases of cancer of the larynx. The incidence of second primaries in 1,600 patients treated with radiotherapy for cancer of the larynx is reviewed. Carcinoma of the lung is the most frequent second primary with a significantly higher incidence in supraglottic laryngeal cancer. Because the follow-up of this irradiated population is limited it is not yet possible to estimate the risks of radiation-induced cancer in the entire life span following radiation treatment of cancer of the larynx.


Angiofollicular lymph node hyperplasia.

Angiofollicular lymph node hyperplasia. One case of angiofollicular lymph node hyperplasia simulating a salivary gland tumour is presented. In a review of the literature containing some 220 cases, 29 cases in the neck were found. A survey of these 29 cases is given, and another two cases of special oto-rhino-laryngologic interest are mentioned. Furthermore, a description of the tumour and a brief discussion of aetiology and differential diagnosis are given.


Plasma squalene: lipoprotein distribution and kinetic analysis. Plasma squalene concentration is increased in hypertriglyceridemia. In 24 normotriglyceridemic and 12 hypertriglyceridemic subjects, whole plasma squalene correlated strongly with plasma triglyceride (r = 0.973, P < 0.001) in the latter. In normal postabsorptive plasma, squalene was found in each lipoprotein fraction, 50.8% in very low density lipoprotein, 25.6% in low density lipoprotein, and 23.6% in high density lipoprotein. When plasma triglyceride was increased by dietary intake in humans or by experimental diabetes in rats, plasma squalene increased correspondingly. Conversion of [(14)C]mevalonic acid into [(14)C]squalene and kinetic analysis of [(14)C]squalene die-away curves were studied in 17 subjects. Hypertriglyceridemia significantly increased the estimated metabolically active plasma squalene pool. This together with an increase in radioactivity of squalene (dpm/ml plasma) in hypertriglyceridemia suggested that squalene production was increased. Squalene specific activity curves in lipoprotein fractions from four chylomicronemic subjects demonstrated that each fraction had newly synthesized squalene and that total plasma squalene kinetics represent the composite of several individual die-away curves. We conclude that squalene in whole plasma and in lipoprotein fractions varies directly with triglyceride content. Hypertriglyceridemia expands the plasma pool of metabolically active squalene, and each lipoprotein fraction contains squalene that is metabolically active in cholesterol synthesis.


Sterol synthesis and CO2 production from mevalonate in calves. Nonruminating male Holstein calves were fed a reconstituted milk containing 11.7% nonfat-dried-milk solids and 3.5% beef tallow. Calves were slaughtered at 17 weeks of age. Samples of perirenal adipose tissue, liver, muscle, small intestine, kidney cortex, and kidney medulla were assayed in vitro for sterol synthesis and production of (14)CO(2) from [2-(14)C]mevalonate. Of the tissues tested, adipose tissue and kidney medulla produced nonsaponified lipids at the greatest rates; kidney cortex and liver at half the rate of adipose tissue; muscle and jejunum at one-eighth the rate of adipose tissue; and ileum at a negligible rate. The amount of (14)C in squalene, lanosterol, and cholesterol of the nonsaponified lipids of each tissue was determined by thin-layer chromatography. Proportions of (14)C in cholesterol to (14)C in total nonsaponified lipids ranged from 30% to 59%; squalene, from 5% to 27%; and lanosterol, from 11% to 59% of the total nonsaponified lipids present. The rate of CO(2) production by the "trans-methylglutaconate shunt of mevalonate metabolism" was determined. Kidney cortex displayed the greatest shunt activity, producing 15-80-fold more CO(2) than any other tissue tested. Ileum, jejunum, skeletal muscle, and kidney medulla had similar shunt activities; liver sections had less shunt activity, and no shunt activity was detected in adipose tissue. These data reveal a shunt for mevalonate utilization that does not lead to sterols and also show that the kidney is important in the sterol and nonsterol metabolism of mevalonate.


Preparation of [24,25-3H] cholesterol. Oxidation in man as a measure of bile acid formation. In order to devise a convenient method for measuring the rate of formation of bile acids from cholesterol in man, [24,25-3H] cholesterol was prepared by catalytic tritiation of desmosterol where the delta5-unsaturation was protected by conversion to the 3 alpha, 5 alpha-cyclosterol-6-methyl ether. It was shown that tritium in the purified labeled sterol was located exclusively in the side chain. Measurements of 3H2O and the specific activity of plasma cholesterol at timed intervals up to 96 hours after administration of the tracer to three subjects afforded values for cholesterol oxidation (equals bile acid formation) in good agreement with accepted figures for bile acid formation determined by other techniques.


Gangliosides of human, cat, and rabbit spinal cords and cord myelin. Gangliosides were isolated from whole spinal cords and cord myelin of human, cat, and rabbit by a revised methodology. The method included the sequential application of DEAE-Sephadex column chromatography, base treatment, Sephadex G-50 column chromatography, and finally Iatrobeads column chromatography. The human whole spinal cord was found to contain about one-tenth of the ganglioside concentration as in cerebral gray matter and about one-third of that in cerebral white matter. Low levels of gangliosides were also found in cat and rabbit whole cords. Only N-acetyl neuraminic acid could be detected in the ganglioside fractions of all three species. The whole cords also possessed unique ganglioside patterns when compared with the patterns of cerebral tissues. The most prominent and consistent features were the reduced concentration of Gd1a and increased amounts of Gm3 and Gd3. Human, but not cat and rabbit, spinal cord also contained Gm4 as one of the major gangliosides. Myelin prepared from the spinal cords of all three species also contained gangliosides. The amounts were only about half of those in the respective cerebral white matter myelin. The cord myelin ganglioside pattern was generally similar to the cerebral white matter myelin within the same species. Gm1 was the most abundant ganglioside in the cord myelin. Gm4 was found to be highly enriched only in myelin prepared from human sources.


The sources of rat biliary cholesterol and bile acid. The precursor sources of bile acid and bile neutral sterol were evaluated in the rat using Triparanol to inhibit the terminal reduction in the synthesis of cholesterol. During the initial period of Triparanol administration, the accumulation of hepatic desmosterol acts to segregate relatively newly synthetic hepatic sterol from the bulk of the equilibrated sterol mass. Biliary excretion of newly synthetic sterol can then be determined in acute studies, assuming no great differences between desmosterol and cholesterol as precursors of biliary neutral sterol or bile acid. It has been determined in this model that newly synthetic sterol comprises a mean of about 28% of the total biliary neutral sterol output. This fraction fell when hepatic cholesterogenesis was suppressed by prior cholesterol feeding. By using this approach in conjunction with the administration of labeled mevalonate to a renal pedicle-ligated rat, it was possible to calculate the amount of bile acid produced from either newly synthesized sterol or the equilibrated sterol pool. It has been estimated that the bulk of bile acid synthesis arises from this equilibrated source when these determinations were made within two hours of creating the fistula. With more prolonged fistula times, more of the bile acid originated from the newly synthesized sterol.


Re-evaluation of lipogenesis from dietary glucose carbon in liver and carcass of mice. We have estimated rates of fatty acid synthesis from glucose carbon and from all 2-carbon units in liver and carcass of mice using [U-14C] glucose and 3H2O under four different nutritional states. The liver synthesized only a small fraction (2--9%) of the fatty acids that were formed from glucose carbon in mice that were fasted 24 hr, fasted--refed, or fed ad libitum. However, in fed-refed mice, the liver's role increased and now accounted for 40% of the fatty acids that were formed from glucose carbon. Under the latter conditions (fed-refed), the liver synthesized 50% of the fatty acids that were formed from all 2-carbon units. At least five-sixths of all the fatty acids synthesized de novo in the fed-refed mouse were derived from carbon fed in the glucose test meal. These studies, in contrast to most earlier studies, provide direct evidence in mice of the major contribution that dietary carbohydrate makes, especially in the liver, to the synthesis of fatty acids. In addition, we have shown that lipogenic inhibition (fasting) and activation (feeding) are most marked in liver and greater for glucose than for non-glucose-carbon. Possible implications for dietary control of carbohydrate-induced hyperlipemia and obesity are discussed.


The effect of dietary fat supplements on cholesterol metabolism in ruminants. The serum cholesterol on ruminant animals rises when supplemental fat is fed in a form that ensures the absorption of long-chain fatty acids. The effects of these fat supplements on cholesterol metabolism have been studied in sheep and goats. The proximal part of the small intestine was the major site of sterol synthesis in sheep. Supplementing the diet with fat significantly enhanced sterolgenesis in the small intestine both in vivo and in vitro, whereas in vitro sterolgenesis appeared to be suppressed in the liver. Increased intestinal sterolgenesis was seen with several varieties of fat, but was greatest when palm oil was fed. The reciprocal findings in the intestine and liver may reflect the increased requirement for cholesterol for the transport of triglyceride in chylomicrons and the secondary inhibiting effect of this cholesterol on sterol synthesis in the liver. Dietary fat supplementation did not alter the excretion of neutral steroids in the feces of goats but did not cause a marked reduction in the excretion of acidic steroids which may have been due to the decreased formation of sterols in the liver. In two lactating goats in which an injection of [14C] cholesterol was followed by daily intraruminal administration of labeled cholesterol, fat supplementation lowered the specific radioactivity of cholesterol in alimentary particles and in milk, being consistent with an increase in intestinally synthesized cholesterol. The hypercholesterolemia that develops in fat-fed ruminants appears to be primarily due to an increased intestinal biosynthesis of cholesterol but may also be partly due to a decreased fecal excretion of bile acids.


Quantitative microanalysis of perbenzoylated neutral glycosphingolipids by high-performance liquid chromatography with detection at 230 nm. A method is described which permits the quantitative microanalysis of glycosphingolipids in the picomole range by HPLC of their perbenzoylated derivatives with detection at 230 nm. A linear gradient of 1 to 20% dioxane in hexane is used to elute from a Zipax column derivatives that contain up to four sugar residues. Residual absorption due to dioxane is negated by directing the solvent gradient through a pre-column, pre-injector high-pressure reference cell. This  path generates a horizontal baseline with a negative and a positive deflection at the beginning and end of the gradient, respectively. Neutral glycosphingolipids can be quantitated either with N-acetyl-psychosine as internal standard or by comparison of peak areas to those of external standards.


Enzymatic assay for cholesterol ester hydrolase activity. A rapid and accurate method is described for the assay of cholesterol ester hydrolase (CEH) activity. Aliquots of the enzyme-substrate incubation mixture are extracted into isopropanol. The free cholesterol concentration in each extract is determined enzymatically using a single aqueous reagent containing cholesterol oxidase and peroxidase. The free cholesterol remaining after the cholesterol ester hydrolase-catalyzed esterification is converted to delta 4-cholestenone and hydrogen peroxide (H2O2); peroxidase couples H2O2 with phenol and 4-amino-antipyrine to yield a stable rose-colored product absorbing at 500 nm. The method is highly reproducible and the values correlate well with those obtained with the chromatographic radioassay of CEH activity.


Microanalysis of brain lipids: multiple two-dimensional thin-layer chromatography. The techniques described allow the quantitation of cholesterol, cerebrosides, sulfatides, ethanolamine phospholipids, phosphatidylcholine, -serine, -inositol, and gangliosides on 500 micrograms of lipid. Lipid extraction required sonication. Separation of the lipid classes was performed on TLC glass plates (10 x 10 cm) coated with silica gel HPTLC 60 F 254 Merck using one multiple two-dimensional chromatography. Most of the methods used for quantitation were standard methods that had been scaled down. The procedure was applied to study regional differences in the central nervous system, to analyze cell membranes or subcellular particles, or to analyze pathological biopsies in the central and peripheral nervous systems.


Re-evaluation of the 3 alpha-hydroxysteroid dehydrogenase assay for total bile acids in bile. A review of the 3 alpha-hydroxysteroid dehydrogenase method for determining the concentration of total bile acids in bile is described. The optimum conditions for the assay were established with respect to pH, temperature, incubation time, amount of NAD+, and units of enzyme activity required to obtain complete oxidation of the substrate under fixed conditions. Furthermore, the effect of hydrazine hydrate, methanol, and bile volume on the reaction was examined. It was also established that the bile acid concentration in bile samples with a high molar percentage of cholesterol would be overestimated if 3 beta-hydroxysteroid dehydrogenase were present with the 3 alpha-enzyme.


Thresholds and travelling waves for the geographical spread of infection. A nonlinear integral equation of mixed Volterra--Fredholm type describing the spatio-temporal development of an epidemic is derived and analysed. Particular attention is paid to the hair-trigger effect and to the travelling wave problem.


Selfing in genetic algebras.

Selfing in genetic algebras. The effect of self fertilization on the distribution of genetic types in a population can be represented algebraically by a linear transformation. In this paper the relationship of the transformation to the genetic algebra governing the population is investigated. In particular, the problems of multiple alleles, polyploidy and linked loci are studied.


Pure anterior conduction delay: a variant "fascicular" defect. Based upon electrocardiographic studies of conduction disturbances, the human intraventricular conduction system has been considered trifascicular: a right bundle and a  bidivisional left bundle. Right bundle branch block, left anterior hemiblock, and left posterior hemiblock have been described. Microscopic and endocardial mapping studies, however, do not demonstrate a corresponding anatomical basis of this useful functional concept. Atrial premature beats in our two cases resulted in ventricular aberrancy which strongly suggests an additional form of a functional conduction delay. Such delay is manifest as a narrow QRS with anterior displacement in the horizontal plane but no axis shift in the frontal plane. This aberrancy is important to recognize because it can mimic the ECG findings of true posterior myocardial infraction. We do not postulate, however, a specific fascicle of the left bundle as the anatomic substrate for this recently recognized effect.


The significance of dissociation of conduction in the canine His bundle. Electrophysiological studies in vivo and in vitro. Fractionated His bundle potentials were induced by ischemia or trauma in 30 anesthetized dogs, in vivo. Functional dissociation, i.e., alteration of the activation sequence of portions of these His bundle potentials was demonstrated in vivo as well as in 10 in vitro preparations of the His-Purkinje system. In vivo, plunge wire and electrode catheters were utilized to record from portions of the His bundle. During vagal-induced slowing of the heart rate, atrial pacing or His bundle pacing, His-Purkinje conduction as measured by the H-V interval was constant over a wide range of heart rates, 50-300/min. One or two hours after anterior septal artery ligation, His bundle damage manifested as split His bundle potentials (H, H'). Atrial pacing or proximal His bundle pacing induced H-H' delays with concomitant right or left bundle branch block patterns in ECG leads. However, distal His bundle pacing at comparable or even higher rates produced normal QRS complexes. In other cases, during atrial pacing or with progressive ischemia at a constant rate, H' progressively delayed during the H-V interval or even disappeared into the QRS complex with a concomitant occurrence of right or left bundle branch block. In vitro, a dissected septal preparation was studied containing the His bundle, proximal and distal right bundle and left bundle branches. Normal conduction throughout the His-Purkinje system was observed at pacing rates of 30-220/min. Punctate lesions, anatomically placed above the branching His bundle caused tachycardia-dependent, complete bundle branch blocked with concurrent temporal reversal of proximal and distal His bundle action potentials. These data suggest that ischemic or traumatic lesions in the His bundle may manifest on the electrocardiogram as bundle branch block patterns. From a clinical point of view, a critical site of lesion would markedly increase the liability for A-V blocked although the electrocardiogram alone would not indicate the actual site of lesion. Predestination of fiber tracts and alternative proposals to the pedestination theory are considered to explain QRS aberration due to exclusive His bundle lesions.


Precordial ST-segment mapping 5. Analysis of maps and standard electrocardiograms in patients with inferior myocardial infarction. Measured and derived electrocardiographic parameters pertaining to ST-segment elevations, R and Q wave amplitudes from standard electrocardiograms, and 49-lead precordial maps from ten patients with acute inferior transmural myocardial infarction were analyzed. Sums of ST-segment elevations correlated well with corresponding values derived from various combinations of standard leads expressing inferior ischemic injury. Derived ECG R and Q wave data from maps did not correlate with corresponding parameters from the standard ECGs. Stability of parameters derived from ST-segment elevations over the course of the study and lack of correlation with data expressing changes in the R and Q waves were noted. An analytical pattern such as the one utilized in this study can be used for assessment of therapeutic interventions in the Coronary Care Unit.


Left atrial rhythm in man: an experimental study. Ten patients with atrial septal defect of the secondum variety undergoing diagnostic haemodynamic study were subjected to electrical stimulation of the endocardium of the left atrium using a bipolar pacing electrode catheter. The polarity, frontal plane P wave axis and P wave configuration were analysed from ten scalar 12 lead electrocardiogram (ECG), recorded at 25-50 mm/sec during sinus rhythm and left atrial stimulation. While four patients demonstrated the "dome and dart" appearance of P waves in V1, nine out of ten patients revealed upright P waves in V1 during left atrial pacing; one patient showed inverted P waves in V1-V6. Four patients had negative "P" waves in L1 and only five of ten patients had inverted "P" waves in L1 and V6. All the criteria of left atrial rhythm were present in only one patient. It appears that the "P" waves change during left atrial pacing are variable and that the typical findings of left atrial rhythm are not obtained in all cases. This study was planned because trans-septal left atrial stimulation in the genesis of left atrial rhythm has not been widely reported.


A new test for pacemaker leads: capacitance measurement. A device has been developed which permits in man the measurement of the capacitance of a chronically implanted pacemaker lead at the moment of battery replacement. A large increase in capacitance suggests important body fluid penetration into the lead. This can be due to an insulation defect (caused by a suture or a guide wire during implantation) or to a degeneration of the insulation material or to the lead-design. This fluid penetration should be avoided since it can be responsible for some electro-chemical reactions. Calculated values for the capacitance of a system consisting of an inner and an outer conductor, with two media in between, agree rather well with measured values. It is suggested that the measurement of the capacitance of a pacemaker lead is an additional tool for the evaluation of chronically implanted pacemaker leads. This method can also be of interest for the quality control of pacemaker leads.


The effect of phentolamine on intra-Hisian conduction. A His bundle electrogram was obtained in a 70 year old male with syncopal episodes. A split bundle of His deflection was recorded. After the intravenous administration of phentolamine, a marked shortening of the H-H' interval was observed. This signifies an improvement in conduction at the bundle of His level.


Duchenne electrocardiogram in myotonia dystrophica. The term "myopathic pattern" is applied to the electrocardiographic finding of R/S in lead V1 of more than 1.5 in association with deep Q and prominent R waves in leads V4-V6. Such findings are characteristic of Duchenne's pseudohypertrophic muscular dystrophy and reportedly do not occur in other types of muscular dystrophy or myopathy. The purpose of this paper is to describe a case of myotonia dystrophica with the Duchenne electrocardiographic pattern.


A-V block in accidental hypothermia.

A-V block in accidental hypothermia. His bundle electrocardiography was performed on a patient with accidental hypothermia on whom the standard electrocardiogram (ECG) showed absent P waves, prominent J waves and a slightly irregular rhythm. Sino-ventricular conduction and a prolonged AH interval not responsive to atropine were found. These abnormalities reversed with rewarming.


Sympathetically induced atrial tachycardia. Successful treatment by left stellate ganglion block. An unusual type of atrial tachycardia was observed in a 52-year-old woman. The tachycardia occurred only when the patient kept the left upper limb in the lateral and horizontal position. Propranolol, atropine sulfate, carotid sinus massage and ocular compression were not effective in terminating or preventing the arrhythmia. Left stellate ganglion block has stopped the tachycardia for at least two years. The atrial tachycardia in this patient was thought to be caused by mechanical stimulation of the left stellate ganglion resulting in pacemaker shifting, as has been demonstrated in the canine heart.


Steroid feedback on luteinizing hormone secretion during sexual maturation in the pig. The effects of gonadal secretions on the release of LH and the stimulation of LH secretion by oestradiol have been investigated in newborn male and female miniature pigs; the differences in the feedback action of testosterone in newborn and pubertal male pigs were also studied. Hemi-orchidectomy or orchidectomy of 1-week-old pigs had no effect on the level of LH in the plasma; total orchidectomy significantly reduced the levels of testosterone (P less than 0.01) and progesterone (P less than 0.05). In female pigs ovariectomized at 1 week of age, the concentration of LH in the plasma decreased, with a strong negative correlation between the level of LH and age (r = -0.41; P less than 0.05). The plasma concentration of progesterone was generally low and unaffected by ovariectomy. Orchidectomy and treatment of male pigs, at 1 week of age, with testosterone (6 mg/kg body weight) had no effect on the plasma concentration of testosterone 24 h after treatment. If testosterone propionate was given rather than testosterone, the level of LH was significantly reduced (P less than 0.001) 24 h after the injection and the concentration of testosterone in the plasma corresponded to that found in the intact adult male pig. Treatment with oestradiol or oestradiol benzoate did not affect the concentration of LH. Orchidectomy and treatment of pubertal male pigs with testosterone propionate resulted in a significantly (P less than 0.001) higher concentration of testosterone in the plasma, compared with newborn pigs treated similarly, but the level of LH was unchanged. This suggests that there is a more rapid rate of clearance of testosterone in the newborn than in the pubertal male miniature pig and that the negative feedback of testosterone is not mediated by aromatization in the newborn animal and it declines before or during puberty. Treatment of newborn intact male and female and gonadectomized male pigs with oestradiol benzoate produced similar variations in the plasma level of oestradiol in all groups of animals. In the female pigs, however, a surge-like release of LH was observed 60--72 h after the injection of oestradiol benzoate, suggesting that the stimulatory feedback mechanism can operate soon after birth and that the response is sexually dimorphic.


Relationships between prolactin and follicle-stimulating hormone during early pregnancy and the puerperium. This investigation studies the relationship between the concentrationss of prolactin and FSH in the serum during pregnancy and the puerperium. A single dose of 5 mg bromocriptine during early pregnancy induced a profound fall in the serum level of prolactin with a substantial rise 20 h later. During the initial reduction in the concentration of prolactin, no alteration was noted in the level of FSH but during the subsequent increase in the prolactin concentration, there was a significant (P less than 0.05) decrease in the concentration of FSH. During week 1 of the puerperium, the concentrations of FSH and prolactin were significantly lower in lactating women than in women who were not breast feeding, but there was no significant difference between the concentration of FSH in women who had suppressed lactation with bromocriptine and in those whose lactation was suppressed by non-hormonal methods. when the concentration of FSH was measured every 10 min during a 30 min breast feed, there was a marked but short-lived rise in the serum concentration of prolactin but no change in the level of FSH. These results suggest that an increase in the serum level of prolactin in pregnancy can have a suppressive effect on the production of FSH. Although acute suckling-induced hyperprolactinaemia in the puerperium has no such effect, the maintenance of lactation in the long term does suppress the concentration of FSH in the serum.


Effect of low phosphorus diets on intestinal calcium absorption and the concentration of calcium-binding protein in intact and parathyroidectomized pigs. The effect of changing the dietary concentration of phosphorus on the intestinal absorption of calcium has been studied in conscious pigs each prepared with a Thiry--Vella loop of jejunum. A reduction in the percentage of phosphorus in the diet from 0.7 to 0.3% caused an increase in the efficiency of absorption of calcium from the fluid used to perfuse the jejunal loop in both intact and parathyroidectomized animals. There was a marked increase in the amount of calcium-binding protein (CaBP) in the small intestine of pigs fed the low phosphrous diet. Parathyroidectomy did not affect the amount of CaBP in the small intestine when either the normal or the low phosphorus diets were fed.


Specific suppression of follicle-stimulating hormone secretion in gonadectomized male and female rats with intrasplenic ovarian transplants. Adult male and female rats received an ovarian homotransplant under the kidney capsule or in the spleen 14 days after gonadectomy. After transplantation under the kidney capsule, the high levels of both LH and FSH normally observed after gonadectomy decreased to the levels found in intact male and female rats. After transplantation into the spleen, however, the serum levels of LH increased still further, although a decrease was observed in the level of FSH. In male rats, the concentrations of oestradiol-17beta in the plasma increased from 17 to 56 pg/ml after transplantation of an ovary under the kidney capsule; the concentration was not increased after intrasplenic ovarian transplantation. In female rats with an intrasplenic transplant, the uterine weight did not increase and vaginal smears were not cornified. Administration of oestrogen and progesterone to produce approximately the concentrations found in rats with an intrasplenic transplant did not result in decreased concentrations of FSH. These results suggest that the ovary secretes a substance with specific FSH-suppressing activity, which is not inactivated by the liver.


Uptake and binding of glucocorticoids in fish tissues. Cytosols prepared from the liver and various tissues of goldfish (intact or hypophysectomized) and trout (intact) were incubated at 2 degrees C in the presence of tritiated cortisol or dexamethasone (3 x 10(-9) to 3 x 10(-6) mol/l) with or without a 1000-fold excess of unlabelled steroid. In contrast to mammals, the specifically bound component represented a very low fraction of the total bound steroid retained on DEAE cellulose filters and did not show saturation over a large range of concentrations. The subcellular distribution of [3H]dexamethasone was studied in trout liver after intra-vascular injection of the labelled steroid with and without an excess of unlabelled steroid. The amount of protein-bound steroid in the cytosol again corresponded to a small (4%) proportion of the free steroid. The large reduction in the uptake of tritiated dexamethasone, which was induced in both the cytosol and nuclei by competing unlabelled dexamethasone, was interpreted as evidence for mediated entry across cellular and nuclear membranes. These results indicate that high-affinity binding sites are absent, or present only in very small numbers in cytosol from teleost tissues. The entry of glucocorticoids into the nucleus may not require the hormone to be bound to high-affinity cytosolic receptors unless the binding, though quantitatively small, displays a high rate of turnover.


Effects of an intra-uterine device on uterine cell division and epithelial morphology in ovariectomized mice treated with oestrogen and progesterone. Silk threads placed in the uteri of ovariectomized mice increased cell proliferation in all tissues including regions of the uterus remote from the site of insertion. Many of the effects resembled those produced by oestrogens. An intra-uterine device (IUD) increased luminal and glandular mitosis and produced various degrees of luminal epithelial hyperplasia in untreated animals. In progesterone-treated mice bearing IUD's, luminal and stromal mitosis was increased. Epithelial morphology was not affected or luminal mitosis inhibited in oestrogen-treated animals with IUD's, but stromal and glandular mitosis was increased. After combined treatment with progesterone and oestrogen, stromal mitosis was suppressed at the contact site but was increased elsewhere. Both oestrogen and progesterone suppressed the luminal leucocytosis induced by the IUD. Despite this, the IUD prevented complete progestational differentiation of the luminal epithelium and closure of the lumen. The degree to which IUD-induced abnormalities were observed depended on the hormonal status of the animal at the time of sampling.


Thromboxane B2 and human parturition: concentrations in the plasma and production in vitro. The concentration of thromboxane B2 has been measured in the plasma of women during late pregnancy, during term and pre-term labour, in women with pre-eclampsia and in umbilical cord arterial and venous plasma. In addition, the rates of production of thromboxane B2 in vitro were determined for placental tissues obtained after spontaneous vaginal delivery or elective Caesarean section. The results obtained indicate significant differences during parturition between the sources and controlling mechanisms of thromboxane and prostaglandin production.


An improved method for estimating cholecystokinin in human serum. Because of difficulties encountered in setting up radioimmunoassays for cholecystokinin (CCK) a sensitive and reliable biological method for estimating this hormone is still needed. The principles of such a biological technique and an improvement to it have already been described, but the serum levels of CCK reported were high and the technique required further refinement and validation. The strips of rabbit gall-bladder used to estimate the concentration of CCK increased in sensitivity to standard solutions of CCK over a 6--8 period before stabilizing, but a single sample of serum increased the sensitivity of the strips of gall-bladder to their maximum immediately. These two problems were eliminated by 'priming' the strips of gall-bladder by exposure to two serum samples before exposure to the standard solutions used for production of a dose--response curve. Thirdly, it was discovered that some non-peptide substances in serum possessed CCK-like activity; by extracting all the small peptides from serum with dextran-coated charcoal the residual activity could be measured and subtracted from the total CCK activity. Finally, the activity of CCK in the serum increased during processing before freezing. This increase was eliminated by taking the blood samples into aprotinin which has been shown to cause dramatic reduction in CCK activity in some experiments. When all these factors were taken into account and the technique suitably modified, the mean level of CCK in the serum of ten normal fasting subjects was found to be 28 milli Ivy Dog units/ml (2.4 pmol/ml), which is only one third of that reported previously.


Effects of prostaglandins on the metabolism of cholesteryl ester in rat testes: changes in the synthesis and hydrolysis of cholesteryl ester and the activity of cholesterol side-chain cleavage enzyme. The effects of prostaglandins on testicular synthesis and hydrolysis of cholesteryl esters, the activity of the enzyme involved in cleavage of the cholesterol side-chain and on serum levels of testosterone and LH have been studied. Subcutaneous administration of prostaglandins to male rats caused an increase in the concentration of cholesteryl esters in the testes, a decrease in testicular synthesis and hydrolysis of cholesteryl esters but no change in the activity of the cholesterol side-chain cleavage enzyme. There was also a significant decrease in the serum level of testosterone, but the level of LH was raised. Prostaglandins also affected the fatty acid composition of lipids in rat testicular tissue; cholesteryl esters were found to contain greater amounts of arachidonic (C20:4) and docosapentaenoic (C22:5) acids. These findings suggest that prostaglandins are involved in the turnover of cholesteryl esters in rat testicular tissue and regulate the production of androgens.


Antiandrogenic effects of the pineal gland and melatonin in castrated and intact prepubertal male rats. In castrated prepubertal rats, pinealectomy enhanced the testosterone-induced growth response of the seminal vesicles and melatonin inhibited this effect in a dose-related manner. In entire animals, the serum concentration of LH was increased after pinealectomy with no significant changes in other parameters. Administration of melatonin to intact, pinealectomized rats did not affect the serum concentrations of LH or testosterone but caused a dose-related decrease in the weight of the seminal vesicles. The highest dose of melatonin tested reduced the weight of the ventral prostate gland and the uptake of radioactivity by both the ventral prostate gland and the testes after injection of [5-3H]uridine. It is suggested that the pineal gland and melatonin may exert an antagonistic effect on the biological activity of androgens administered to castrated rats and that melatonin can reduce the growth of the accessory sex organs of intact, pinealectomized rats, in spite of a high concentration of LH in the serum. The well-known inhibitory influence of systemically administered melatonin on the accessory sex organs in male rats may be due to its antagonistic effect at a peripheral level.


Circadian variations in the plasma concentration of prolactin in the adult male rat. The occurrence of circadian variations in the concentration of prolactin in the plasma of 6- to 9-month-old male rats has been assessed in animals exposed to light for 14 h/day (lights on 06.00--20.00 h). Blood samples were obtained after decapitation, or from individual rats at regular intervals via a permanent cannula. Care was taken to limit stress during sampling. The concentration of prolactin in the plasma was significantly lower between 07.00 and 15.00 h than at other times. Between 15.00 and 20.00 h (during the light period), the concentration of prolactin was significantly higher in comparison with the preceding period, or with the remainder of the 24 h period. During the night, the concentration fluctuated, probably because of episodic releases of the hormone. The possible physiological significance of a circadian rhythm in the plasma concentration of prolactin and the implications for endocrine experimentation are discussed briefly.