A critical comparison of the value of pregnancy-associated alpha2-glycoprotein and carcinoembryonic antigen assays in patients with colorectal cancer. Absolute serum concentrations of pregnancy-associated alpha2-glycoprotein (alpha2-PAG) and carcinoembryonic antigen (CEA) were compared in 54 patients before and after surgery for colorectal cancer. Preoperatively, elevated levels of alpha2-PAG were found in 32 (59%) and of CEA in 35 (65%). Postoperatively, elevated alpha2-PAG levels were found in 10 of 18 patients (56%) without clinical evidence of recurrence whereas elevated CEA levels were present in three (16%). In patients who developed clinical evidence of tumour recurrence, alpha2-PAG levels were elevated in 8 of 13 (62%) while CEA levels were uniformly abnormal. It is concluded that, in this cross-sectional study, measurement of alpha2-PAG concentrations is less reliable than CEA in the detection of tumour recurrence after apparently curative surgery for colorectal cancer.


The location of spinal neurons with long descending axons (long descending propriospinal tract neurons) in the cat: a study with the horseradish peroxidase technique. The distribution spinal neurons with long descending axons was studied in the cat by means of retrograde transport of horseradish peroxidase. Labeled neurons appeared bilaterally in the cervical and the thoracic cord following injections in the lumbosacral cord. In some cases hemisections were made rostrally and contralaterally to the injections in an attempt to determine whether or not the axons crossed. Neurons with uncrossed descending axons were located in laminae I, V, VII and VIII. Lamina I neurons were present in all the spinal segments. In lamina V labeled neurons were distributed mainly laterally in the cervical cord but medially and laterally in the thoracic cord. In the upper cervical and the thoracic cord laminae VII and VIII neurons were distributed very densely along the lateral cord, accounting for 30 and 40 of the total labeled neurons, respectively. In the cervical enlargement they were located in the middle part of lamina VII and in lamina VIII, accounting for about 25% of the total labeled neurons. Neurons with crossed descending axons were found in laminae V, VII and VIII, in the medial part of lamina VII including the intermediomedial nucleus of the thoracic levels and close to the central canal. Lamina V neurons were very small in number. The largest collections of labeled neurons were present in the medial part of laminae VII and VIII. They accounted for about 45% to 55% and 37% of the total in the cervical and the thoracic cord. These neurons may function as the long spinal reflex paths for forelimb-hindlimb synergies and the intercalated paths between the supraspinal descending tracts and the spinal motor centers.


Anatomical organization of the spinocerebellar system in the cat, as studied by retrograde transport of horseradish peroxidase. The distribution of spinocerebellar tract (SCT) neurons has been studied in the entire length of the spinal cord of the cat following injections of horseradish peroxidase into the cerebellum, and whether or not the axons of the labeled neurons crossed within the spinal cord was determined in cases with injections preceded by hemisections at the cervical levels. The SCTs were classified into the following crossed and uncrossed tracts according to the cell origin and the fiber course; the crossed SCTs originate from (1) the central cervical nucleus (the CCN-SCT), (2) lamina VIII neurons of the cervical to the lumbar cord (the lamina VIII-SCT), (3) spinal border cells (the border cell-SCT), (4) neurons in the medial lamina VII of the lumbar to the caudal spinal segments (the medial lamina VII-SCT), (5) ventral horn neurons (laminae VII and VIII) of the sacral and caudal segments (the ventral horn-SCT) and (6) dorsal horn neurons (lamina V) of the sacral and the caudal segments (the dorsal horn-SCT). The uncrossed tracts originate from (1) neurons of the medial lamina VI of C2 to T1 (the medial lamina VI-SCT of the cervical cord), (2) neurons in the central part of lamina VII of C6 to T1 (the central lamina VII-SCT of the cervical enlargement), (3) lamina V neurons of the lower cervical to the lumbar cord (the lamina V-SCT), (4) Clarke's column (the Clarke's column-SCT and (5) neurons in the medial lamina VI of L5 and L6 (the medial lamina VI-SCT of the lumbar cord). The present study suggests that the spinocerebellar system originates from more diverse laminae than has previously been known, and further refined studies on the topographic projections of each tract will yield more important and valuable information in this field.


Structural and histochemical observations of fluorotic enamel matrix. The matrix of fluorotic enamel is studied by S.E.M. and histochemically by light microscopy. Observations are made on fluorotic human teeth and on rat incisors in which fluorosis has been produced by daily injections of NaF. The enamel sheaths appear enlarged and irregular, rich in stainable proteins, while glycocomponents of the matrix are less dense. A relationship is suggested between those alterations and the further irregular pattern of mineralization of fluorotic enamel.


A rapid ocular smear technique for optometrists: a preliminary report. The preliminary report discusses a clinical procedure in acquiring conjunctival smears, fixing the acquired sample and interpreting the results. Included is a description of the white blood cells frequently found in ocular smears and the clinical significance of each.


Biochemical relationship between murine immune interferon and a killer cell helper factor. Concanavalin A and alloantigen-stimulated mouse spleen cells release into the supernatant at least two distinct antigen-nonspecific factors that enhance the generation of cytotoxic cells in vitro. As previously reported, analysis of the supernatant by ammonium sulfate fractionation, gel filtration, hydroxylapatite chromatography, and hydrophobic chromatographic showed one of the two killer cell helper factors (KHF) to be associated with thymocyte mitogenic factor. This report demonstrates the second KHF to be separable from thymocyte mitogenic factor but inseparable from type II (immune) interferon. In addition, this KHF exhibits the same sensitivity to exposure to pH-2 buffer as does immune interferon. The KHF activity of an unfractionated supernatant, which is greater than of either the TMF-associated or interferon-associated KHF alone, is the result of the additive activities of the two independently acting helper factors.


Isolation of a type-specific antigen from Chlamydia trachomatis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. This report describes the isolation of a type-specific antigen of a serotype A strain of Chlamydia trachomatis. The antigen could be identified in sodium dodecyl sulfate-polyacrylamide electrophoretic (SDS-PAGE) analysis of immunoprecipitates of homologously reacted lysates from Bolton-Hunter 125I-labeled elementary bodies, solubilized by sonication and treatment with Nonidet P40. The electrophoretic pattern of this precipitate revealed a peak of unique mobility that was not reproduced by heterologous or control precipitates. Immunoadsorbtion of test antigen with purified IgG fractions from homologous antisera completely removed this peak, whereas similar adsorbtion wth heterologous IgG had minimal effect. Comparison of this antigen in SDS-PAGE with protein standards revealed an approximate m.w. of 27,000.


Suppressor cell induction in vitro. VI. Production of suppressor factors to synthetic polypeptides GAT and (T,G)-A--L from cells of responder and nonresponder mice. The capacity of responder and nonresponder strains of mice to generate suppressor cells and factors to two antigens under MHC linked Ir gene control was investigated. Eight different H-2 types (H-2b,d,f,k,p,q,r,s) as well as seven independently derived strains (B10, BALB/c, CBA/Ca, A/St, DBA/2, P/J, SJL) were tested, and all yielded suppressor factor (SF) to (T,G)-A--L and GAT. This indicated that the genetic control of SF production was different from that of helper cell induction. Unlike previous reports of GAT suppressor extracts that GAT-specific supressor factors acted equally on both responder and nonresponder strains. As reported earlier with in vitro induced protein- (KLH) specific suppressor factors, GAT and (T,G)-A--L specific suppressor factors failed to show any genetic restriction in their function. The implications of these results for the general mechanism of Ir gene control are discussed.


Characterization of the primary IgM response to GAT and GT: conditions required for the detection of IgM antibodies. Primary IgM antibody responses to synthetic linear copolymers of L-glutamic acid, L-tyrosine, and L-alanine were investigated. The appearance of primary IgM anti-GAT antibodies was detected in BALB/c mice by using a solid phase radioimmunoassay (SPRIA) procedure. The finding was verified for GAT in responder mice and GAT-MBSA and GT-MBSA in nonresponder mice in an indirect plaque forming cell (PFC) assay by using a rabbit antiserum directed against the mulambda myeloma protein, MOPC 104E. Facilitated IgM PFC could be inhibited by a purified muK myeloma protein, TEPC 183. Maximal facilitated IgM plaque response was found to precede the IgG response by several days. A direct plaque assay was developed for the detection of IgM anti-GAT plaques using poly-L-lysine (PLL) to couple GAT to sheep erythrocytes (SRBC). GAT-SRBC coupled by the PLL method optimally couple 4 to 5 times less antigen to the indicator cell surface than does the CrCl3-coupling method routinely employed in our laboratory. These findings were extended to a conventional antigen, chicken gamma globulin (CgammaG). We found that a less dense epitope coat on the indicator cell surface favors detection of direct IgM PFC, whereas a more densely coated indicator cell favors the detection of facilitated IgM and IgG PFC responses.


Generation of cytolytic T lymphocytes in vitro. X. Induction of primary and secondary CTL responses by the mitogen sodium periodate. Short-term (15 min) sodium periodate (NaIO4) treatment of mouse spleen cells previously primed in vivo or in vitro against alloantigens induced the formation of secondary (2 degree) cytolytic T lymphocytes (CTL) specific for the priming antigens. CTL formation was readily demonstrable within 24 hr after treatment. This early CTL response occurred equally well in the presence or absence of cytosine arabinoside (Ara C), indicating that NaIO4 could induce CTL independently of DNA synthesis. Forty-eight hours after periodate treatment, the lytic activity was similar to that observed in parallel cultures stimulated with irradiated allogeneic spleen cells, although the peak activity was reached earlier (day 4) and was somewhat lower than that induced by alloantigen. The addition of irradiated NaIO4-treated unprimed syngeneic spleen cells to cultures of untreated alloimmune spleen cells also led to CTL formation, which suggests an indirect mechanism of activation. In contrast to alloimmune spleen cells, normal spleen cells treated with NaIO4 developed only very low levels of cytotoxicity after 4 days of incubation. However, in the presence of PHA, such cells were capable of lysing syngeneic and allogeneic target cells.


Adoptive transfer of experimental allergic encephalomyelitis: incubation of rat spleen cells with specific antigen. Spleen cells from myelin basic protein (BP)-sensitized donor rats appear to be incapable of adoptively transferring experimental allergic encephalomyelitis (EAE) directly to normal recipients. It has been reported that in vitro incubation with concanavalin A (Con A) activates rat spleen cells so that they are capable of transferring EAE. We report here that incubation with specific antigen, BP, also permits transfer of disease with spleen cells. Data are presented in which activation of EAE spleen cells by Con A is compared with activation by BP. Cellular proliferation does not appear to be necessary for in vitro activation with specific antigen.


In vitro studies of antigen-induced bronchospasm: effect of antihistamine and SRS-A antagonist on response of sensitized guinea pig and human airways to antigen. Exposure of sensitized guinea pig tracheal rings or human bronchial strips to specific antigen in vitro resulted in a rapidly developing, prolonged contraction that was resistant to washing. Treatment of the tissue with diphenhydramine, a histamine H1 antagonist, before antigen delayed the onset and decreased the amplitude of the initial phase of the contraction but did not reduce the duration. Diphenhydramine treatment after development of the contraction did not relax the airway tissue. Antigen-induced histamine release from guinea pig trachea and from human bronchus was complete within the initial 15% of the duration of the contraction. Treatment of sensitized airway tissue with FPL 55712, a SRS-A antagonist, before antigen selectively inhibited the prolonged phase of the response. FPL 55712 administration after the development of antigen-induced contraction resulted in relaxation. These data suggest that both histamine and SRS-A are involved in the response of sensitized guinea pig and human airway tissue to antigen, with histamine mediating the early phase of the contraction and SRS-A primarily mediating the protracted phase.


F1 hybrid anti-parental H-2k cell-mediated lympholysis. I. Stimulator and target determinants controlled by the H-2K region. H-2k-heterozygous F1 hybrid mouse spleen cells cultured with irradiated H-2k-homozygous stimulator cells generated specific anti-parent cytolytic effectors. The parental antigenic determinants recognized by responder cells during induction (afferent arm) and by effector cells during cytolysis (efferent arm) were coded for, or regulated by, the H-2K-Hh3 region of the MHC, according to recombinant analysis. There were no detectable influences by other linked or unlinked genes on the phenotypic expression of parental antigens; however, the anti-parent responsiveness was modulated by background genes of responder cells. These experiments establish that the K end of H-2 controls determinants of F1 anti-parental H-2k CML, like the D end controls those of F1 anti-parental H-2b CML, thus confirming the basic symmetry of the H-2 complex. The relationship of this primary in vitro cell-mediated response with natural in vivo resistance to parental and allogeneic bone marrow grafts is discussed.


Virus specificity of human influenza virus-immune cytotoxic T cells. The virus specificity of human in vitro cytotoxic T cell responses to influenza virus was studied with the use of peripheral blood mononuclear leukocytes from normal adult volunteers. Previous natural exposure of these donors to a variety of type A influenza viruses was documented by HI antibody titers. Cells sensitized in vitro with A/HK or A/PR8 were cytotoxic for autologous target cells infected with A/HK, A/PR8, or A/JAP 305 type A influenza viruses, but not for B/HK-infected or uninfected cells. B/HK-sensitized effector cells lysed target cells infected with B/HK but not targets infected with type A viruses. A/HK- and A/PR8-immune effector populations were shown to recognize cross-reactive antigens on A/HK- and A/PR8-infected target cells by cold target competition. Influenza-immune effector cells were cytotoxic for virus-infected autologous targets but much less so for virus-infected allogeneic targets. This self-restriction suggested that the cytotoxicity was largely T cell-mediated and was confirmed by cell separation analysis. Thus, the human secondary cytotoxic T cell response in vitro to influenza viruses is predominantly directed against cross-reactive determinants on cells infected with serologically distinct type A influenza viruses.


[3H]Uridine uptake by target monolayers as a terminal label in an in vitro cell-mediated cytotoxicity assay. A terminal labelling method is described for measuring cell-mediated cytotoxicity based on the ability of surviving target cells to incorporate [3H]uridine into their RNA precursor pools. Parameters of the system were examined using whole and damaged embryonic mouse fibroblast monolayers. This assay is less laborious than direct cell counting and gives increased sensitivity at low target to effector cell ratios. The labelling time is short and, unlike similar techniques, it allows target cell monolayers to remain intact after completion of the radioassay and available for histological examination. This is important where heterogeneous target populations are employed since it allows assessment of differential cell killing and eliminates the need for duplicate cultures. The assay was used in conjunction with a well defined mouse popliteal lymph node assay to investigate the appearance of cytotoxic cells during a localised graft versus host response. Results showed a direct correlation between proliferative index and the development of highly specific cell-mediated cytotoxicity.


Identification of a subspecies-specific capsular antigen from Bacteroides melaninogenicus subspecies asaccharolyticus by immunofluorescence and electron microscopy. An indirect fluorescent antibody test was developed with the use of hyperimmune rabbit antiserum to a purified capsular polysaccharide of Bacteroides melaninogenicus subspecies asaccharolyticus. All of 23 strains of B. melaninogenicus subspecies asaccharolyticus were fluorescence-positive in this test. All 11 strains of Bacteroides melaninogenicus subspecies intermedius tested and three strains of Bacteroides melaninogenicus subspecies melaninogenicus were fluorescence-negative. Thirty-one strains of other bacterial species were also fluorescence-negative. The indirect fluorescent antibody test demonstrated the presence of a subspecies-specific capsular antigen from B. melaninogenicus subspecies asaccharolyticus. The capsular antigen was further demonstrated by electron microscopy with ruthenium red, a polysaccharide-staining material.


Early detection of aminoglycoside nephrotoxicity with urinary beta-2-microglobulin. We used a radioimmunoassay to evaluate the changes in the urinary excretion of beta2-microglobulin (beta2M) in 21 patients receiving aminoglycosides for treatment of infection. Excretion of this protein rose to a peak at least 5 times the baseline value in the urine, and declined rapidly to control values after drug administration ceased. In six patients who developed aminoglycoside nephrotoxicity, urinary beta2M excretion rose 5 days or more before serum creatinine rose, and 5 of 6 nephrotoxic patients excreted more than 50 mg/day (normal, less than 0.1 mg/day). Urinary beta2M is a non-specific indication of renal tubular damage, but heralds aminoglycoside-induced damage before standard tests of kidney function change.


Regulatory mechanisms in cell-mediated immune responses. VII. Presence of I-C subregion determinants on mixed leukocyte reaction suppressor factor. The presence of H-2 gene products on mixed leukocyte reaction (MLR) supressor factor was investigated by passage of MLR-suppressor factor (SF) over solid immunoadsorbents prepared with various anti-H-2 subregion sera. Antisera with specificity for all or certain I subregion determinants removed or significantly reduced suppressor activity; adsorption was not consistent with K or D region specificity. The single I subregion specificity common to all adsorbing preparations was I-C. Serologic differentiation of I-C products of k and d haplotypes expressed on MLR-SF was established with antisera prepared in I-Cd/I-Ck disparate strain combinations. These sera define allelic T cell restricted Lad determinants encoded by I-C genes. MLR-SF prepared from (BALB/c X CBA)F1 mice and exposed to the I-Cd and I-Ck specific adsorbents demonstrated d and k haplotype specific adsorption respectively. F1 suppressor activity adsorbed on an anti-I-Cd column was eluted by glycine-HCl buffer and suppressed only BALB/c (H-2d) responses. B10.A suppressor activity was removed by anti-I-Cd sera, but was unaffected by anti-I-Ck sera, indicating that B10.A suppressor activity is encoded by an I-C subregion derived from the d haplotype. Antisera with anti-I-Jk specificity did not remove suppressor activity of various H-2k factors. Finally, adsorption with antisera directed against H-2-associated determinants of the allogeneic cell used to stimulate suppressor factor generation demonstrated that sensitizing alloantigens are not components of MLR suppressor factor. Thus among the major histocompatibility complex (MHC)-controlled suppressor factors, MLR suppressor factor is uniquely determined by the I-C subregion.


Human macromolecular insoluble cold globulin (MICG). I. T-cell origin of T-MICG and null cell origin of N-MICG. Although surface immunoglobulin characterizes B cells in man, there are few surface markers that distinguish T cells. We have described a new protein synthesized in human T cells, termed T-MICG. This protein is a macromolecule of 225,000 daltons, is insoluble in the cold, and migrates as a beta-globulin on electrophoresis. Separation of human peripheral blood lymphocytes into T and B-cell populations by rosette sedimentation and anti-human-Fab columns clearly demonstrated the T-cell origin of the 225,000 dalton component. Furthermore, null cells were shown to synthesize a protein of 185,000 daltons, termed N-MICG, with physical properties similar to T-MICG, T-MICG and N-MICG were shown to be antigenically dissimilar, employing antiserum to each of these proteins. The present studies demonstrate two novel cell surface markers, T-MICG and N-MICG, which characterize T cells and null cells, respectively.


Immunodeterminant specificity of human immunity to type III group B streptococcus. The type III polysaccharides of group B Streptococcus in its native state chemically consists of glucose, galactose, glucosamine, and sialic acid. The core of this polysaccharide lacks sialic acid and precipitates with type III antiserum to give a partial identity with the precipitate between the native antigen and this serum. The core determinant is immunochemically similar to the capsular polysaccharide of type XIV Streptococcus pneumoniae, while the native type III group B streptococcal polysaccharide does not cross-react with type XIV pneumococcal antiserum. In human sera, it is antibody directed to the native antigen which correlates very highly with opsonic immunity (r = 0.94) while a poorer correlation exists between antibody to the core antigen and opsonins (r = 0.51 P less than 0.001). In natural infections, as association exists between low levels of maternal antibody to the native antigen and risk of disease in the infant. This association is not true for antibody to the core structure, where both infected infants and their mothers have much higher levels of antibody to the core than the native antigens. Infected infants are also more likely to respond to infection by developing antibody to the native antigen. Immunization of 12 adults with multivalent pneumococcal polysaccharide induced significantly better antibody response to the core antigen than to the native, and this vaccine induced opsonic activity in only one recipient. Immunization of adults with type III group B streptococcal antigens induced antibody to the native determinant which correlated with opsonic activity. Therefore, it would appear that native group B streptococcal polysaccharides will provide the best candidate antigens for immunization.


Testing of twenty-one environmental aromatic amines or derivatives for long-term toxicity or carcinogenicity. Twenty-one aromatic amines or derivatives were tested for long-term toxicity by dietary administration to male Charles River rats and male and female HaM/lCR mice. 2,4-Toluenediamine, o-phenylenediamine, o-toluidine, 2,4,6-trimethylaniline, 2,4,5-trimethylaniline, 2,5-xylidine, and 1-chloro-2-nitrobenzene led to tumors in one or more tissues in all three of these animal models. p-Toluidine, 4-chloro-o-toluidine and 1-chloro-4-nitrobenzene had varying degrees of activity, but in male and female mice only. 4-Chloro-4'-aminodiphenyl ether affected male rats and female mice, but there was no consistent dose response. 2,5-Dimethoxy-4'-aminostilbene led to many tumors in male rats but had only a questionable action in male mice. The effect of 3,3',4,4'tetra-aminobiphenyl in male rats was borderline; in the mice only males showed any response. In male mice 2,4,6-trichloroaniline had a fair degree of activity; tetrafluoro-m-phenylenediamine was somewhat less effective and m-toluidine had only questionable activity. 2,4-Xylidine increased lung tumors in female mice at the higher dose only. Four inactive compounds included m-phenyl-enediamine, 2,4-dinitrochlorobenzene, benzoguanamine, and dicyclopentadiene dioxide. 2,4,6-Trimethylaniline led to cirrhosis of the liver in rats only.


Immunological properties of conjugates of ragweed pollen antigen E with methoxypolyethylene glycol or a copolymer of D-glutamic acid and D-lysine. The major allergen of ragweed pollen, antigen E, was modified by coupling its amino acid groups with either methanol, methoxypolyethylene glycol (MPEG) of 5,000 daltons, or a synthetic copolymer of D-glutamic acid and D-lysine (DGL) of 34,000 daltons, all appropriately activated. The conjugates were characterized chemically and immunologically. Compared to the native antigen, the methoxy conjugate showed little reduction in allergenic activity, but the other two conjugates showed strong reductions, as measured by heterologous passive cutaneous anaphylaxis in rats sensitized with murine anti-antigen E reaginic sera. The MPEG conjugate was apparently nonimmunogenic in mice known to be high responders to the native antigen. MPEG and DGL conjugates retained the immunosuppressive property of the native antigen as subcutaneous treatment of antigen E sensitized mice with these two conjugates led to significant long-lasting depression of their antigen E-specific IgE and IgG antibody levels. These immunological changes are believed to result from reduction of antigenic valency and specificity upon coupling the bulky molecules to the protein antigens.


Lymphocyte specificity to protein antigens. II. Fine specificity of T-cell activation with cytochrome c and derived peptides as antigenic probes. Murine T-lymphocyte specificity was determined in a system of antigen driven in vitro T-cell proliferation using cytochrome c molecules from different species, their derived peptides and reconstituted hybrid proteins. It was observed that primed T cells could discriminate between peptide fragments which differed from each other at a single amino acid residue. These conclusions were substantiated by the pattern of cross-reactivity noted in the response of closely related cytochrome c proteins as well as when artificial hybrid molecules reconstituted by the covalent linkage of peptide fragments were analyzed. The pattern of specificity observed appeared to be haplotype (BDF1) dependent although similar conclusions about the fine specificity of T cells in the response to cytochrome c have been obtained in other strains but associated with different residues.


HLA-D region-associated determinants serve as targets for human cell-mediated lysis. Effector cells for cell-mediated lysis (CML) were generated by in vitro culture of lymphocytes from selected donors with X-irradiated cells from unrelated subjects who were HLA-D homozygous and matched to the responders for the antigens of the HLA-A and HLA-B regions. By using chromium labeled monocytes as target cells, cytotoxicity was found to correlate with presence of HLA-D region antigens matching those of the stimulating cells. Such CML reactions apparently directed at products of HLA-D, were inhibited by addition of unlabeled monocytes or B lymphocytes. These unlabeled cells had to be matched for HLA-D with the stimulating cells used to generate the effector populations. The results suggested that products of HLA-D, perhaps the DR antigens, were recognized by cytotoxic lymphocytes.


Role of a nonimmunoglobulin cell surface determinant in the activation of B lymphocytes by thymus-independent antigens. Lyb 5 is a B-cell alloantigen which is expressed on 50-60% of B cells. It was defined originally on the basis of cytotoxicity. We have described a new reactivity within the anti-Lyb 5 serum on the basis of selective inhibition of antibody responses in vitro by this antiserum in the absence of complement. This inhibitory activity of anti-Lyb 5.1 serum appears to be due to recognition of antigenic determinants different from the prototype antigens detected in the cytotoxicity assay. Anti-Lyb 5 serum incorporated into spleen cell cultures selectively inhibits antibody responses to a class of thymus-independent antigens (TI-2) previously characterized by their failure to elicit antibody formation in immature mice or in the defective CBA/N strain. Responses to optimal concentrations of TI-1 antigens, which can induce antibody synthesis in these mice, are unaffected by the addition of anti-Lyb 5.1 serum. The B-cell alloantigen defined by this functional assay is designated tentatively Lyb 7 and it is shown to be distinct from cell surface immunoglobulins. Lyb 7 appears to have a role in the activation of B lymphocytes by the TI-2 class of thymus-independent antigens.


Reduced lectin stimulation of lymphocytes from magnesium-deficient rats. Spleen cells and thymocytes from Mg-deficient rats, fed a Mg-deficient diet for 10--13 weeks, incorporate [3H]thymidine at half the rate of normal cells. The cells from Mg-deficient rats are less stimulated by lectins than those from normal animals. These effects correspond to the reduced content of gamma-globulins in serum in Mg deficiency. They are caused by the altered electrolyte content of the Mg-deficient cells.


A difference between the proteins conveyed in the fast component of axonal transport in guinea pig hypoglossal and vagus motor neurons. We compared the proteins transported in the fast component of guinea pig hypoglossal motor neurons with those of guinea pig vagus (preganglionic parasympathetic) neurons. The fast component proteins of hypoglossal and vagus neurons were radioactively labeled by injecting 3H-amino acids into the hypoglossal and vagus motor nuclei. The radioactive fast component proteins obtained from each system were then compared with each other by SDS-polyacrylamide slab gel electrophoresis and fluorography. These analyses revealed at least twenty polypeptides which appear common to the fast component of each neuronal system. In addition, we identified one difference between the proteins comprising the fast component of these neuronal systems. A polypeptide, molecular weight 50,000 daltons, present in the fast component of vagus neurons was not detected in the fast component of hypoglossal motor neurons. These observations are discussed with regard to the similarities and differences between these neuronal systems.


Effect of experimental colchicine encephalopathy on brain protein synthesis and tubulin metabolism. Colchicine blocks axoplasmic flow and produces neurofibrillary degeneration. Brain slices from mice injected intracerebrally with colchicine incorporated more [14C]leucine into protein and had a decreased uptake of [14C]leucine into the perchloric acid-soluble pool than did their controls. Brain RNA content was decreased and free leucine increased by colchicine-induced encephalopathy. The specific activities of proteins from subcellular fractions of colchicine-injected brain were increased in the nuclear fraction, the 100,000-g supernatant, and its vinblastine-precipitable tubulin. The ratio of the specific activity of the crude mitochondrial fraction to that of the total homogenate was decreased, as would be consistent with impaired movement of newly labeled protein into synaptosomes. Colchicine-injected brain extracts contained one or more cytosol fractions that stimulated ribosomal incorporation of [14C]leucine into protein in a cell-free system. Colchicine-binding-activity measurements indicated loss of soluble and particulate tubulin in colchicine-injected brains; the decrease of soluble tubulin was verified by its selective precipitation with vinblastine. Colchicine encephalopathy did not affect the rate of spontaneous breakdown of in vitro colchicine binding activity. Similarities of colchicine encephalopathy to the neuron's response to axonal damage suggest that colchicine-induced increase in protein synthesis may, in part, reflect a neuronal response to blockage of neuroplasmic transport.


Routing of transported materials in the dorsal root and nerve fiber branches of the dorsal root ganglion. After injection of the L7 dorsal root ganglion with 3H-leucine, fast axoplasmic transport carries some 3--5 x more labeled materials down the sensory fibers branches entering the sciatic nerve as compared to the dorsal root fiber branches of the neurons. Freeze-substitution preparations taken from the two sides of the lumbar seventh dorsal root ganglia of cats and monkeys showed little difference in the histograms of nerve fiber diameters of the sensory nerve fiber branch of these neurons as compared to the dorsal root fiber branches. A similar density of microtubules and of neurofilaments in the dorsal root and sensory nerve fiber branches over a wide range of fiber diameters was found in electron micrograph preparations. In the absence of an anatomical difference in the fibers to account for the asymmetrical outflow, a functional explanation based on the transport filament model was advanced.


Antibodies to galactocerebroside bind to oligodendroglia in suspension culture. Antisera raised in rabbits against galactocerebroside bind to bovine oligodendroglia in suspension in significant titer as demonstrated by indirect immunofluorescence. Absorption of antigalactocerebroside antiserum with galactocerebroside, oligodendroglia, or myelin markedly reduces the antigalactocerebroside antibody titer as measured by a radioimmunoprecipitation test as well as the binding to oligodendroglia. Incubation with  some other galactose-containing glycolipids results in a parallel decrease in binding to oligodendroglia and reduction in antigalactocerebroside antibody titer. Antigalactocerebroside antibodies provide a useful and specific tool with which to study development of oligodendroglia and myelin as well as immunopathologic mechanisms which might be involved in demyelinating diseases.


Modifications of the cerebrospinal fluid IgG concentrations in patients with multiple sclerosis treated with intrathecal steroids. Forty-one patients with multiple sclerosis (MS), in the acute exacerbation phase of the disease, were treated with three or four intrathecal injections of triamcinolone retard, 40 mg. Cerebrospinal fluid (CSF) specimens were collected at the first and at the last lumbar puncture, and analyzed for IgG and Albumin. There was a decrease of CSF IgG concentration in the specimens of 85% of the cases which were collected at the last lumbar puncture, compared to the initial concentration. Similarly, the CSF IgG/albumin ratio in the last specimens collected were reduced in 78% of the cases. Both these results are statistically significant.


The effect of arterial hypertension of focal ischemic edema. An experimental study. The middle cerebral artery (MCA) of cats was occluded permanently for 24h to study the influence of arterial hypertension during the early phase of focal ischemia upon the development of endema and changes of the blood-brain barrier (BBB). In normotensive animals MCA occlusion results in a hemispheric weight increase of about 8% and marked water and electrolyte alterations in both the grey and white matter of the MCA territory. The RISA space increases mainly in the grey matter. Hypertension aggravates these changes significantly, whereby water and electrolyte changes in the grey matter are predominantly concerned, while there is a preferential increase of the RISA space in the white matter. It is suggested that arterial hypertension aggravates the ischemic edema and enhances a vasogenic type of edema in the white matter.


Klinefelter syndrome and neurological disease. Six patients with Klinefelter syndrome (47,XXY) and different neurological disease are described. Essential tremor has been reported repeatedly but its significance deserves further studies. The prevalence of epilepsy with the Klinefelter syndrome is higher in comparison with the normal poplation, but it is not greater than expected in the population of a mental hospital. Therefore we suggest that the neurological symptoms with the Klinefelter syndrome should basically be regarded as coincidental findings not related to the chromosome abnormality.


Biochemical and immunological studies with human optic and olfactory tracts. Clinical and pathological studies have revealed that in multiple sclerosis (MS) the involvement of the optic tracts is much more frequent than that of the olfactory tracts. To investigate the possible reasons for this difference in involvement of these two adjacent structures, both containing a central type myelin, we have studied optic and olfactory tracts obtained at autopsy from 7 adult males ranging in age from 54 to 64 years. White matter from the frontal poles of the same individuals was used for reference. These tissues were compared with respect to the relative content of a) water, b) soluble proteins, c) 2',3'-cyclic nucleotide 3'-phosphohydrolase (CNP) activity, and d) immunologically precipitable basic protein (BP). Homogenates from these tissues were further compared by disc gel electrophoresis in two systems; phenolformic acid-water and SDS-urea gels. Results indicate that while the optic tracts and the frontal pole white matter were similar with respect to their water, total protein content and BP content, the optic tracts had lower CNP activity than the frontal poles. The olfactory tracts contained more water and less BP and the CNP activity of these structures was lower than that of the frontal pole white matter. Assuming the CNP activity and the BP content are true measures of the total myelin content of a given tissue, it appears that olfactory tracts have smaller amounts of myelin. On the other hand, the optic tracts contain only half as much CNP-activity with a disproportionately greater amount of BP. The possible significance of these findings is discussed.


Histochemical study of the muscle spindles in parkinsonism, motor neuron disease and myasthenia. An examination of the pathological fusimotor endings by the acetylcholinesterase technic. Pathological changes of the fusimotor endings in parkinsonism, motor neuron disease and myasthenia were examined by the acetylcholinesterase technic on serial sections. In parkinsonism, the diffuse endings, which are thought to be supplied by the static gamma nerve fibers, showed remarkable enlargement, while en plaque and en grappe endings were atrophic. In motor neuron disease, en plaque and en grappe endings, which are thought to be innervated by the beta nerve fibers and dynamic gamma nerve fibers respectively, revealed marked atrophy. However the diffuse endings were normal. In myasthenia gravis and myasthenic syndrome (Eaton-Lambert syndrome), en plaque and en grappe endings were atrophic, though only the diffuse endings were spared. The significance of these changes in the fusimotor endings is discussed.


Somatosensory evoked response in controlled A-alpha sensory fiber disease. In contrast to the distal sensory response, the somatosensory evoked response (SSER) is detectable in patients with A-alpha sensory fiber diseases such as Friedreich's ataxia. In four patients with this disease a combined histological and electro-physiological investigation of sensory propagation was performed. The sural nerve was analyzed in terms of the various fiber diameters and the distal sensory and somatosensory evoked cortical responses recorded after sural and median nerve (finger) stimulation. A distinct evoked response could be detected with rather low amplitudes and retarded latency times, while in general no distal sensory response was found. The anatomical physiological consequences are discussed.


Fenoterol precipitating myotonia in a minimally affected case of recessive myotonia congenita. Fenoterol is used in patients with premature labor to delay delivery. A young women treated with fenoterol developed severe generalized myotonia. Symptoms disappeared after medication had  been stopped. In a later study myotonic discharges were found electromyographically in the muscles of the patient and her brother. Both suffered from subclinical recessive myotonia congenita (Becker). A heterozygous manifestation may be supposed.


Serotonin metabolism with idiopathic grand mal seizures. Serotonin was determined in platelets of 140 patients with idiopathic mal seizures. According to anticonvulsive therapy these patients were divided into the following five groups: no medication, Diphenylhydantoin, Diphenylhydantoin calcium, Primidon, and combination of various of the anticonvulsants mentioned. The results obtained in the entire group of patients as well as in the various subgroups were compared with those of a group of healthy persons without therapy. In addition the various subgroups were compared to each other. There were significantly reduced serotonin values in the patients with idiopathic grand mal seizures as well as in each of its various groups as compared with the values obtained in healthy persons. Furthermore, significantly higher values were observed in the patients receiving primidone as compared with those receiving no anticonvulsants, Diphenylhydantoin, and a combination of various anticonvulsants. Our results taken together with those reported in the literature point to the possibility that a special imbalance in the cerebral neurotransmitter system, including a deficiency of serotonin, may represent a pathogenetic factor for idiopathic grand mal seizures. In addition, this investigation indicates that primidone elevates serotonin in platelets of patients with grand mal seizures.


Attempts to reproduce amyotrophic lateral sclerosis in laboratory animals by inoculation of Schu virus isolated from a patient with apparent amyotrophic lateral sclerosis. A virus isolated from the CSF of a patient who had amyotrophic lateral sclerosis for 7 years, and prolonged pleocytosis in the CSF, was adapted to suckling mouse brain by subsequent serial blind passages. This Schu virus belongs to the tick-borne encephalitis complex of the genus Flavivirus (Togaviridae). Suckling mouse brain homogenate of the 13th passage was used for transmission experiments in various species of laboratory animals. Golden hamsters infected subcutaneously fell ill after a number of months, lost weight, and had paresis of the legs. Histologically they had petechial hemorrhages in different parts of the CNS and inflammatory changes in the gray substance of the spinal cord. Pilot studies with repeated inoculations of small doses of different flavivirus strains suggest a course of the disease in experimental animals which resembles slow-virus infections insofar as no encephalitis is produced and degenerative changes of the anterior horn cells prevail over inflammatory signs in the spinal cord. After intracerebral application of Schu virus, cynomolgus monkeys developed the typical lesions of togavirus panencephalitis with epileptic seizures, ataxia, and paresis. After subcutaneous application, the virus seems to spread along peripheral nerves to anterior spinal roots and spinal cord, where mainly motor neurons of the anterior horn are damaged, and from there to the brain. The histological findings are such that one may assume the disease of the patient was due to the infection with the virus isolated from his CSF. Therefore, the hypothesis may be advanced that at least some of the cases diagnosed as amyotrophic lateral sclerosis are due to a togavirus infection.


Assessment of the value of thymic scan in myasthenia gravis. Fifty-three patients were investigated by Se methionine scan in order to evaluate the role of the thymus gland in myasthenia gravis. The thymus of 28 of the above patients was examined histologically. Five out of six thymomas were detected with this technique and eight out of twelve hyperplasias were revealed. The above data suggests that Se methionine scan is a useful, innocuous tool for diagnosing neoplasms and abnormal germinal centers in thymus glands.


Intramedullary spinal cord metastases.

Intramedullary spinal cord metastases. Seven autopsy cases of intramedullary metastases, four in the cervical spinal cord, are reported and the literature reviewed. Whereas lung and breast cancer, malignant melanomas and lymphomas are reported as the most common primary tumors, the present series included three cases of breast carcinoma and two cases each of colon and oat cell carcinoma of the lung. Neither the clinical symptoms nor the neurological signs distinguished intramedullary metastases from the more common extradural deposits, but radiological evidence of vertebral metastases and myelographic stop were present in only one case each, and CSF cytology was negative. Intramedullary deposits in this series were neither associated with extradural tumor nor with spread into the subarachnoid space, while cerebral metastases were present in four cases. This favors hematogenous dissemination rather than direct transdural or perineural spread of these lesions.


Recurrent familial neuropathy with liability to pressure palsies: reports of two cases and ultrastructural nerve study. Electrophysiological, histological and ultrastructural studies on two patients (one family) with familial neuropathy and a liability to pressure palsies are reported. There was slowing of nerve conduction velocities and increase of distal latencies of clinically affected and clinically non-affected nerves. These alterations were confirmed by biopsy of the sural nerive which had the characterized signs of the disease. Pathogenetically there seems to be an endogeneous metabolic defect of the Schwann cell to synthetize a normal myelin sheath, which is responsible for the particular susceptibility to mechanical damage.


Alternating myasthenia and myastheniform syndrome in the same subject. A man of 23 years was affected by myasthenia with amyotrophic patterns. From the neurophysiological viewpoint, there were typical electrophysiological aspects of myasthenia gravis and the Eaton-Lambert syndrome simultaneously. In some instances the various electrophysiological tests were preceeded by the administration of Tensilon, calcium gluconate and sodium benzoate caffeine. It is hypothesized that there are two types of endplates present, or there is a functional variability by which at different moments a block results from a defect in the formation or liberation of acetylcholine.


Microangiographic studies of denervated, reinnervated and hypertrophic muscles of rats. The behavior of the capillaries of denervated, reinnervated and hypertrophic muscle of rats was investigated with aid of microangiography. The vessels of the denervated muscle ran irregular, formed spirals and their parallel position to the muscle fibers was completely lost. The appearance of vessels after 3 and 6 weeks in the reinnervated muscle was similar to that observed after denervation. The pattern of vessels became more normal 3 months after the operation. The hypertrophic exercised muscles had an irregular course but with less tendency to spiral formation than atropic muscles. Their caliber was enlarged. The results showed that in denervated, reinnervated and hypertrophic muscle similar changes in capillary vessels develop. The vessels lose their parallel position to the muscle fibers and have a tendency to spiralization. The changes probably contributed to impairment of the circulation.


Egg counts utilizing trichrome-stained smears from polyvinyl alcohol (PVA)-preserved fecal specimens. A simple method of making egg counts on fecal specimens is described. It utilizes PVA-preserved stool, yields a permanent stained slide, and is as accurate and reproducible as other methods in common use.


Histochemical study of strain L fibroblasts exposed to endotoxin. The effect on cellular organelles. Endotoxin was found to be nonselective in its cytotoxicity of cellular organelles. All organelles studied displayed some degree of alteration which became more severe as the concentration of endotoxin was increased. The data suggest that the metabolism of the cell may be compromised at concentrations of endotoxin which do not affect cell viability. The problem involved in attempting to determine the actual concentration of endotoxin at the interface between the culture medium and the cell monolayer, in vitro, and the corresponding situation, in vivo, are also discussed.


Glycoproteins released by Leishmania donovani: immunologic relationships with host and bacterial antigens and preliminary biochemical analysis. The antigenically active glycoproteins (AAGP) released by Leishmania donovani strain 3S promatigotes into growth media and by amastigotes of this strain into the tissue, e.g. blood, of infected hamsters was found to consist of 6 to 7 antigenically distinct components. The antigenic activity of these glycoproteins was resistant to freeze-thawing, protease treatment, and purification by column chromatography using Sephadex G-100. This activity, however, was destroyed by Na periodate and altered by boiling; AAGP adhered firmly to Amicon filter (UM2). The antigenically active substances absorbed UV at 230, 260, 280 nm and gave positive Folin phenol, phenol sulfuric acid, and orcinol reactions. By gel diffusion, the component glycoproteins were found to form lines with concanavalin A and to give reactions to identity and partial identity with human red cells and Mycobacterium butyricum. The possible involvement of the antigenically active glycoproteins in pathogenesis of kala azar is discussed.


Small inclusions in the cytoplasm of leukocytes in LE cell tests. Small homogeneous basophilic and eosinophilic particles varying in size from 0.7 to 3.0 micra were seen in cytoplasm of monocytes and polymorphonuclear cells of leukocytes in LE cell tests. The aim of this investigation was to determine their frequency and diagnostic significance. Inclusions were found in one-third of LE cell tests on patients with rheumatic diseases and were not observed in normals. In 19.1% of 161 patients with SLE, they were present before LE cells were found. Sixty-eight% of patients who had particles had SLE, 8% had rheumatoid arthritis with LE cells, and 3% had nonrheumatic diseases.


Pediculosis ciliaris.

Pediculosis ciliaris. Pediculosis ciliaris, though not as common as in the past, is still not a rare disorder. Infestation has become more prevalent among adolescents within the past few years. Severe itching, irritation, secondary conjunctivitis, and preauricular adenopathy may accompany the louse infestation. A brief review of the etiology and treatment of pediculosis ciliaris has been presented. Every physician should be aware of this disorder and be adequately prepared to treat it.


The binding of anti-DNA antibodies as measured fluorometrically by ethidium bromide. The phenanthridine dye ethidium bromide (EB) intercalates with double-stranded DNA (dsDNA) resulting in an enhancement of fluorescence. Single-stranded DNA (ssDNA) does not show this fluorescent enhancement. Purified IgG from patients with Systemic Lupus Erythematosus (SLE) containing anti-dsDNA antibodies competes with EB for binding to DNA resulting in a decrease in fluorescence. This study has shown that antibodies which bind ssDNA in the Millipore filter radioimmunoassay displace EB from dsDNA showing that antigenic determinants are available for binding in the double-stranded molecule. This study introduces the EB assay and presents a comparison with the Millipore filter assay.


Management of a learning resource center: a seven-year study. Data compiled over seven years present evidence that small-group or "cluster" carrels are successfully utilized by medical students in a learning resource center (LRC) and, therefore, should be considered to be an efficient method of managing space, software, and hardware. Three management concepts account for high utilization of an LRC operated as a service in support of a medical school curriculum. Of special importance is the interaction of LRC staff with faculty, which directly accounts for a collection relevant to the curriculum. The other management concepts are responsiveness to students and delivery of services that support production and distribution of print and audiovisual resources for student learning.


Negative staining of freeze-fractured envelopes of Escherichia coli K12. Envelope fragments of E. coli K12 have been produced by freeze-fracturing "by hand" and negatively stained after thawing. The outer leaflet of the plasma membrane disintegrated upon thawing whereas the outer leaflet of the outer membrane did not. Negative staining revealed the following structural features on the outer membrane fragments: (i) "grooves" 4-6 nm wide, (ii) spherical particles 6-8 nm in diameter, (iii) "black dots" 3-8 nm in diameter. Treatment of cells with EDTA before freeze-fracturing caused dilation of grooves into holes eventually leading to fragmentation of the outer membrane. A mutant strain deficient in two outer membrane proteins fractured exclusively through the outer membrane. The outer leaflets so obtained disintegrated upon thawing similarly as observed for the outer leaflet of the plasma membrane.


The diagnosis of breast cancer by fine-needle aspiration smears. Forty-eight percent of 93 breast carcinomas that were aspirated with a fine needle were found to be cytologically positive for carcinoma, and in another 31% this diagnosis was suspected. Care of most breast cancer patients with abnormal or questionable aspiration smears was affected by cytological diagnosis. Thirty-seven patients with a positive diagnosis for carcinoma and with consistent clincal findings were informed of the diagnosis prior to surgery and underwent modified radical mastectomies without further frozen-section examination. Twelve other patients with suspect or abnormal cytological reports had biopsies performed earlier because of these findings. A cytopathological diagnosis of carcinoma based on aspiration smears of the breast is highly accurate if strict criterions of malignancy are applied, but normal smears from solid breast masses do not exclude malignancy.


Gc globulin and prealbumin serum levels in patients with cancer and benign inflammatory diseases and in asymptomatic smokers. Gc globulin and prealbumin serum levels were determined in a coded serum panel from the National Cancer Institute-Mayo Clinic. Serum samples came from 100 patients with cancer (lung, prostate gland, or gastrointestinal tract), from 50 patients with benign inflammatory diseases from the same organs as those of the cancer patients, and from 50 clinically healthy smokers. No differences were observed among groups in the Gc globulin (vitamin D carrier) serum concentrations; however, prealbumin (vitamin A carrier) serum levels were decreased for patients with benign inflammatory diseases and for cancer patients; the cancer group showed the greatest decrease.


Hepatitis B virus infection in southern African blacks with hepatocellular cancer. The association between hepatitis B virus (HBV) infection and hepatocellular cancer (HCC) in southern African blacks was investigated by examination of patients' sera for all the currently known markers of HBV. Hepatitis B surface antigen (HBsAg) was present in the sera of 61.6% (178/289) of the patients compared with only 11.3% (24/213) of age-matched, sex-matched, and ethnically matched controls (P less than 0.001). Antibody against HBsAg was found in 17% of the patients and 41.7% of the controls (P less than 0.001). In 74 patients studied in more detail, antibody against the hepatitis B core antigen (anti-HBc) was detected in 89%, almost always in high or moderately high titer. Anti-HBc was found in 37.5% of the controls. Active HBV infection, as indicated by positive tests for HBsAg or anti-HBc, was present in 91% of the patients compared with 39.4% of the controls (P less than 0.001). Hepatitis B e-antigen was detected in 2.3% and its specific antibody in 20.5% of the patients. The corresponding figures in the controls were 0 and 55%. HBs antigenemia was more common in younger patients with HCC. No relationship was demonstrated between alpha-fetoprotein and HBs antigenemia. HBV infection was equally common in patients with and without cirrhosis in the nontumorous liver.


Differences in cell surface antigens of tumor metastases and those of the local tumor. Tests were made to determine whether cell surface tumor antigens of metastases differed from the tumor antigens of the cell population of the local tumor growth. C57BL/6 mouse spleen lymphocytes sensitized against monolayers of the local growth of the 3LL Lewis lung carcinoma (L-3LL) in the presence of syngeneic serum generated lymphocytes that were cytotoxic to L-3LL but significantly less cytotoxic to target cells derived from lung metastases (M-3LL). Lymphocytes sensitized against M-3LL were significantly more cytotoxic against M-3LL than against L-3LL cells. Anti-M-3LL cytotoxic lymphocytes but not anti-L-3LL, admixed with either L-3LL cells or M-3LL tumor cells, when injected into syngeneic recipients reduced lung metastasis significantly. Results indicated that cells with high metastatic capacity and distinct antigenic properties exist within the tumor cell population and that immunoselection might be involved in the production of lung metastases.


Serologically defined, unique surface antigen on a mouse mammary adenocarcinoma. Syngeneic A.SW mice were immunized with sublethal viable cells of a spontaneous mammary adenocarcinoma S3W. The serum was tested by complement-dependent cytotoxicity against in vitro-cultured S3W cells and a spectrum of controls. S3W cells were found to react with at least four different kinds of antibodies in the serum. One antigen was present on several leukemia cell lines. A second cross-reactive antigen was detected on polyoma virus-induced tumors. A third was demonstrated on other mammary carcinoma lines and in a sarcoma of C3H origin. Following the removal of all three antibodies by absorption with the appropriate cross-reactive target cells, a fourth antibody remained that gave a strong cytotoxic reaction with S3W but with no other target line tested.


Natural polyclonality of spontaneous AKR leukemia and its consequences for so-called specific immunotherapy. Young female AKR mice made leukemic by iv inoculation of 10(3) spontaneous AKR thymoma cells were treated with repeated injections of irradiated cells from the same tumor. Treatment began 1 day after injection of the viable cells. The cytotoxicity of sera and lymphoid cells from healthy mice immunized with lymphoma cells from either treated or nontreated mice with leukemia grafts revealed that the tumor cells could be subdivided into four distinct antigenic types. One type (clone A) accounted for about 97% of the lymphoma cells in each mouse with spontaneous leukemia, whereas the remaining 3% were subdivided into three other distinct antigenic types (clones B, C, and D). Lymphoma cells from treated mice with grafted leukemia were never clone A type but either clone B, C, or D type. Repeated sc injections of 10(7) irradiated cells from spontaneous AKR thymomas induced from 15 to 34% cure in mice with grafts of leukemia cells. Treatment with only clone A induced about 32% cure, whereas treatment with clone B, C, or D had no beneficial effect. Treatment with 10(7) cells each of clone A plus clone B gave 33% cure; clone A plus clone B plus clone C, 45%; and all four clones cured 92% of the mice with leukemia grafts. The efficiency of immunotherapy may be influenced by the natural clonality of the tumor to be treated.


Deep hypothermic arrest: observations on later development in children. Thirty-two children were reviewed following closure of ventricular septal defect in infancy. Fifteen had undergone continuous perfusion and 17 had been subjected to core cooling followed by deep hypothermic arrest. Parental and professional evaluations of intellectual and motor development, at periods between 7 and 72 months following operation, suggest that there is a higher incidence of developmental abnormality in the subgroup treated with deep hypothermic arrest.


[Geometric phagedenism. Clinico-therapeutic experience]. A woman of 35 years old, in good physical condition, developed multiple lesions of Phagedenisme Geometrique (Pyoderma Gangrenosum) in the gluteal region and the thigh. Corticoids and antibiotics were used at high dosages resulting in healing of the center of the lesions but without any effect on the periphery. Plasma transfusions were then given, resulting in apparent amelioration of the peripheral abcesses. Her general condition was not altered during the entire course of the disease. Septic foci were not demonstrated and a minimal dysproteinemia was neither significant nor persistent.


Outcome of anorexia nervosa.

Outcome of anorexia nervosa. 100 females with anorexia nervosa were followed up 4-8 years after first presentation.  All but 12 had had refeeding and/or psychotherapy. 48 had a good outcome (weight at least near normal, regular menstruation, largely satisfactory mental state and psychosexual and psychosocial adjustments) but outcome was intermediate in 30, and poor in 20 patients. 2 had died. Poor outcome could be positively associated with clinical data such as longer duration of illness, older age of onset and presentation, lower weight during illness and at presentation, presence of symptoms such as bulimia, vomiting, and anxiety when eating with others, poor childhood social adjustment, and poor parental relationships.


Dietary carbohydrate and metabolism of ingested protein. Six normal people were fed a lean beef meal while on a normal diet and after seven days on a very low carbohydrate (greater than 25 g/day) 2000 kcal/day diet. After carbohydrate restriction, the protein-induced rise in branched chain aminoacids was 40-50% greater than the rise after the control diet. Intravenous leucine also produced a 40% greater rise in plasma-leucine after carbohydrate restriction. Three days of fasting exaggerated protein-induced increases in plasma branched-chain aminoacids by 55-77%. Hypocaloric, pure carbohydrate refeeding restored the branched-chain aminoacid responses to normal. Severe carbohydrate restriction thus leads to increased accumulation of plasma branched-chain aminoacids after protein feeding which is at least in part due to reduced utilisation of these aminoacids.


Glucose promotes whole-body protein synthesis from infused aminoacids in fasting man. Isotopic demonstration. 15N-glycine constant infusion, with plateau urea enrichment as the endpoint, demonstrated a clear increase in whole-body protein synthesis when glucose was added to aminoacid infusion in fasting men. Whole-body protein-breakdown rates remained unchanged. There was an unexpected fall in whole-body nitrogen turnover when the subjects were changed from an oral intake to either of the intravenous programmes: this finding, not previously reported, may be due to the decrease in gastrointestinal enzyme synthesis and intestinal-lining cell-turnover when oral intake is replaced by total parenteral nutrition.


High-density lipoprotein and coronary risk factors in normal men. Serum high-density-lipoprotein cholesterol (H.D.L.) was measured in 2568 men attending a screening centre and registered with a medical practitioner in Great Britain. Serum-total-cholesterol (T.C.), serum-triglyceride, serum-glucose, systolic and diastolic blood-pressures, electrocardiogram, chest X-ray, height, weight, cigarette and alcohol history, and a brief assessment of physical activity were also recorded. H.D.L. was inversely related to cigarette-smoking, relative weight, and serum-triglyceride level, and directly related to physical activity, total-cholesterol level, and alcohol consumption. The ratio of H.D.L. to T.C. (H.D.L./T.C.) showed similar significant relationships to the above variables (except that the ratio was negatively correlated with T.C.). In addition the ratio was inversely related to age. These relationships were independent of the other measured variables. Both the H.D.L. and H.D.L./T.C. were inversely related to coronary risk rating. It is suggested that, despite methodological problems, H.D.L. is a useful biochemical measurement to add to a coronary risk profile.


Immunoprecipitation and opsonic cross-reaction between type-14 pneumococcus and group-B streptococcus type III. Antisera directed against type-14 pneumococcus was opsonic for several strains of type-III group-B streptococcus. Furthermore, the polysaccharide antigen in the polyvalent pneumococcal vaccine reacted to form precipitation lines with antisera directed against type-14 pneumococcus and group-B streptococcus type III Immunisation with currently available pneumococcal vaccine may provide opsonic antibody against group-B streptococci and provide a method of preventing neonatal group-B streptococcal infections.


Effect of catecholamine replacement with levodopa on the metabolic response to semistarvation. The resting metabolic rate (R.M.R.) falls on energy restriction in association with a fall in the circulating calorigenic hormones, triiodothyronine (T3) and noradrenaline. Levodopa, a precursor of catecholamines, was given to obese subjects receiving a low-energy diet in an attempt to prevent the reduction in catecholamine turnover and noradrenaline levels. Levodopa prevented the fall in R.M.R. despite the expected decline in T3 levels on semistarvation. These results suggest that changes in catecholamine metabolism are important in determining adaptive changes in metabolic rate.


Social inequalities undiminished.

Social inequalities undiminished. Traditional differences in death-rates by social class continue in Britain in the 1970s, mostly at lower levels of mortality. The professions do well, unskilled workers and their families particularly badly. Data on health services are scanty, but they suggest that lower-class families, with greater needs, do not make proportionate demands on some services and receive less of others. Continuing socioeconomic inequalities, disparities in child health and education, and current smoking and exercise habits indicate that inequalities in health will persist. Some ways of levelling up are suggested, starting with children: by creating more equal opportunities for the under-5s through education and day care, expanding child benefit and family endowment, concentrating health services on the socially disadvantaged, and setting an upgraded "health education" to the task--with mothers and children and the whole population.


Neurosyphilis today.

Neurosyphilis today. 17 cases of recently diagnosed neurosyphilis are reviewed. The presenting features are diverse, and a clinical diagnosis may be difficult. Routine serological test are essential to confirm the clinical diagnosis.


Low-dose factor VIII in adults with haemophilic arthropathy. 27 adults with haemophilic arthropathy infused freeze-dried factor-VIII concentrate at a mean initial dose of 7.3 and 5.5 units/kg, respectively, during two successive 6-month periods of home therapy. A single infusion at either dosage level successfully terminated over 80% of bleeds. A 32% reduction in use of concentrate was achieved at the lower dose, with a cost saving equivalent to pounds 30 000 per annum and with no apparent short-term clinical disadvantage. Thus low-dose therapy can be successfully applied to severely affected adult patients with established haemophilic arthropathy.


Cervical ripening and induction of labour with intravaginal prostaglandin F2 alpha. A randomised double-blind trial was done to determine the effect on cervical ripening of 50 mg intravaginal prostaglandin F2 alpha (P.G.F.2 alpha) in a methyl cellulose gel given on the evening before surgical induction of labour. Patients were given either placebo or P.G.F.2 alpha and in both groups cervical stretching and sweeping of the fetal membranes was attempted. Of the 40 control patients, 3 had gone into labour and the mean improvement in the cervical score was 1.6 before surgical induction the next morning. However, 20 of the 40 patients receiving P.G.F.2 alpha went into labour before the proposed induction and the mean change in cervical score (5.1) was significantly greater than that in the placebo group. Of the 40 patients pretreated with P.G.F.2 alpha, 37 had improved cervical scores and significantly fewer required augmentation in labour with intravenous oxytocin than in the control group. No side-effects were experienced and the patients found the treatment acceptable.


Comparison of disodium cromoglycate and sulphasalazine as maintenance therapy for ulcerative colitis. In a trial lasting six months disodium cromoglycate (800 mg daily), sulphasalazine (2 g daily), and these two agents in combination were compared in 120 patients as maintenance treatment for ulcerative colitis. Relapse was defined as recurrence of colitic symptoms accompanied by sigmoidoscopic evidence of inflammation. The patients receiving disodium cromoglycate had a much higher relapse-rate than those taking sulphasalazine and the results with the two agents combined were little different from those with sulphasalazine alone. Disodium cromoglycate in the dose employed is greatly inferior to sulphasalazine as maintenance treatment for the prevention of relapse in ulcerative colitis.


"Insulin" allergy due to zinc.

"Insulin" allergy due to zinc. An investigation of two unrelated patients who had local cutaneous hypersensitivity reactions after injection of any commercially available insulin preparation has shown that the cause of the allergy was zinc. Zinc-insulin and zinc sulphate induced transformation and proliferation of peripheral-blood lymphocytes from these patients; they also induced the production of a specific leucocyte inhibitory factor. Intradermal skin-tests for zinc were positive in both patients. Similar studies carried out in a patient whose cutaneous allergy to insulin was corrected by changing from mixed beef-pork to pure pork insulin were negative. Zinc-free insulin did not produce any allergy in the first patients. The number of patients in whom zinc (which is present in all commercially available insulin preparations) is a cause of "insulin" allergy is unknown. These patients may by identified by intradermal skin-tests. This previously unrecognised allergy should be considered in all patients whose insulin allergy does not respond to conventional therapy.


Arginine therapy of argininosuccinase deficiency. Argininosuccinic acid (A.S.A.) contains the two waste nitrogen atoms later excreted in urea in healthy people, and it has a renal clearance similar to the glomerular filtration-rate. Therefore, argininosuccinic acid might provide a vehicle for the excretion of waste nigrogen in patients with argininosuccinase deficiency, providing that stoichiometric amounts of ornithine are available. When two infants with no, or very little, erythrocyte argininosuccinase activity who were in neonatal hyperammonaemic coma were treated with supplementary arginine (4-5 mmol/kg/day) plasma ammonium, glutamine, and alanine concentrations became normal. One infant grew and developed normally during the first month of life on a protein intake of 2 g/kg/day. The other infant had sustained lathal brain damage before arginine therapy was tried and she died aged 17 days. Arginine supplementation may be effective therapy for argininosuccinase deficiency because it promotes A.S.A. synthesis and hence excretion of waste nitrogen. The effects of high plasma-A.S.A. concentrations are unknown.


Growth-stimulating factor in regenerating canine liver. Extracts from dog livers which had been regenerating for 24, 48, and 72 h after hepatectomy were infused for 6 h into the left portal vein of animals which had fresh portacaval shunts (Eck fistula) and which were killed 2 and 3 days later. The brief exposure to the 48-h and especially the 72-h regenerating liver extracts induced a delayed proliferative response predominantly in the left liver lobes, with a slight spillover effect to the right liver lobes but none to the kidney. The response reached its peak 3 days later. In the left but not the right liver lobes, both the 48-h and the 72-h regenerating liver extract reversed the atrophy ordinarily caused by Eck fistula in 3 days and partly prevented the ultrastructural hepatocyte deterioration characteristic of Eck fistula. The active liver extracts apparently contained a growth-control factor or factors which is (are) not insulin or glucagon.


Survival of heart allografts in rats treated with azathioprine and sodium salicylate. In a rat heart transplant model representing a severe mismatch, median survival time (M.S.T.) with no treatment was 6 days. M.S.T. with azathioprine was 6 days, and with azathioprine and methylprednisolone 7 days. Azathioprine with promethazine hydrochloride gave an M.S.T. of 15 days. In rats treated with sodium salicylate alone M.S.T. was 16 days, and when azathioprine was administered for 12 days in a group continuously treated with sodium salicylate, all hearts were beating normally at 50 days.


Atypical phenylketonuria caused by 7, 8-dihydrobiopterin synthetase deficiency. A patient with atypical phenylketonuria and normal liver dihydropteridine reductase and phenylalanine-4-hydroxylase activities excreted neopterin but not biopterin or dihydrobiopterin in urine. The oral administration of L-sepiapterin (1 mg/kg body weight) lowered serum-henylalanine from 17.1 to 1.1 mg/dl within 6 h. Comparable responses were observed after oral administration of L-erythro-7, 8-dihydrobiopterin or L-erythro-5, 6, 7, 8-tetrahydrobiopterin (each given in a dose of 2.5 mg/kg body weight). The results indicate a 7, 8-dihydrobiopterin synthetase deficiency in the patient.


Haematin therapy and leucocyte delta-aminolevulinic-acid-synthase activity in prolonged attack of acute porphyria. The activity of leucocyte delta-aminolaevulinic-acid (A.L.A.) synthase was monitored throughout a prolonged attack of acute  intermittent porphyria in a 29-year-old women. Clinical severity was associated with a pronounced increase in activity of this enzyme and high urinary excretion of A.L.A. Haematin therapy resulted in clinical improvement associated with a reduction in the activity of A.L.A. synthase and reduction in urinary excretion of A.L.A.


Gestation, birth-weight, and spontaneous abortion in pregnancy  after induced abortion. Report of Collaborative Study by W.H.O. Task Force on Sequelae of Abortion. The outcome of pregnancy in 7228 women from eight European cities was studied. In two of the three city clusters, there was a significantly higher risk of adverse outcome in terms of either mid-trimester spontaneous abortion, preterm delivery, or low-birth-weight infant among women whose only previous pregnancy had been surgically terminated only previous pregnancy had been surgically terminated than among primigravidae or women whose only previous pregnancy had ended in live birth. In one city cluster in which surgical termination was accomplished both by conventional dilatation and currettage and by vacuum aspiration (V.A.), an increased risk of short gestation was noted for V.A., but the overall total risk of adverse outcome was not significantly increased. In the third city cluster, in which surgical termination was nearly entirely by V.A., induced abortion was not associated with any increased risk of adverse pregnancy outcome. The effects of spontaneous abortion on the subsequent pregnancy are similar to those of induced abortion.


Discrimination between iron-deficiency and heterozygous-thalassaemia syndromes in differential diagnosis of microcytosis. Three formulae have been advocated for interpreting the blood-count when differentiating between iron deficiency and heterozygous thalassaemia: the discriminant function. M.C.V.-R.B.C.-(5 X Hb)-k, the M.C.V/R.B.C. ratio, and the (M.C.V.)2 X M.C.H. product. In a comparison of their diagnostic accuracy in microcytic adults from several countries, the discriminant function was the most satisfactory. 417 of 455 uncomplicated cases (91.6%) of iron deficiency, heterozygous alpha1- and beta- thalassaemia were correctly identified. The function was not able to distinguish heterozygous alpha2-thalassaemia from iron deficiency. A flow chart illustrates how the discriminant function can be used in haematological practice.


A renal abnormality as a possible cause of "essential" hypertension. The renal abnormality which causes hypertension in the Milan hypertensive strain of rats disappears as hypertension develops. Because of the many analogies between the condition in these rats and "essential" hypertension in man, the same pattern of change may occur if a renal abnormality is the cause of essential hypertension in man. This hypothesis was tested in two groups of young normotensive subjects matched for age, sex, and body-surface area; in the first group both parents were hypertensive, and in the second group both parents were normotensive. Renal plasma-flow, glomerular filtration-rate, plasma-volume, plasma-renin activity, plasma-concentrations of Na+, K+, and catecholamines, 24 h urinary excretion of Na+, K+, and aldosterone, and the cardiac index were measured so that renal function and the role of factors affecting blood-pressure regulation could be assessed. Renal plasma-flow was significantly higher (p less than 0.01) in the first group, whereas results of tests for all the other factors were almost the same in both groups. The hypothesis that a primary kidney abnormality causes hypertension in a proportion of patients with essential hypertension is proposed.


Pharmacokinetic and clinical studies in patients with cimetidine-associated mental confusion. 15 cases of cimetidine-associated mental confusion have been reported. In order that this syndrome might be investigated changes in mental status (M.S.) were correlated with serum concentrations and renal and hepatic function in 36 patients, 30 patients had no M.S. change on cimetidine and 6 had moderate to severe changes. These 6 patients had both renal and liver dysfunction (P less than 0.05), as well as cimetidine trough-concentrations of more than 1.25 microgram/ml (P less than 0.05). The severity of M.S. changes increased as trough-concentrations rose, 5 patients had lumbar puncture. The cerebrospinal fluid: serum ratio of cimetidine concentrations was 0.24:1 and indicates that cimetidine passes the blood-brain barrier; it also raises the possibility that M.S. changes are due to blockade of histamine H2-receptors in the central nervous system. Patients likely to have both raised trough-concentrations and mental confusion are those with both severe renal and hepatic dysfunction. They should be closely observed and should be given reduced doses of cimetidine.


Seminiferous tubule hypercurvature: A newly recognised common syndrome of human male infertility. Testicular biopsy specimens from 42 of a series of 70 consecutive cases of primary male infertility and from 25 normal controls were morphometrically analysed. Although all the specimens from infertile males were normal by conventional histological standards, stereological measures of curvature in histological sections showed that cases of idiopathic male infertility had an abnormally increased curvature of seminiferous tubules.


Rationalisation of first-aid measures for elapid snakebite. The plasma of monkeys envenomated with tiger snake (Notechis scutatus) venom was monitored by radioimmunoassay for both crude venom and a neurotoxin. When the injected limb was immobilised and a pressure of 55 mm Hg applied to the injection site, only very low levels of circulating venom or neurotoxin were detectable. In practical terms, venom movement can be effectively delayed for long periods by the application of a firm crepe bandage to the length of the bitten limb combined with immobilisation by a splint. Pressure alone or immobilisation alone did not delay venom movement.


Aetiological relation between Korean haemorrhagic fever and nephropathia epidemica. A close aetiological relation between Korean haemorrhagic fever and nephropathia epidemica of Scandinavia has often been suggested because of similarities in their clinical picture and epidemiology. This relation has now been confirmed serologically; raised titres of antibody to Korean haemorrhagic fever agent and seroconversions have been found by the indirect fluorescent-antibody technique in 20 patients with nephropathia epidemica.


Application of ultrasound in assessing burn depth. Conventional pulse echo ultrasound equipment was modified to provide resolution capable of distinguishing the interfaces in burnt skin. The identification of these interfaces allowed a quantitative assessment of the depth of a burn. Ultrasound is non-invasive and accurate, and so is highly acceptable for clinical use.


Association between immunoglobulin allotypes and immune responses to Haemophilus influenzae and Meningococcus polysaccharides. Serum samples were collected from 20 healthy White and 33 Black infants before and after immunisation with three doses of diphtheria-pertussis-tetanus vaccine and with one dose of Haemophilus influenzae type b polyribose phosphate vaccine and meningococcal group A and group C polysaccharide vaccines. Antibodies to these immunogens were measured and sera were allotyped for several Gm, A2m, and Km antigens. A highly significant association was found between the Km(1) allotype and the immune responses (difference between post-immunisation and pre-immunisation antibody levels) to H. influenzae and meningococcus C polysaccharides in the White children.


Consumer survey on microbiology reports. 5 typical microbiology reports were circulated to the medical staff of a 900-bed teaching hospital and they were asked for their interpretations. Approximately 160 completed replies were received and it was clear that the reports were often misinterpreted; one report (isolation of a gram-negative rod from sputum) was misinterpreted by four doctors out of five. The reasons for this failure of communication seem to be the use of jargon and unfamiliar names of bacterial species, and use of ill-defined reporting conventions. The omission of a clear-cut conclusion from many reports also contributed to misunderstanding. These deficiencies in reporting practices result in unnecessary antibiotic therapy and unnecessary work for the laboratory, since clinicians are more likely to ask for a repeat of a test with a doubtful interpretation. Communications with clinicians would be more effective if microbiologists ensured that each report is free of jargon, states what conclusion can be drawn from the test, and makes recommendations, where appropriate, for antibiotic therapy.


Hyperthermia in the treatment of cancer. There is now considerable evidence that heat can be used to destroy tumours. The metabolism of many types of cancer cell is selectively damaged at temperatures of 42-43 degrees C, and deficient tumour blood-flow at raised temperature represents a further exploitable Achilles heel. A striking feature of tumour heating is that metastases may regress with cure of the host; this has occurred with recurrent melanoma and sarcomas of the limbs. Heat acts synergistically with X-rays and some cytotoxic drugs to increase the therapeutic ratio for local tumour control. Guidelines for tumour heating are now being formulated against a strong experimental background in animal systems. The association of a wide variety of disciplines from oncology to electronics has already resulted in techniques for selectively treating human tumours at 50 degrees C and in internal heat applicators for insertion via natural passages. It is predicted that heat will achieve a place, most likely as an adjuvant, in cancer therapy. Work on animals and in vitro is of limited value in helping to define this place. The complexity of the tumour/host response to heat and the deficiencies in our knowledge of the biophysics of heating militate against early routine application of hyperthermia in the clinic.


Is "idiopathic" edema idiopathic?

Is "idiopathic" edema idiopathic? Ten women with "idiopathic" edema had sodium and water retention and a rapid gain in weight when their accustomed intake of diuretics was suddenly stopped. The magnitude of these changes was directly related to the levels of plasma-rening activity before withdrawal of diuretics. Nine patients became edematous. Within 10 days of stopping diuretics, plasma-renin activity and urinary aldosterone excretion decreased to normal or below and within 20 days weight-gain and edema had subsided in seven patients. But the greatest gains in weight, in three patients, were sustained beyond 20 days. Nevertheless, a year later, two of these three patients were free of edema without the use of diuretics. Intermittent edema of unknown cause in most, if not all, otherwise healthy women seems to result from their use of diuretics, abetted in some patients by self-imposed flucuation of sodium and carbohydrate intake, and does not appear to be idiopathic.


Alternate-day versus intermittent prednisone in frequently relapsing nephrotic syndrome. A report of "Arbetsgemeinschaft für Pädiatrische Nephrologie". 23 children with frequently relapsing minimal-change nephrotic syndrome were treated with alternate-day prednisone (35 mg/m2/48 h) and 25 other patients were treated with intermittent prednisone (40 mg/m2 on three consecutive days out of seven) for six months. This was followed by six months without any maintenance steroid treatment except when relapse required a short period of prednisone therapy until remission. The number of relapsers was significantly lower on alternate-day than on intermittent treatment. In the alternate-day group, the number of relapsers and the rate of relapse was significantly less before treatment withdrawal; in the intermittent group, only the number of relapsers was reduced. An alternate-day regiment is therefore preferable to the intermittent regimen in the interrupted steroid treatment of children with nephrotic syndrome.


Clinical effects of vitamin C in elderly inpatients with low blood-vitamin-C levels. The effect of oral vitamin C has been examined in elderly long-stay inpatients known to have low levels of vitamin C in their plasma and leucocytes. 1 g of vitamin C given daily for 28 days was shown to be associated with slight, but significant, clinical improvement and weight-gain when compared with placebo therapy.


Fracturing dialysis osteodystrophy and dialysis encephalopathy. An epidemiological survey. A survey of 1293 patients in eighteen dialysis centres in Great Britain showed a highly significant rank correlation of the incidence of both fracturing dialysis osteodystrophy (osteomalacic dialysis osteodystrophy) and dialysis encephalopathy with the aluminium content of water used to prepare dialysate.


Chlorpromazine reduces fluid-loss in cholera. Because chlorpromazine inhibited cholera-toxin-stimulated intestinal adenylate cyclase and fluid secretion in laboratory animals its ability to reduce fluid-loss in human cholera was investigated. Eleven cholera patients with severe purging (360--1340 ml/h) were studied. Eight were given chlorpromazine intramuscularly (1 mg/kg of 4 mg/kg), and three were given a dose of 1 mg/kg by mouth. In the 32 hours after treatment there was an overall reduction in stool output of 66 +/- 5% in the chlorpromazine-treated patients. This decrease was significantly larger than the 26 +/- 9% reduction in stool output seen in patients not receiving the drug, who were observed at the same time in the course of their illness. The decrease in nausea and the mild sedation produced by chlorpromazine added to the patients' comfort. No hypotension was seen in these well-hydrated patients.


Polyamines: an unrecognised cardiovascular risk factor in chronic dialysis? The significance of raised polyamine (P.A.) levels in chronic-dialysis patients is unknown. Since these biologically active substances have hormone-like properties and promote cell-growth in plant and animal tissues, it is possible that they stimulate proliferation of arterial smooth-muscle cells (S.M.C.)--a central process in atherogenesis--and thereby contribute to the rapidly accelerated cardiovascular disease observed during dialysis. Such a role for P.A. is supported by tissue-culture studies, which show not only that P.A.-rich serum from dialysis patients stimulates S.M.C. growth, but also that this mitogenic effect is lost when P.A. are selectively removed from uraemic serum and restored by their addition. Although these observations provide new insights into possible mechanisms of atherogenesis, they are not surprising in view of the many known biological actions of P.A.


Heatstroke in well-wrapped infants.

Heatstroke in well-wrapped infants. In a 3-year period in Newcastle upon Tyne a sudden illness, of which the main features were fever, shock, convulsions, hepatic disturbance, and a bleeding tendency, affected 5 infants, 4 of whom died. No aetiological agent could be demonstrated, and in the absence of a satisfactory alternative diagnosis it is suggested that a principal component of the illness was heatstroke, brought about by excessive wrapping or warming during a mild infection.


Viruses in drinking-water. Reconsideration of evidence for postulated health hazard and proposals for virological standards of purity. Stringent virological standards for drinking-water have been proposed by the World Health Organisation and by others, but there is no evidence of the spread of virus infection by drinking-water that has been adequately treated to conventional bacteriological standards. There is evidence for waterborne transmission of hepatitis and viral gastroenteritis but the case for the introduction of virological standards is critically examined. It is concluded that there is no evidence that drinking-water in the U.K. contributes to the spread of virus infection, and that the introduction of virological standards for drinking-water could not at present be justified. Moreover, in the absence of any information relating the degree of viral contamination to disease, there is no logical basis on which to set the level of a practical virological standard.


[Surgical palliative procedures in patients with carcinoma of the biliary tract (author's transl)]. A report is given of 72 patients suffering from carcinoma of the extrahepatic biliary ducts. Carcinoma of the gallbladder usually grow fast invading the surrounding tissue. Thus cholecystectomy can be performed only as a pallouative procedure in most cases, and partial resection of the liver does not yield better results in general. Carcinoma of the ductus hepaticus usually grows slowly and metastases are formed lately in the course; thus patients usually die due to occlusion of the ducts and jaundice rather than due to the malignancy as such. In these cases good drainage of the bile is essential, in an early stage this can be achieved by placing a tube across the tumor, in later stages an intrahepatic cholangiojejunostomy is to be performed. The technique of this procedure and results obtained in 10 cases are reported.


The role of cytoskeleton in neuron activity. The extensive cytoskeleton present in brain tissue is composed of microfilaments, neurofilaments, and neurotubules. A clear understanding of each of these structures is required to accurately define their participation in neuronal functions. Until more is known, therefore, we are restricted to speculate on their importance to the general activity of the cell. The presence of microfilamentous proteins in nerve endings -- the sites where nerve transmission is chemically sustained -- strongly suggests their participation in the release of putative neurotransmitters, a hypothesis that may be substantiated in the near future. It follows that alteration in assembly, disassembly, or interaction among the various cytoskeletal components may permit some insight into the causes and origins of a variety of neurological alterations affecting humankind.


Immunochemistry of Yersinia enterocolitica O3 grown at different temperatures. Comparative agglutinations of homogeneous stable suspensions prepared with Yersinia enterocolitica growth at 37 degrees C and at 25 degrees C were performed with anti-sera prepared in rabbits with the bacteria grown at both these temperatures. Sera prepared with live Y. enterocolitica grown at 37 degrees C agglutinated both suspensions at a much lower titre than the sera prepared with formaldehyde-treated bacteria is grown at 25 degrees C. All the sera in which strongly precipitating antibodies were induced reacted, in agar-gel, against native and heated proteins. The small amounts of antipolysaccharides induced in all the sera reacted only in the ring test against the bacterial polysaccharides. The absorption of the sera prepared with live Y. enterocolitica grown at 37 degrees C, with antigens synthesized at 25 degrees C did not remove all the homologous antibodies; apparently, some determinants are specific for the bacteria grown at 37 degrees C. Morphological changes of the small rods to elongated bacilli and filamentous forms were observed in most cultures of the Y. enterocolitica grown at 37 degrees C; these changes coincided with a low yield of proteins and point to an inhibitory effect of the 37 degrees C temperature.


Quantitative aspects of phenyl substituted alcohol and ether bacteriostatic interaction with Escherichia coli B/5. It is well established that compounds of the class phenylalkane alcohols and ethers exert their antimicrobial action on the bacterial envelope--probably on the membrane. However, the overall stoichiometry, the number of molecules bound vs those merely added per cell, and the kinds of equilibria involved (site binding vs equipartitioning) are not clear. This work examines antimicrobial action on E. coli B/5 with eight such compounds. Directly determined binding data, plate counting viabilities, radiorespirometry, and microcalorimetry of glucose utilization were evaluated. The compounds mostly bind by simply equipartitioning, up to some threshold level, short of kill. That level depends sharply on the number of alkane carbons in the phenyl alkane derivative, but not on the precise structure. Past the threshold, bacteriostatic action is sudden and complete, probably reflecting cooperative behaviour in the cell envelope. The amount of bound compound at the threshold level is only about 0.5 to 3% of the weight of the bacterial envelope hydrocarbon, when bacteriostasis occurs. There is an unexpectedly small dependence on cell concentration. The principal governors on where the monooxygen phenylalkanes kill cells seems to be merely their concentration or chemical potential, the number of aliphatic carbons, and the binding mechanism. Because of the cell concentration independence, the cells act as if they constituted a second phase, relative to the solution. Results from the microcalorimetric method for assay of bacteriostasis correlate well with those from plate counting or viability assays.


An audiovisual teaching model of the muscle spindle. Students in biology and medicine often have difficulty in visualizing the structure, function and disease of complex integrated body systems. One example in neurophysiology is the muscle spindle and Golgi tendon organ. A model is described which demonstrates the properties of these two muscle receptors. The model combines mechanical elements, which can change their length to represent muscle contraction, with an electronic representation of the passage of action potentials along 'nerves', indicated by light-emitting diodes and loudspeakers. The model has been in use for some years as a supplement to conventional teaching methods. In a recent questionnaire about the model, a group of medical students responded favourably. We suggest that models such as this are valuable teaching aids.


Orthopaedic undergraduate education.

Orthopaedic undergraduate education. Musculoskeletal disease in the community is common, and much of it responds to early diagnosis and preventive care. At the same time, modern orthopaedics, like so many specialist subjects, has increased significantly in depth and detail pari passu with its advances. It therefore becomes all the more important in desiging undergraduate teaching programmes in these specialist subjects to provide a comprehensive basic training programme that is flexible enough to move with the specialty. The orthopaedic undergraduate education programme in Oxford meets these requirements, embraces all aspects of the subject, and enables the medical student to examine the musculoskeletal system with confidence to interpret his findings, without making him an embryo specialist.


[Diffusion of cefamandole into the prostatic tissue (author's transl)]. From 21 patients with prostatic adenoma with an average age of 69 years, serum and prostatic tissue concentrations after a single i.v. dose of 2 grams of cefamandole were estimated. The mean serum concentrations 30 minutes after the infusion was completed, were measured with 104.8 and after 60 minutes with 51 microgram/ml. The corresponding concentrations in the prostatic adenoma tissue were after 30 minutes 32.87 and after 60 minutes 17.1 microgram/g. These data are compared with earlier findings with other caphalosporine antibiotics (cephradine, cephapirine, cephacetrile, cephalothin) in the same tissue materials at the same time points. The estimated concentrations of cefamandole in serum and prostatic tissue are suited for the treatment of infections caused by cefamandole sensitive microorganisms.


[Local therapy of burns in childhood by tanning with povidone-iodine (author's transl)]. Since the end of 1974 we have used Betaisodona instead of Mercurochrome for Grob's three stage tanning because the harmful effects of the mercury contained in the Mercurochrome could not be excluded with certainty. The results were compared in 80 patients in each case. The two groups were comparable with regard to age, degree and extent of the burns. We obtained an equally firm and rapidly drying scab using Betaisodone as with Mercurochrome. Complete loosening of the scab took 16 days with Betaisodona and 14 days with Mercurochrome. Wound infection was no more frequent than with Mercurochrome disinfection.