Staphylococcus aureus bacteremia: relationship between formation of antibodies to teichoic acid and development of metastatic abscesses.

Of 50 patients with bacteremia due to Staphylococcus aureus but without clinical evidence of endocarditis, 24 developed antibodies to the cell wall teichoic acid of S. aureus that were demonstrable by counterimmunoelectrophoresis. However, only 16 of the 24 patients developed titers of antibodies high enough for detection by passive gel diffusion. Eleven of the 16 patients developed evidence of complications due to metastatic infection. In contrast, of the 34 patients who were antibody-negative by gel diffusion, only one patient developed evidence of metastatic seeding. Thus, the development of antibodies to teichoic acid at a level detectable by the gel diffusion technique is regularly associated with complicated infections due to S. aureus that require more prolonged therapy, whereas bacteremic patients not developing such an antibody response rarely develop complications and may be treated with a two-week course of therapy.


Effect of cation content of agar on the activity of gentamicin, tobramycin, and amikacin against Pseudomonas aeruginosa.

Fifty-five strains of Pseudomonas aeruginosa were tested against arithmetic increments in concentrations of gentamicin, tobramycin, and amikacin in 14 different lots of Mueller-Hinton agar. The divalent cation content of each lot was determined by atomic absorption spectrometry. The relation between mean minimal inhibitory concentration (MIC) for strains within each lot and cation content was studied by stepwise regression. Among the cations, the content of Zn++ most highly correlated with the MIC of each aminoglycoside; however, Zn++ accounted for only 23%, 60%, and 47% of the variability in the mean MIC of gentamicin, tobramycin, and amikacin, respectively, against all strains. In two-cation models Zn++ with Ca++ or Cu++ was most highly correlated with the mean MICs of the three aminoglycosides against all strains. No divalent cation, either singly or in combination with one or two other cations, gave a good prediction of the MICs of the aminoglycosides in agar. Furthermore, there was variability in the cations that most highly correlated with the MICs for some strains. These observations support the concept that ionic strength, cations, and a variety of other as yet poorly defined components of media influence the activity of aminoglycosides against P. aeruginosa.


Carriage of Neisseria meningitidis and Neisseria lactamica in infants and children.

Asymptomatic carriage of Neisseria meningitidis and Neisseria lactamica was studied in a total of 2,969 healthy infants and children in Danbury, Conn., between October 1971 and June 1975. The prevalence of N. meningitidis averaged 0.71% during the first four years of life and increased to 5.4% by 14--17 years. Rates of carriage of N. lactamica increased from 3.8% in three-month-old infants to a peak of 21.0% at 18 months and then declined to 1.8% by 14--17 years of age. Of the children who acquired N. lactamica, 66% developed fourfold or greater rises in titers of IgG antibody to groups A, B, and/or C meningococci as determined by immunofluorescence compared with only 5% of control children. Of new carriers of N. lactamica, 40% developed increased titers of bactericidal antibody to groups A, B, and/or C meningococci as compared with 7% of noncarriers. Carriage of N. lactamica may assist in the development of natural immunity to N. meningitidis by induction of cross-reactive antibodies.


Association of infection due to Candida albicans with intravenous hyperalimentation.

Systemic candidiasis is frequently unrecognized before death of the patient because of lack of specific clinical signs, insensitive laboratory tests, and difficulties in culturing Candida albicans from the blood. Recent attention has been focused on the use of serologic testing and ocular signs to increase the rate of diagnosis of candidiasis. Because of the association between hyperalimentation fluids and disseminated candidiasis, a preliminary prospective study was carried out to determine more accurately the incidence in patients receiving hyperalimentation fluids of inapparent candida infection, candida endophthalmitis, or positive candida precipitins. Five of 23 patients developed small, white eye lesions consistent with candida endophthalmitis. Three of the five patients with eye lesions had blood cultures positive for C. albicans, and no patients without eye lesions had positive blood cultures. Candida precipitins were positive in three of the five patients with eye lesions. The results of this study suggest that unrecognized systemic candida infection may be more frequent in patients receiving hyperalimentation than previously suspected.


Immunogenicity of serogroup A and C Neisseria meningitidis polysaccharide vaccines administered together in humans.

Serogroup A and C Neisseria meningitidis polysaccharide vaccines were administered to U.S. Army recruit volunteers, either two weeks apart or at the same time into two different sites on the same arm, to determine what effect, if any, the combined administration would have on the immunogenicity of each individual component. The vaccines were found to be as immunogenic when administered together as when given separately; in fact, the data suggest a possible enhancement of the response, as measured by the radioactive antigen binding test, to both components when the two vaccines are given together.


Effects of phenobarbital and 3-methylcholanthrene pretreatment on size, sedimentation velocity, and mixed function oxygenase activity of rat hepatocytes.

SVA was used to separate liver cells from rats pretreated for 3 days with PB (40 mg/kg intraperitoneally, twice daily) or 3-MC (50 MG/KG AS A SINGLE INJECTIOn). Twelve fractions of cells were collected with s's ranging from 97 mm/hr (fraction1) to 25 mm/hr (fraction 12). Cells in each fraction were sized and counted electronically. PB caused the average volume of the largest cells recovered (fraction 1) to increase to 16, 725 micrometer3 from 10,500 micrometer3 previously reported in untreated animals. The number of cells recovered in the fast-sedimenting fractions (1 to 6) also increased, but there was only a small rise in the average model volume of hepatocytes determined prior to SVA. In cell suspensions analyzed after PB treatment no evidence was found for a discontinuity in the distribution of density-volume characteristics as previously described in hepatocytes from untreated rats. As expected, prior to sedimentation analysis, hepatocyte suspensions from rats treated with PB contained increased cytochrome P-450. The average ratio (n = 4) of P-450 in separated to unseparated cells ranged from 2.75 (fractions 1 + 2) to 0.38 (fractions 11 + 12), giving a 6.8-fold range in quantity of cytochrome per cell. Over this range, cell volume increased 4.2-fold, indicating a gradient in P-450 concentration similar to that previously reported to exist in cells from untreated rat liver. The gradient for AHH activity was 6.7-fold, suggesting that activity of MFO's paralleled the increase in cytochrome concentration. 3-MC pretreatment caused no significant increase in either size or number of cells in the fast-sedimenting fractions, but the discontinuity in density-volume characteristics which distinguished fast and slow sedimenting cells of untreated rats became marked. Furthermore, both the size and number of cells recovered in fractions 7 to 11 (which include the modal peal volume of unseparated hepatocytes) were increased. The gradient of P-450 (OR P1-450) was less steep in 3-MC-treated cells with pooled fractions 1 and 2 containing an average of 4.62 times as much cytochrome as fractions 11 and 12. The gradient for AHH was 4.29 times. The range of cell volume was 3.3-fold over this range. Additional experimental work was performed to determine whether P-450, AHH, or NADPH cytochrome c reductase exhibited differences in activity or concentration per unit of cell volume between cells on either side of fraction 7 where discontinuity had been noted. Each variable was expressed per unit of cell volume in fractions 5 and 9; ratios were compared but were indistinguishable from unity. It was concluded that induction of MFO activity had occurred equally in both populations of cells. Densities were calculated from s and cell volume. Noticeable loss of density followed PB treatment in cells of all sizes. 3-MC had less of an effect on density but enhanced the increment in density observed at fraction 7, which corresponds to the division between cells with distinct sedimentation characteristics...


Folate deficiency during intravenous hyperalimentation.

Two alcoholic patients were supported with hyperalimentation therapy during the management of complicated surgical problems. Folate deficiency was documented after ten and two weeks of intravenous feeding. One patient developed severe pancytopenia. Folic acid treatment resulted in hematologic recovery in both cases. Early development of folate deficiency in these patients seems to be related to multiple factors, viz., poor folate stores related to chronic alcoholism, poor dietary intake before and during the hospitalization, infection, prolonged gastric suction, and lack of folate in the intravenous hyperalimentation fluids. Rationale for the supplementation of folates in such patients is discussed.


Diurnal variation in plasma testosterone and cortisol in rhesus monkeys living in social groups.

Concentrations of cortisol and testosterone in the plasma of adult male rhesus monkeys living in social groups were determined during a 27-h period. Capture and venipuncture of experienced, conditioned animals did not lead to a fall in the concentration of testosterone in the plasma during the 90 min immediately after removal from the group. Both plasm cortisol and plasma testosterone concentrations showed a significant fall and rise in samples collected every 3 h during a 27-h period, even though there was considerable individual variation. During the autumn breeding season, animals showed higher concentrations of testosterone at both 10.00 and 22.00 h compared with those observed at the same times during the summer. Even though animals demonstrated significant diurnal changes, testosterone samples withdrawn at the same time of day (10.00 h) on consecutive days were significantly correlated with one another (r = 0.65, n = 27, P less than 0.01), suggesting the usefulness of sampling once a day to study potential environmental influences on plasma testosterone concentrations.


Effects of gonadectomy and oestradiol treatment on plasma luteinizing hormone concentrations in the marmoset monkey, Callithrix jacchus.

A heterologous double-antibody radioimmunoassay for marmoset LH is described in detail. The system uses NIAMDD rat LH-I-1 for iodination, NIAMDD rat LH-RP-1 as standard and anti-ovine rabbit LH 610V serum. The assay measures the level of marmoset LH in plasma and shows a maximum cross-reaction (B/Bo = 50%) of 0.3% with other rat, human or bovine pituitary hormones. The heterologous assay has been applied to the measurement of the level of LH in the marmoset after gonadectomy and after the subsequent implantation of oestradiol-17beta capsules. A clear increase in the concentration of LH in the plasma was observed by day 3 after gonadectomy and in most animals the level reached a plateau by day 9. The rates of increase in the concentration of LH and the maximum levels attained after gonadectomy were similar in male and female marmosets. The secretion of LH in long-term gonadectomized marmosets was episodic. In four of the marmosets studied, the frequency of the pulsatile discharges of LH was circhoral, whereas in the remaining five animals the frequency could not be determined. Subcutaneous implants containing oestradiol-17beta were seen to have a biphasic effect on the secretion of LH in all gonadectomized marmosets. After a transient increase in the concentration of LH (positive feedback) on day 1, levels fell markedly by day 4 and were undetectable 8 days after the implants were introduced (negative feedback).


The pattern of carbon dioxide excretion in the rainbow trout Salmo gairdneri.

1. Patterns of carbon dioxide excretion were investigated in rainbow trout (Salmo gairdneri). 2. The loss of erythrocytic carbonic anhydrase caused by severe anaemia does not affect acid/base regulation or the ability of fish to excrete CO2. 3. Bicarbonate excretion across the saline-perfused gills of trout is significant even though residence time for the saline in the gills is only 1--3 s. CO2 excretion across these saline-perfused gills is blocked by the carbonic anhydrase inhibitor, diamox. 4. The excretion of CO2 in fish is via the movement of plasma bicarbonate into the gill epithelium where branchial carbonic anhydrase catalyses the production of CO2. Fish can adjust pH by regulating bicarbonate movement across the gills. 5. The erythrocytic carbonic anhydrase is not necessary for CO2 excretion in the gills but is involved in facilitating Bohr and Root shifts to augment O2 delivery in the tissues.


Suppressor-cell induction in vitro. IV. Target of antigen-specific suppressor factor and its genetic relationships.

Antigen-specific suppressor factor produced by metabolically active in vitro-induced suppressor cells, upon further antigenic stimulation, act on nylon wool nonadherent, Ly-2-negative target cells within helper cell population, resulting in suppression of both the IgM and IgG antibody responses. Thus the target is an Ly-1+ T cell, possibly the helper cell. All the mouse strains tested so far have been able to produce the factor, and when tested in CBA or B10 mice, there seems to be no genetic restriction involved e.g., nonsyngeneic suppressor factors suppress as well as do the syngeneic factors. Comparison of the properties of suppressor factor with those of extracts of suppressor cells yield differences in origin, target of action and effect, indicating that these are different molecules. The heterogeneity of suppressor pathways is discussed.


T-cell-mediated cytotoxic immune responses to F9 teratocarcinoma cells: cytolytic effector T cells lyse H-2-negative F9 cells and syngeneic spermatogonia.

Murine thymus derived (T) lymphocytes primed in vivo to mouse 129 (H-2bc) derived H-2-negative F9 embryonal carcinoma cells and rechallenged in vitro with X-irradiated F9 stimulator cells differentiated into anti-F9 cell immune cytotoxic T lymphocytes (CTL). Using CBA mouse derived splenic responder T cells, F9 stimulator cells triggered a primary cytotoxic anti-F9 response. The CTL generated lysed the F9 antigen-positive target cells F9. PCC3 and PCC4, but not the F9 antigen-negative mouse 129 derived PYS tumor cells, nor LPS induced H-2bc blast cells. Mouse 129 anti-F9 cell antisera but not H-2k anti-H-2bc antisera blocked the lytic interaction with F9 target cells. Similarily unlabeled F9 cells but not H-2bc blast cells inhibited the anti-F9 cell cytotoxicity H-2k anti-F9 cell immune CTL were found to be cytotoxic for syngeneic spermatogonia, known to express the F9 antigen. The results suggest not only that CTL can recognize and lyse H-2-negative target cells, but also that CTL precursors can be sensitized against H-2-negative stimulator cells. From the data available it may be inferred that anti-F9 Cell immune CTL recognize the F9 antigen, known to be linked with the T/t locus. Since anti-F9 cell immune CTL lyse syngeneic spermatogonia, the system may be useful to analyze in vitro the induction and effector phase of a T-cell-mediated cytotoxic autoimmune orchitis.


Genetic control of the immune response to staphylococcal nuclease. VII. Role of non-H2-linked genes in the control of the anti-nuclease antibody response.

The role of non-H-2-linked genes in the control of the antibody response to staphylococcal nuclease has been investigated. 3 wk after immunization with nuclease in complete Freund's adjuvant, strain A/J (H-2 a) mice produced significantly higher titers of antibody than strain B10.A (H-2(a)) mice, whereas mice of strains A.BY (H-2(b)) and B10 (H-2(b)) produced barely detectable titers. With hyperimmunization, A/J and A.BY mice reached the same peak levels for antibody titers, both severalfold higher than those reached by B10.A and B10 mice. Analysis of the specificity of antibodies by assessment of binding to two fragments of nuclease showed similarities between strains of the same H-2 haplotype. These results suggest that although H-2-1inked genes determined initial responsiveness at 3 wk and the relative proportions of antibodies directed toward different antigenic determinants on the nuclease molecule, non-H-2-linked genes determined the overall magnitude of the hyperimmuneresponse. Measurement of the affinity of the antibodies to the nuclease fragment (1-126) showed that strains B10 and B10.A produced antibodies with 7- to 10-fold higher affinity than comparable antibodies from strains A.BY and A/J. In a backcross of (B10.A x A/J) x B10.A, the level of antibody segregated independently of the Ig-1(e) C(H) allotype and the A/J anti-nuclease idiotypes. Thus, a gene(s) linked to neither H-2 nor heavy chain structural genes appears to control the aggregate response to antigenic determinants on the nuclease molecule independent of subspecificities of these antibodies or their idiotype.


Mechanisms of genetic resistance to Friend virus leukemia in mice. IV. Identification of a gene (Fv-3) regulating immunosuppression in vitro, and its distinction from Fv-2 and genes regulating marrow allograft reactivity.

Friend leukemia viru (FV) suppresses the proliferative response of normal lymphocytes to mitogens. The in vitro suppressive effect of FV on lymphocyte mitogenesis is mediated by T-suppressor cells and is under host genetic control. Lymphocytes from strains of mice of the C57BL background (e.g., C57BL/6) are resistant while cells from other strains (e.g., 129 and DBA/2) are susceptible. Genetic analyses utilizing resistant and susceptible parental strains, their F1, intercross and backcross progeny indicated that susceptibility to in vitro suppression is regulated by a single autosomal gene, dominant for susceptibility to suppression. This gene, which is not linked to the H-2 complex, segregated independently of the Fv-2 gene which controls resistance to spleen focus formation in vivo. The gene is also unlinked to the Ir-like genes which regulate the ability of H-2d mice to reject H-2b bone marrow grafts. The gene is therefore designated as Fv-3. Fv-3 may mediate its effect by regulating the numbers and/or functions of T-suppressor cells.


Two distinct types of helper T cells involved in the secondary antibody response: independent and synergistic effects of Ia- and Ia+ helper T cells.

We have described here two distinct types of carrier-specific helper T cells which act independently and synergistically to augment the B-cell response to a hapten. They are separable by passage through a nylon wool column. The first type of helper T cell, which we designate as Th1, is nylon nonadherent, and can help the response of hapten-primed B cells only if the haptenic and carrier determinants are present on a single molecule (cognate interaction). The second type of helper T cell, Th2, adheres to the nylon wool column, and can help the B-cell response to a hapten coupled to a heterologous carrier upon stimulation with unconjugated relevant carrier (polyclonal interaction). The addition of a small number of Th2 to the mixture of Th1 and B cells significantly augmented the net response to the hapten carrier conjugate. Both Th1 and Th2 cells belong to the Lyt-1+,2-,3- subclass. Th1 has no detectable Ia antigen, whereas Th2 is killed by certain anti-Ia antisera and complement. The Ia antigen detected on Th2 was found to be controlled by a locus in the I-J subregion. The results clearly established the fact that there are two distinct pathways in the T- and B-cell collaboration, which involves two different subsets of carrier-specific helper T cells.


Expression of a single major histocompatibility complex locus controls the immune response to poly-L-(tyrosine, glutamic acid)-poly-DL-alanine-poly-L-lysine.

Genetic control of the immune response linked to the major histocompatibility (H-2) complex in the mouse has been described for synthetic polypeptide antigens and for low doses of native proteins. The phenomenon is well documented(1,2). Extensive screening of intra-H-2 crossover-derived recombinant strains has localized H-2-linked immune response (Ir) genes to the I-immune response region of the H-2 complex (3). For most antigens, Ir genes are autosomal, dominant, and they segregate as single loci. It is not known whether these crossover-defined loci respresent single genes with multiple alleles or clusters of tightly linked genes (4). In 1972, Stimpfling and Durham (5) postulated that two interacting loci within the H-2 complex were required for the response to the alloantigen, H-2.2 (6), and, in 1975, Dorf et. al. (7) observed a responder phenotype in a recombinant derived from two strains which were nonresponders to the synthetic linear terpolymer, L-glutamic acid, L-lysine, L-phenylaline (GLPhe). Analysis of additional recombinants and complementation tests with F(1) hybrids clearly demonstrated that genes in two intra-I-region loci controlled the immune response to GLPhe. Subsequently, requirement for genes mapping in two intra-I-region loci were reported for porcine LDH(B)(8), the alloantigen Thy-1.1 (9), and for the synthetic terpolymers L-glutamic acid, L-lysine, L-tyrosine and L-glutamic acid, L-lysine, L- leucine (6,10). Demonstration that responses to both synthetic polypeptide and native protein antigens can be controlled by genes in two distinct I-region loci prompted speculation that the phenotypic expression of two I-region genes is a general phenomenon which may provide the key for understanding the mechanism of Ir gene function and cellular collaboration in the immune response. Benacerraf and Dorf (10) have shown that Ir gene complementation is often more effective in the cis than in the trans configuration. This concept is further supported by the data reported for GLPhe (10-12) which indicate that both of the complementing genes must be expressed in each of the cell types participating in the interaction. Failure to detect complementation for the majority of antigens under H-2-linked Ir-gene control might be attributed to the limited number of available intra-I- region recombinant strains.


Tubulin and microtubule-like structures in mammalian acrosomes.

Immunofluorescence and electron microscopy were used to demonstrate the presence of tubulin and microtubule-like structures in rabbit and rhesus monkey sperm acrosomes. The distribution of tubulin within the acrosome appeared similar to the distribution of proteolytic activity, suggesting an association of proteinase with these structures. Electron microscopy of rhesus monkey sperm incubated in vitro demonstrated a progressive condensation of the acrosomal matrix into microtubule-like structure. A system of this type could explain the linear patterns of silver-proteinate staining in the pentration tunnel through the zona pellucida.


An autoradiographic evaluation of the regeneration of corneal epithelium in Bufo marinus.

Epithelial regeneration following scraping of a central portion of corneal epithelium of the toad, Bufo marinus, was studied. Wound closure occurred by migration of a single layer of epithelial cells from adjacent noninjured areas. Autoradiography indicated that following wound closure at two days after scraping, DNA synthesis began in these epithelial cells covering the former scraped area, and was even more pronounced three days after scraping. At four days the former denuded area was covered by an epithelium two to four cells thick and by the fifth day regeneration was complete. These studies also indicated that mitotic time in this organism is rapid.


Rabbit acrosin: immunological dissimilarity to rabbit trypsin (1).

Antibodies obtained from guinea pigs injected with rabbit pancreatic trypsin together with antibodies raised in rabbits against bovine acrosin or bovine pancreatic trypsin were reacted against various mammalian trypsins and acrosins in double diffusion tests. The results of immunodiffusion analyses reveal antigenic dissimilarity between rabbit acrosin and rabbit trypsin.


Role of vascular proliferation on angiographic appearance and encapsulation of experimental traumatic and metastatic brain abscesses.

Experimental traumatic abscesses were produced in rhesus monkeys by intracerebral injection of nutrient agar contaminated with Staphylococcus epidermidis, and metastatic abscesses were induced by intracarotid embolization of silicone cylinders contaminated with Staphylococcus epidermidis. All monkeys underwent preoperative and serial postoperative carotid angiography. Traumatic abscesses produced early capsular blushes and progressive anterior cerebral artery displacements. Metastatic abscesses induced transient midline shifts but no capsular stains. Postmortem studies on the monkeys showed that mean capsular thickness and segmental wall vascularity of the traumatic and metastatic abscesses were significantly different (p less than 0.001), despite equal abscess ages and similar abscess volumes. In comparison to traumatic abscesses, metastatic abscesses demonstrated reduced inflammatory cell infiltration and retarded collagen formation around proliferating capsular vessels. Brain surrounding the metastatic abscesses demonstrated ischemic changes. The results suggest that 1) capsular blushes during cerebral angiography are secondary to vascular proliferation within the capsule and not to compression of surrounding brain, 2) vascular staining reflects capsular thickness, 3) capsular vascularity contributes to collagen formation, 4) encapsulation is dependent upon the integrity of surrounding brain, and 5) adjacent cerebral ischemia may impede inflammatory responses involved in capsule formation.


A new hemogregarine from marine fishes.

Haemogregarina uncinata sp. n. is described from the blood of 2 marine eelpouts, Lycodes lavalaei and Lycodes vahlii (Perciformes: Zoarcidae). Erythrocytic schizogony occurred in peripheral and cardiac blood, but mature schizonts were restricted to the latter site. Mature and rupturing schizonts contained 10 to 30 merozoites, which were short and thick in small schizonts while slender and long in larger schizonts. Gametocytes developed in mature erythrocytes and displayed morphologic and morphometric characters that distinguished them from other species described. Syzygy and gamete formation occurred in the gut of a leech, Johanssonia sp. Each microgametocyte produced up to 4 apparently nonflagellated gametes. Oocysts developed intracellularly in the epithelial wall of the intestine and at maturity produced under 100 sporozoites from (apparently) several germinal centers. Sporozoites subsequently migrated to the probosces of the leeches. The failure to transmit the parasite to a sculpin (Myoxocephalus octodecemspinosus) and 3 Atlantic cod (Gadus morhua) via regurgitation by the leeches might be indicative of host specificity.


Diencephalic efflux of calcium ions in the monkey during exercise, thermal stress and feeding.

1. The diencephalon of the unanaesthetized macaque monkey was radio-labelled with calcium by a microinjection of 6-8 muC (45)Ca(2+) into the third cerebral ventricle through a permanently implanted cannula. Successive 5 min push-pull perfusions of the mid-line hypothalamic region with an artificial C.S.F. were carried out at a rate of 28 mul./min every 20 min. A washout curve of declining (45)Ca(2+) radioactivity was thus generated.2. When the monkey exercised strenuously on a special ;rowing machine' to obtain highly palatable banana pellets, its body temperature rose sharply. As the monkey exercised, during a sequence of push-pull perfusions, the concurrent efflux of (45)Ca(2+) ions increased markedly in the corresponding samples of diencephalic perfusate. This enhanced activity of calcium ions continued throughout a 30 min work period and persisted as long as the monkey's temperature was elevated in the interval immediately following exercise.3. Exposure of the monkey's trunk, between neck and thigh to cold air of 5 degrees C likewise augmented the amount of (45)Ca(2+) ions in the diencephalic push-pull perfusates; however, a similar exposure to air warmed to 35 degrees C failed to alter the pattern of (45)Ca(2+) efflux from the animal's diencephalon. If a fasted monkey consumed only the banana pellets but was not exercised, the level of (45)Ca(2+) in the perfusate also increased transiently, just at the onset of feeding.4. We conclude that a local change in calcium transport, binding or other cellular activity of the cation within the diencephalon could play an important role in the central mechanism underlying the set-point rise in a primate's temperature which accompanies vigorous exercise. Further, the results support the idea that this cation functions in the diencephalic control of metabolic heat production as well as in the overall processes of energy metabolism, particularly in relation to feeding.


Studies on the mechanism of renin release from isolated superfused rat glomeruli: effects of calcium, calcium ionophore and lanthanum.

1. The effects of external medium calcium concentration, the ionophore A(23187) and lanthanum on the rate of renin release in vitro were studied with particular emphasis on results obtained from isolated superfused glomeruli of rat kidneys.2. The response to reduction in superfusate calcium concentration from 2 mM was a graded and reversible increase in the rate of renin release. An increase in release was detectable at 0.2 mM calcium; a threefold increase was found 36 min after a change from 2 mM calcium to calcium-free superfusate. A similar relative increase in release resulted from reductions from 0.1 mM to zero calcium, but the absolute amounts of renin released were greater in this latter series. Renin release from kidney cortical slices similarly increased in response to calcium-free incubation medium.3. The effects of A(23187) on renin release were modest. Changing from 2 mM calcium during control periods to calcium-free Ringer with A(23187) added caused an attenuated and more delayed increase in release than the change to calcium-free Ringer without ionophore. This difference in response was abolished when glomeruli were superfused with 0.1 mM calcium during the preceding 1 hr control period. There was no significant difference in renin release from glomeruli exposed to calcium-free EGTA-Ringer with and without A(23187) in the 2 mM calcium series; in the 0.1 mM calcium series the increase in release following a shift to calcium-free EGTA-containing superfusate with A(23187) added was significantly greater than in the absence of the ionophore.4. Addition of lanthanum (1 or 0.05 mM) to calcium-containing as well as calcium-free superfusate resulted in a significant depression of renin release. Subsequent removal of the lanthanum did not restore the rate of release unless EGTA was added; in the latter case a massive increase in renin release occurred resulting in a marked depletion of the remaining renin content of the glomeruli.5. It is concluded that calcium influences renin release by a direct action on the juxtaglomerular cells. The data support the previous suggestion that basal renin release is a function of active, calcium-dependent cell volume regulation - swelling causing an increase in the release; and further suggest that membrane-bound calcium has a direct effect on the cell membrane permeability to renin.6. The results exclude that calcium-stimulated exocytosis is responsible for basal renin release from the juxtaglomerular cells adhering to isolated glomeruli.


Congenital ocular anomalies in Pondicherry.

Congenital anomalies of the eye and ocular adnexa occurring in Pondicherry have been described. Anophthalmos, microphthalmos, limbal dermoids, nervus of Ota, anterior lenticonus, buphthalmos, and congenital cataract are very common. Onset of cataract in young individuals was caused by abnormal aminoaciduria. Hereditary factors played a part in 59 percent of the cases who would have become blind if they were not treated. Consanguinity is a major factor in their pathogenesis. Avitaminosis A and systemic infections which are common here may be playing a significant role in their etiology.


The visual pigments of rods and cones in the rhesus monkey, Macaca mulatta.

1. New microspectrophotometric measurements have been made of the photo-pigments of individual rods and cones from the retina of the rhesus monkey (Macaca mulatta). The measuring beam was passed transversely through isolated outer segments. 2. The transverse absorbance for rods ranged from 0.02 to 0.04 and that for cones from 0.01 to 0.03. 3. The mean absorbance spectrum for rods (n = 25) had a peak of 502 +/- 2.7 nm. A digitonin extract from the same group of eyes gave a lambda-max. of 499 +/- 1 nm. 4. Of a sample of 82 cones, 40 were 'red' (P565 nm) and 42 were 'green' (P536 nm). The mean absorbance spectrum for the green cones is very similar to the Dartnall nomogram, but that for the red cones is narrower. 5. No bleachable, blue-sensitive outer segments were recorded, although structures were found that absorbed at short wave-lengths and were neither photosensitive nor dichroic. 6. If the long wave-length and middle wave-length cone pigments of the rhesus monkey are assumed to be identical to those of man and if additional assumptions are made about the lengths of human outer segments and about prereceptoral absorption, it is possible to derive psychophysical sensitivities that closely resemble the pi5 and pi4 mechanisms of W. S. Stiles.


Calcium-dependent repolarization in Paramecium.

1. Intracellular injection, recording and current-passing methods were used to investigate the role of intracellular Ca in the modulation of electrical behaviour in the ciliate Paramecium caudatum.2. Injection of EGTA converted graded regenerative responses ascribed to Ca inward current to all-or-none action potentials. The EGTA injection also caused a discontinuity in the steady state I-V relations to outward current, but had little effect on hyperpolarizing current-voltage responses.3. The overshoot of the all-or-none spike produced by the EGTA-injected cell followed an approximate 29 mV increase for a tenfold increase in external Ca concentration and was independent of changes in external K and Na concentrations.4. The EGTA-induced all-or-none action potential tended to produce plateaus that could last up to 20 sec. During the plateau the membrane slowly repolarized to a critical potential, upon which repolarization occurred precipitously.5. Injection of 10(-6)M-free Ca(2+) as a Ca-EGTA buffer hyperpolarized the membrane and decreased the potential shifts to inward current pulses. These responses are consistent with an increase in K conductance.6. During EGTA plateaus reversed beating of the cilia indicated a rise in intracellular Ca, and thus an inability of the EGTA to complex the Ca as rapidly as it entered the cilia. Reversal of the motile apparatus thus appears to be activated at lower concentrations of intracellular Ca than are required to activate the inferred Ca-dependent K system.7. In uninjected cells removal of the cilia, which results in a loss of the voltage-activated Ca channels (Dunlap, 1977), or addition of extracellular Ba both tended to linearize the steady state I-V relations.8. Injections of Cs and TEA tended to linearize the steady state I-V relations, but did not result in either a conversion to an all-or-none spike or a discontinuity in the depolarizing steady-state I-V relations.9. It is concluded that in Paramecium a Ca-activated K conductance short-circuits the inward current of the regenerative Ca response, preventing all-or-none behaviour. The occurrence of plateau spikes following EGTA injection indicates that the Ca conductance inactivates very slowly in face of a maintained depolarization. Such slow Ca-inactivation is consistent with the slow relaxation of Ca-dependent ciliary reversal that occurs during maintained depolarization.10. The possibility is discussed that injection of EGTA may also enhance the Ca conductance.


Treatment of fetal distress during diabetic keto-acidosis.

A case of diabetic acidosis during pregnancy is presented in which the fetal heart rate tracing demonstrated late decelerations. Sodium bicarbonate, intravenous fluids and insulin treatment resulted in correction of both the maternal acidosis and the abnormal fetal heart rate tracings. The rationale for bicarbonate therapy for treatment of the presumed fetal distress is discussed.


Sporadic (nonepidemic) puerperal mastitis.

Sporadic puerperal mastitis is an acute cellulitis, characterized by fever and segmental erythema in the breast. Staphylococcus aureus can be cultured in approximately one-half of the cases. With early antibiotic therapy, the infection can be cleared and abscess formation prevented. Breast engorgement may also contribute to abscess formation, and so nursing should not be discontinued. No ill effects are observed in infants who continue to nurse. Twenty women with acute puerperal mastitis had breast milk cultures, and Staphylococcus aureus was recovered in seven cases. All patients were treated with antibiotics and continued nursing. No abscesses developed, and no ill effects were observed in any infants.


Reduced Fc-receptor bearing cells in peripheral bloods of patients with systemic lupus erythematosus and in rheumatoid synovial fluids.

Previous reports described that human red cells sensitized with one of Rh antisera (Ripley) make rosette formations (Fc-rosette with some lymphocytes. These Fc-rosettes were well inhibited by aggregated human IgG as well as hypocomplementemic systemic lupus erythematosus (SLE) sera and rheumatoid synovial fluids. In the present study, Fc-receptor bearing lymphocytes were considerably reduced in peripheral bloods of SLE (16.0 +/- 7.6%) and rheumatoid synovial fluids (15.6 +/- 5.3%). On the other hand, EAC-rosette formation rates of peripheral bloods of SLE (32.0 +/- 13.2%) and rheumatoid synovial fluids (30.3 +/- 11.2%) did not significantly differ from normal peripheral bloods (28.3 +/- 2.9%). E-rosette forming lymphocytes were reduced in peripheral bloods of SLE (48.7 +/- 15.7%) and in rheumatoid synovial fluids (49.0 +/- 14.6%) whereas 61.7 +/- 8.6% in normal peripheral bloods. Reduced Fc-rosette formation rates correlated well with the Fc-rosette inhibitory rates. In addition, eluates from the lymphocytes in rheumatoid synovial fluids also inhibited Fc-rosette formation. These results suggested that immune complexes present in peripheral bloods of SLE and rheumatoid synovial fluids are bound to the Fc-receptors on the lymphocytes, block the additional binding of the sensitized red cells, and result in the reduction of Fc-rosette formation.


Meningococcemia presenting as acute polyarthritis.

Four patientw with acute polyarthritis due to meningcoccemia are described. One had skin manifestations suggesting vasculitis, another had transient nodular lesions, but there were none of these features in the other two. Synovial fluid cultures were negative and cells counts did not suggest septic arthritis. The diagnosis was not suspected until positive blood cultures were reported in three cases and meningitis developed in the fourth. In spite of diagnostic delay due to slow growth in cultures (six to 11 days) there was prompt response to antibiotic treatment. Meningococcemia should be suspected in patients presenting with fever and polyarthritis, even in the absence of skin lesions.


Reproducible chromosome changes of polycyclic hydrocarbon-induced rat leukemia: incidence and chromosome banding pattern.

Statistical analysis of 361 cases of primary leukemia induced in outbred Long-Evans and Sprague-Dawley rats by 7,12-dimethylbenz[a]anthracene (DMBA) and 7,8,12-trimethylbenz[a]anthracene (TMBA) showed that the incidence of trisomy of chromosome No. 2 was significantly lower with TMBA (17.8%) than with DMBA (29.3%). This tendency was reproducible in both sexes. Another characteristic chromosome abnormality, long No. 2, was found in 10 cases (2.8%). Quinacrine fluorescence analysis revealed that cells with No. 2 trisomy or either of two types of long No. 2 had total and partial No. 2 trisomy, respectively. Other chromosome members of cells with long No. 2, as well as the chromosomes of cells with typical No. 2 trisomy and "normal diploid" leukemia cells, revealed no band abnormality. The phenotype of No. 2 trisomy, severe anemia of the hosts reported in DMBA-induced leukemias, was also noted in leukemias with TMBA-induced No. 2 trisomy but not in leukemias with long No. 2.


Age-related modification of 7,12-dimethylbenz[a]anthracene binding to rat mammary gland DNA.

The binding of 7,12-dimethylbenz[a]anthracene (DMBA) to mammary gland and liver DNA of female Sprague-Dawley rats either 35, 50, or 120 days of age at the time of carcinogen administration was studied. Following a single oral feeding of tritium-labeled DMBA, the level of binding to liver DNA of rats in all 3 age groups was significantly lower, at all times during a 6-week period, than that of binding to mammary DNA. The amount of DMBA bound to liver DNA was a function of the amount of carcinogen administered and not the age of the animal. In contrast, DMBA binding to mammary DNA was dependent on the age of the animal at the time of carcinogen feeding. Furthermore, in the age group with 100% tumor induction (50 days old), DMBA binding increased directly with the amount of carcinogen fed; this was not the case for the other 2 age groups. These results indicated that a significant correlation existed between the age of the rat, the amount of DMBA bound to DNA, and the incidence of mammary tumors following carcinogen feeding.


Distinct glycosylation of serum proteins in patients with cancer: brief communication.

Concanavalin A and wheat germ agglutinin, lectins that interact with serum glycoprotein in a manner similar to the antigen--antibody reaction, were used as "antibodies" in a single radial immunodiffusion technique to test a coded serum panel (from the National Cancer Institute, Bethesda, Md., and the Mayo Clinic, Rochester, Minn.) containing a) 99 serum samples from patients with different types of malignant neoplasms of the gastrointestinal tract, prostate gland, and lung, b) 50 samples from patients with benign diseases of the same organs as those affected in the cancer patients, and c) 50 samples from apparently healthy smokers. The resulting precipitation rings were not correlated to serum protein concentration, and the differences (demonstrated by Student's t-test and with a generalization of the one-sided two-sample Kolmogorov-Smirnov statistic for evaluating diagnostic tests) established that serum glycoproteins are glycosylated differently in cancer patients than in people without cancer.


Translation of RNAs synthesized in vivo and in vitro from bacteriophage SP82 DNA.

The synthesis of 69 phage-specific polypeptides during the infection of Bacillus subtilis with bacteriophage SP82 was detected by pulse-labeling, one-dimensional electrophoresis, and autoradiography. SP82 virions were found to contain approximately 22 polypeptides, most of which were synthesized late in infection; evidence was obtained for the processing of the major virion protein. RNAs extracted at different times during infection were translated by using an Escherichia coli cell-free extract. Only smaller-molecular-weight peptides were produced efficiently in vitro; in the 9,000- to 60,000-molecular-weight range, 50 to 60% of the peptides synthesized in vivo were produced by translation of RNAs extracted from infected cells. Eight of the virion peptides were produced by in vitro translation of RNAs extracted from infected cells. RNAs were synthesized under defined conditions by RNA polymerase extracted from uninfected B. subtilis and by polymerases isolated from cells 8 and 20 min after infection with SP82. Translation of these RNAs yielded characteristic and different patterns of polypeptides. Nine of the 12 polypeptides produced by translation of RNAs synthesized by the host polymerase corresponded in mobility to peptides appearing in vivo in the 0 to 3 and 3 to 6 min intervals of pulse-labeling after infection; 12 of the 25 peptides synthesized from RNAs produced by polymerase extracted 8 min after infection corresponded in mobility to peptides detected in vivo 8 min after infection, and 15 of the 22 peptides directed by RNAs made by the polymerase isolated 20 min after infection corresponded to peptides present in vivo late in infection. Five of the peptides produced in vitro from the latter RNA corresponded to virion peptides.


Incorporation of label from ribose into 5-(4',5'-dihydroxypentyl) uracil of bacteriophage SP15 DNA.

Radioactively labeled ribose was incorporated into the glucosylated deoxynucleoside monophosphate of 5-(4',5'-dihydroxypentyl)uracil of bacteriophage SP15 DNA to a greater extent than into the other pyrimidine deoxynucleoside monophosphates. Results from formic acid hydrolysis of the deoxynucleoside monophosphates to their bases suggest that label from ribose is incorporated into the dihydroxypentyl side chain of 5-(4',5'-dihydroxypentyl)uracil.


Isolation of a Bacillus subtilis 168 derivative sensitive to defective bacteriophage PBSX.

A derivative of Bacillus subtilis strain 168 sensitive to defective bacteriophages PBSX and PBSZ has been isolated. This particular strain, RUB824, carries the genetic information for defective bacteriophage PBSX.


Diagnostic evaluation of hypertension: pilot study in a hypertension clinic.

Two hundred and eighty-two (282) patients suffering from hypertension were evaluated for the detection of secondary forms of hypertension. Apart from clinical and routine laboratroy investigation in each, straight film of abdomen, intravenous pyelography (IVP), isotope renography and aortography were done in 174, 51, 109 and 2 cases respectively. Evidences of secondary hypertension was present in 22(7.8%) of which renal aetiology was probable in all but 4. Of the 10 patients with a primary kidney condition, possible renal aetiology was unsuspected in only one patient with unilateral renal hypoplasia. In 8 patients with renal involvement due to systemic disease, or in 4 with non-renal causes, the aetiological diagnosis was suggested by the clinical situation. In view of low yield of curable hypertension and high cost, IVP and renography should only be employed selectively and not as routine investigations.


Thyroid-stimulating hormone (tsh), triiodothyronine (t3) and thyroxine (t4) response to intravenous and oral stimulation with synthetic thyrotropin-releasing hormone (trh) in young healthy adults.

TSH, T3 and T4 response to stimulation with thyrotropin releasing hormone (TRH) has been investigated in 24 young healthy adults after intravenous injection and in 25 young healthy adults upon oral application of 40 mg of TRH. After intravenous injection the TSH concentration raises from a mean of 1.6 to a mean maximum of 11.7 muU/ml. A statistically significant sex difference could not be found. T3 shows a statistically significant increase which is however too small to be of diagnostic value in an individual test. After oral stimulation with 40 mg of TRH, TSH rises to a slightly higher maximum of 13.2 muU/ml after 3 h. The T3 increase from 1.5 to 2.19 ng/ml is significant and considerably higher than after intravenous stimulation. The thyroxin increase is statistically significant. The present results compare well with previously published data for intravenous stimulation. The oral route of TRH application has not yet been widely used and the present series establishes the normal response in young healthy adults. Repetitive stimulation with three times 40 mg of TRH leads to a decrease in TSH stimulation which reaches 5.8 muU/ml 3 h after the third dose. This is in contrast to a comparable increase in plasma T3.


[Bone mineral content during chronic hemodialysis long term observation by 125-i photonabsorptiometry (author's transl)].

40 out of 98 patients on chronic haemodialysis show an obviously lowered bone mineral content of the radius (mean -20.4%), 51 patients attain values in the normal range (mean -1%) and 7 subjects slightly increased values (mean +10.9%). A bone mineral loss of 2.5% could be found after long-term observations of this parameter between 6 to 30 months (mean observation period: 15 months). In general a progressive loss of the bone mineral content may be noticed with an increased duration of haemodialysis. This tendency is more distinct after the 40th year of life because of the simultaneous age-depending physiological decrease of bone mass. Abruptly occurring mineral losses of the skeleton may be due to a high incretion of parathyroid hormone and possibly require subtotal parathyroidectomy.


A serological survey of accredited breeding colonies in the United Kingdom for common rodent viruses.

This paper reports the results of a general survey, the first in the United Kingdom, carried out on accredited breeding colonies of mice, rats and guinea-pigs over a period of a year. While the results show the potential usefulness of a viral accreditation grading scheme, they also show that contamination of breeding colonies with inapparent viral infections is widespread. This situation can only be improved by the continuous monitoring of animal stocks for rodent viruses, with the aim of improving the standard of animals available for research and for pharmacological, toxicological and routine diagnostic procedures.


On the rate limiting step in downhill transport via the LacY permease of Escherichia coli.

Strains of Escherichia coli K12 were constructed for the specific purpose of evaluating the inducibility of the influx mechanism controlled by the lacY gene. These strains are heteromerodiploids characterized by a high and relatively constant level of beta-D-galactosidase which is not affected significantly by induction of the Lac operon. These properties were obtained by introducing episomal lacI+,Oc,Z+,Y-genes into the cells. In these merodiploids the rate of o-nitrophenyl-beta-D-galactopyranoside (ONPG) hydrolysis of extracted cells is 50-times that of intact cells. This difference indicates that the rate limiting step in the ONPG hydrolysis by intact cells is influx. Using a set of merodiploids with and without the LacY transport system, we were able to demonstrate a specific induction of ONPG influx. However, the increase in influx due to induction was only 3.5-fold as compared to the 40-fold increase observed when the LacY permease was measured by intracellular accumulation of [14C]TMG.


The inhibitory effect of the artificial electron donor system, phenazine methosulfate-ascorbate, on bacterial transport mechanisms.

The artificial electron donor system, phenazine methosulfate (PMS)-ascorbate, inhibited active transort of solutes in Pseudomonas aeruginosa irrespective of whether the active transport systems were shock sensitive or shock resistant. N,N,N',N'-tetramethylphenylenediamine could be substituted for PMS but a higher concentration was required. PMS-ascorbate also inhibited active transport in several other bacterial species with the exception of Escherichia coli and of a nonpigmented strain of Serratia marcescens. PMS-ascorbate previously has been shown to energize active transport in isolated membrane vesicles, even those prepared from the same bacterial species in whose intact cells active transport was inhibited. The apparent Km of glucose active transport in untreated cells of P. aeruginosa was 40 micron while the Km of glucose transport in cells incubated with PMS-ascorbate was 25 mM, and PMS-ascorbate had no effect on efflux of accumulated glucose. These results strongly suggested that facilitated diffusion resulted upon exposure of the cells to PMS- ascorbate. Thus, PMS-ascorbate appeared to have an uncoupler-like effect on cells of P. aeruginosa. The experimental data also pointed out that there are fundamental differences between the response of intact cells and membrane vesicles to exogenous electron donors.


Protein and energy sparing of glucose added in hypocaloric amounts to peripheral infusions of amino acids.

After abdominal surgery, patients were given peripheral infusions of amino acids alone for 4 days followed by amino acids plus glucose for 4 days, or the same solutions in the reverse order. Although there was a wide variation in the response of individual subjects, the typical effect of glucose under these conditions was to reduce both nitrogen excretion (average of 2.8 g N/day) and resting metabolic expenditure (average of 110 kcal/day).


[Surgical problems of diverticulosis of the small intestine (author's transl)].

Two patients are reported which were operated for complications of small bowel diverticula. One was operated for a retroperitoneal tumor caused by a perforated diverticulum, which led to an inflammatory mass of the mesentery. In another patient adhesions produced acute intestinal obstruction.


Chromosome mobilization by the R plasmid R68.45: a tool in Pseudomonas genetics.

The conjugative plasmid R68.45 mobilizes the chromosome of Pseudomonas aeruginosa strain PAO from multiple sites located in different chromosome regions. In interrupted matings on the plate, selection for any single marker tested resulted in entry times of 3-5 min. When selection was imposed  for two markers linked in R68.45-mediated conjugation, double recombinants appeared after a delay which corresponded approximately to the map distance between the two markers as measured by the sex factor FP2. Thus, R68.45 and FP2 appear to promote chromosome transfer at similar rates, but R68.45, unlike FP2, seems to give non-polarized transfer. R68.45 may be used to estimate map distances between linked markers located in those chromosome regions where other sex factors do not produce enough recombinants to permit accurate measurement of entry times. In R68.45 matings on the plate, most recombinants inherited short donor chromosome fragments (usually less than 10 min long) and lost the R plasmid during purification. Used like a "large" generalized transducing phage, R68.45 has proved valuable in construction of PAO strains with desired genotypes.


Cloning of Bacillus subtilis leucina A, B and C genes with Escherichia coli plasmids and expression of the leuC gene in E. coli.

The leucine genes of Bacillus subtilis have been cloned directly from the chromosomal DNA into Escherichia coli leuB cells by selection for the Leu+ phenotype using RSF2124 as a vector plasmid. The hybrid plasmid designated RSF2124-B.leu contained a 4.2 megadalton fragment derived from B. subtilis DNA, including the leu genes. The fragment had one site susceptible to EcoRI* and another site susceptible to BamNI endonuclease. Among the three fragments produced by EcoRI* and BamNI endonucleases, the 1.2 megadalton fragment had the ability to transform B. subtilis leuA, leuB and leuC auxotrophs to leu+. However, B. subtilis ilvB and ilvc auxotrophs were not rescued even by the whole 4.2 megadalton fragment present in the hybrid plasmid. beta-Isopropylmalate dehydrogenase (leuB gene product) activity found in E. coli cells containing the hybrid plasmid was about 60% of that in E. coli wild type cells, despite the high copy number (7.8) of the plasmid per chromosome observed.


[Recognition of bacterial infections in newborns by measuring specific antibody-titres (author's transl)].

Antibodies were measured in 172 unselected neonates against mixed polyvalent antigens derived from E. COLI, Klebsiella, Ps. aeruginosa and Proteus spp. respectively, using a modification of the indirect haemagglutination technique according to Neter. 120 of these neonates with no evidence of infection served as controls. 6 out of 8 children with proven E. coli septicaemia had either raised titres or significant rises in titre. Five further neonates with septicaemia, four due to Klebsiella and one to Pseudomonas, had pathologically raised titres as well. 8 out of 12 neonates with clinically suspected septicaemia in whom no pathogen was isolated from the blood or cerebrospinal fluid had raised antibody titres. Following premature rupture of the membranes 2 out of 3 neonates who subsequently developed proven E. coli septicaemia had raised antibody titres against E. coli even on the first day of life. These results suggest that the measurement of antibody titres can be a valuable aid to the diagnosis of neonatal septicaemia.


Mutation induction with UV- and X-radiations in spores and vegetative cells of Bacillus subtilis.

Spores and vegetative cells of Bacillus subtilis strains with various defects in DNA-repair capacities (hcr-, ssp-, hcr-ssp-) were irradiated with UV radiation or X-rays. Induced mutation frequency was determined from the observed frequency of prototrophic reversion of a suppressible auxotrophic mutation. At equal physical dose, after either UV- or X-irradiation, spores were more resistant to mutations as well as to killing than were vegetative cells. However, quantitative comparison revealed that, at equally lethal doses, spores and vegetative cells were almost equally mutable by X-rays whereas spores were considerably less mutable by UV than were vegetative cells. Thus, as judged from their mutagenic efficiency relative to the lethality, X-ray-induced damage in the spore DNA and the vegetative DNA were equally mutagenic, while UV-induced DNA photoproducts in the spore were less mutagenic than those in vegetative cells. Post-treatment of UV-irradiated cells with caffeine decreased the survival and the induced mutation frequency for either spores or vegetative cells for all the strains. In X-irradiated spores, however, a similar suppressing effect of caffeine was observed only for mutability of a strain lacking DNA polymerase I activity.


Some effects of health insurance in Canada--from private enterprise toward public accountability.

Ten years after the introduction of national medical insurance in Canada, it is possible to view the effect of a comprehensive health-insurance program on the relations among physicians, society and government. With costs of health care paid from the public rather than the private purse, provincial efforts to control the cost of hospital and physician services are increasing, and various methods for cost containment are now visible. Since the budget for these expenses is publicly debated it competes for support against other publicly funded programs. The federal/provincial insurance system is evolving as an instrument of reform in the organization of health services and has led to the introduction of legislation that is changing the health-delivery system. A gradual shift in power between various health agencies, physicians, professional organizations and government is occurring.


Consumer-choice health plan (first of two parts). Inflation and inequity in health care today: alternatives for cost control and an analysis of proposals for national health insurance.

The financing system for medical costs in this country suffers from severe inflation and inequity. The tax-supported system of fee for service for doctors, third-party intermediaries and cost reimbursement for hospitals produces inflation by rewarding cost-increasing behavior and failing to provide incentives for economy. The system is inequitable because the government pays more on behalf of those who choose more costly systems of care, because tax benefits subsidize the health insurance of the well-to-do, while not helping many low-income people, and because employment health insurance does not guarantee continuity of coverage and is regressive in its financing. Analysis of previous proposals for national health insurance shows none to be capable of solving most of these problems. Direct economic regulation by government will not improve the situation. Cost controls through incentives and regulated competition in the private sector are most likely to be effective.


Consumer-Choice Health plan (second of two parts). A national-health-insurance proposal based on regulated competition in the private sector.

Medical costs are straining public finances. Direct economic regulation will raise costs, retard beneficial innovation and be increasingly burdensome to physicians. As an alternative, I suggest that the government change financial incentives by creating a system of competing health plans in which physicians and consumers can benefit from using resources wisely. Main proposals consist of changed tax laws, Medicare and Medicaid to subsidize individual premium payments by an amount based on financial and predicted medical need, as well as subsidies usable only for premiums in qualified health insurance or delivery plans operating under rules that include periodic open enrollment, community rating by actuarial category, premium rating by market area and a limit on each person's out-of pocket costs. Also, efficient systems should be allowed to pass on the full savings to consumers. Finally, incremental changes should be made in the present system to alter it fundamentally, but gradually and voluntarily. Freedom of choice for consumers and physicians should be preserved.


[Responses of neurons of hypothalamic nuclei to stimulation of the frontobasal regions of the neocortex].

Neuronal responses of different hypothalamic nuclei to frontobasal cerebral cortex (proreal, posterior orbital, basal and temporal regions) were studied in acute experiments on cats narcotized by membutal mixed with chloraloze. Neurons which could be activated antidromically during stimulation of another region were recorded. On the basis of their response a number of neuronal chains (circles) functioning in forebrain was distinguished. The first chain is orbital gyrus--preoptical zone--proreal gyrus. The second chain has the same cortical components as the first one, but switching over in the hypothalamus takes place in the region of mamillary bodies. The third chain is basal temporal cortex--lateral hypothalamus--prefrontal cortex.


[Participation of corticofugal transmissions in the formation of somatic evoked potentials in the caudate nucleus of monkeys].

Evoked potentials in monkey (Macaca rhesus) nucleus caudatus (chronic experiments) were facilitated when the peripheral stimuli were combined with the electrical stimulation of the cortex in the zone of the sensory projection of the stimulated extremities. These results suggest that the specialized somatic response is formed in n. Cd. by the ascending afferent volley and corticofugal one evoked by the same peripheral stimulus.


Proglonged epileptic twilight states: continuous recordings with nasopharyngeal electrodes and videotape analysis.

Confusion, speech arrest, automatic behavior, and amnesia characterize the prolonged twilight states of both petit mal and psychomotor status. However, in psychomotor status two electroclinical phases were differentiated: (1) A continuous twilight state with partial responsiveness and reactive automatisms interrupted by (2) staring, total loss of responsiveness, and stereotyped automatisms. During the first phase, with reactive behavior, the EEG showed bilateral diffuse slowing. During the second phase, with stereotyped automatisms, there were spreading right temporal 4- to 12-Hz discharges. Petit mal status had one continuous twilight state, during which both stereotyped and reactive automatisms merged as 1.5- to 4-Hz spike-wave complexes, and bimedial temporal 4-Hz discharges' appeared in the EEG.


Marchiafava-Bignami disease.

Marchiafava-Bignami disease was diagnosed postmortem in a 39-year-old man who drank excessive amounts of white port wine. This is the fifth report of the disease in a native North-American with no Italian ancestry. The lesion involved the corpus callosum and hippocampal commissure but spared the anterior commissure, middle cerebellar peduncles, optic chiasm, and centrum semiovale. Wernicke-Korsakoff encephalopathy and pellagroid neuronal changes were also present.


Listeria monocytogenes meningitis: case report.

A case of Listeria monocytogenes septicaemia with meningitis is described. Predisposing factors in this case included chronic liver disease, diabetes mellitus and liver malignancy. The infection responded poorly to ampicillin.


Reduced dose of Rh immunoglobulin following first trimester pregnancy termination.

The efficacy and safety of a 50-microgram dose of Rh immune globulin for prevention of Rh isosensitization following first trimester vacuum abortion are evaluated in this study. A total of 1027 women undergoing abortion at three outpatient facilities participated in the study; 755 (73.5%) completed follow-up serologic screening 6 months after termination of pregnancy. None showed serologic evidence of Rh sensitization at the time of followup. No serious adverse reactions to the drug were observed.


Gingival response to silk, cotton, and nylon suture materials.

Silk, cotton, and nylon suture materials were implanted in the tunica propria of the gingiva in seven adult rhesus monkeys. The histologie study of twenty-four biopsy specimens indicated that there was neither an increase in the vascular permeability nor a leukocytic margination and migration into the tissues adjacent to the suture materials. However, there was a variable histiocytic reaction, with multinucleated cell formation. This reaction was quite intense with cotton, less intense with silk, and practically absent with nylon. The greater cellular response to cotton was probably due to its more active capacity for modifying the internal biologic medium of the gingvia.


Cheek mucosa response to silk, cotton, and nylon suture materials.

The cheek mucosa reacted to the implantation of cotton and silk with an aseptic inflammatory exudate which was found 24 hours and 4 days postoperatively. The leukocytic infiltrate was followed by a histiocytic reaction. Which was established at 7 days but which later progressively declined. The comparison of these findings with those previously obtained from gingival tissues revealed that the leukocytic infiltration in the gingiva was minimal or nonexistent. Probably, the difference in the leukocytic reacting capacity of the gingiva and cheek mucosa was due to the different histologic architecture present in both tissues and directly related to the active capacity of the suture materials to modify the internal biologic medium.


Tissue reactions following apical plugging of the root canal with dentin chips in monkey teeth subjected to pulpectomy.

The tissue reaction following apical plugging of the root canal with dentin chips in monkey teeth subjected to pulpectomy was studied. The reaction was characterized by formation of a cementum-like tissue onto the chips, often walling off the root canal as well as accessory and lateral canals. Twenty-two of twenty-four teeth were rated as successful 95 days after pulpectomy. In the control groups, in which apical plugging of the canal with dentin chips was not attempted, ten of twenty-one teeth were rated as successful at this observation time. In six of the ten successfully treated teeth in these groups a dentin chip plug had been made, although care had been taken to avoid this. It is suggested that a plug of dentin chips is well tolerated by the tissues and may present an effective barrier in the apical part of the root canal, facilitating the accomplishment of a well-condensed, tightly sealing root filling.


Dental pulp reaction to Cavit temporary filling material.

Seventy-two teeth in three Macaque fasicularis monkeys were used to evaluate pulpal response to cavit. Displacement of odontoblastic nuclei was evaluated histologically at three time periods in order to identify initial, early, and final responses. There were no statistically significant differences in pulpal response between Cavit and the zinc oxide-eugenol controls when used in accordance with the manufacturer's directions.


Cerebellar contribution to oculomotor function.

Normal 38 juvenile rhesus monkeys were used to study cerebellar contribution to oculomotor function. (1) Gaze nystagmus was seen only after bilateral flocculus lesions. (2) Spontaneous nystagmus was observed after nodulus, flocculus and cerebellar nuclei lesions. (3) OKN was severely impaired after bilateral flocculus and nodulus lesions. It was slightly impaired after dentate nucleus lesions in a long-term observation. (4) It is a very interesting finding that OKN is severely impaired after destruction of the flocculus and nodulus which have a very important role in the visual fixation.


Morquio's disease and the hearing organ.

Histopathologic evidence offered by a case of Morquio's disease and observed in the hearing organ showed widespread collagen damage, possibly initiated by the general hemorrhageous tendency, while the family history bore evidence of a genetic source. The clinical manifestations comprise striking dwarfism, beaking of the lumbar spine, sternal bulging, flaring of the rib cage, falt vertebrae, marked osteoporosis, prominent joints, semi-crouching stance, short nose. Roentgenograms showed retarded ossification.


Antibody dependent cell-mediated cytotoxicity against Trypanosoma cruzi.

This paper describes in vitro antibody dependent cytotoxicity against Trypanosoma cruzi epimastigotes by normal mouse splenic lymphocytes. Cytotoxicity was expressed as the percentage reduction in the number of motile parasites upon incubation with lymphocytes at 37 degrees C in a defined medium. Failure of the non-motile parasites to regain motility and their ensuing degeneration of 28 degrees C in liver infusion tryptose (LIT) medium confirmed loss of motility as a criterion of cytotoxicity. Incubation of T. cruzi cruzi at 37 degrees C for 18 h in a defined medium per se did not interfere with motility but was followed by a lag phase of the growth curve in LIT medium at 28 degrees C. The lag phase was prolonged for T. cruzi which had previously been incubated at 37 degrees C in the absence of cells.


[The evolutionary historical (phylogenetic) background of the wisdom-tooth problem].

The almost ubiquitous wisdom tooth problem of modern man is in the present paper made the object of an analysis and evaluation on a comprehensive biological basis. It is pointed out that a number of fundamental traits of human cranio-facial evolution have implied developmental trends which have ultimately placed them at the bottom of the later wisdom tooth problem. These aspects are particularly associated with the discrepancy between the size of the jaws and the dental apparatus, arising by failing coordination in the tempo of regression of the separate masticatory elements during the phylogenetic process. The wisdom tooth problem, however, has not become manifest and acute until the present age, with the marked reduction of masticatory function which has taken place.


[Subacute bacterial endocarditis due to lactobacillus (author's transl)].

The case described is one of endocarditis due to lactobacillus casei in a 33-year-old man with aortic insufficiency of undetermined origin. The clinical signs were neurological, following thrombosis of the right posterior cerebral artery. The source of injection was a dental extraction. This case, with a typical clinical picture, is the eleventh to be reported in the literature.


Gonorrhea: unmasking asymptomatic or atypical infection.

Diagnosing a typical case of gonorrhea presents no problem. However, because of the large number of asymptomatic female carriers of the disease, it is mandatory that most sexually active women have routine cultures of urethral and cervical specimens for Neisseria gonorrhoeae. The possibility of gonorrheal infection in the anal canal and, in some cases, the oropharynx must also be considered.


Case report: Recurrent postictal pulmonary edema.

A 32-year-old man with a long history of grand mal seizures but otherwise good health had recurrent episodes of postictal pulmonary edema when he failed to take anticonvulsant medication regularly. This case illustrates most of the features observed in other reported cases of postictal pulmonary edema. Symptoms include dyspnea and cough with production of various quantities of mucoid fluid that may be copious and frankly hemorrhagic. Blood pressure is normal, and temperature may be normal also but is frequently elevated to 100 or 101 F. No cardiac irregularities are heard on auscultation, and the ECG is often normal, but a wide range of abnormalities may be seen. Considerable arterial hypoxemia may occur, and leukocytosis (11,000 to 14,000 cells per cubic millimeter) is common. Rales and rhonchi are audible, and chest films often show bilateral upper and middle lobe infiltrates. The patient is usually clinically improved within 24 hours and the pulmonary edema completely cleared in three to five days.


Effect of photoperiod on the diurnal periodicity of Leucocytozoon smithi gametocytes in the peripheral blood of domestic turkeys.

The daily cyclical variation in Leucocytozoon smithi gametocyte numbers in the peripheral blood of domestic turkeys was shifted 12-hr. by exposure of hosts to a reversed photoperiod. Peak parasitemia coincided with the midpoint of the artificial light period (0100 hr.), while low parasitemia occurred between 1300 hr. and 1700 hr. Disruption of strict gametocyte periodicity was suggested by results of birds exposed to light varying in intensity from 700 lux during the day to 161 lux at night although marked fluctuations in gametocyte numbers occurred.


Retention and excretion of polychlorinated biphenyl residues by laying hens.

Commercial polychlorinated biphenyl (PCB) mixtures with 21, 32, 42, 48, 54, and 68% chlorine were fed to caged White Leghorn hens at 20 p.p.m. for nine weeks. The 42, 48, and 54% mixtures were also fed at 2 p.p.m. Residues in egg at nine weeks were 0.7, 2.4, 14.4, 9.3, 11.4, and at 21.5 p.p.m. for the 21, 32, 42, 48, 54, and 68% chlorine PCBs, respectively. Corresponding values in body fat were 24.0, 51.1, 89.3, 90.5, 124.5, and 52.4 p.p.m., respectively. Levels in eggs and body fat of groups fed 2 p.p.m. were approximately one-tenth the levels in the 20 p.p.m. group. After seven weeks of control feed, the values for the 20 p.p.m. groups were 0.7, 1.8, 2.8, 3.0, 7.2, and 1.8 for eggs and 8.1, 22.4, 26.4, 39.8, 91.7, and 43.6 for body fat. Estimated recovery of consumed PCBs increased from 8% to 55% as chlorine increased from 21 to 68%. Residues in excreta was about 10% of intake for all PCBs. Body fat retention was greater than egg elimination for 21 through 48% chlorine PCB, about the same for 54% and much less for the 68% chlorine PCB. The ratio of egg: fat residue in contaminated birds was .084:1.


The effect of various antifungal agents on aflatoxin production and growth characteristics of Aspergillus parasiticus and Aspergillus flavus in liquid medium.

Various antifungal agents were added to a medium of 2% yeast extract-4% sucrose. Spores of a toxigenic strain of Aspergillus parasiticus were inoculated into the medium and incubated at 26 degrees C. for 10 days. Growth of the mold and aflatoxin formation were monitored every 48 hours during the experiment. Of the antifungal agents evaluated, propionic acid and crystal violet were the most effective compounds in retarding mold growth. Propionic acid was fungicidal at concentrations greater than 3.0 microgram/ml. whereas crystal violet exhibited a mold retarding activity at levels greater than 2,0 microgram/ml. Crystal violet retarded the growth rate of the mold during the initial stages of growth, however, this retardation was overcome after 10 days of incubation. Crystal violet also retarded aflatoxin production and sporulation of Aspergillus parasiticus; however, aflatoxin production was the most sensitive parameter. A survey involving 12 toxigenic isolates of A. parasiticus and A. flavus indicated that these species vary markedly in susceptibility to crystal violet.


A rapid and effecient method for the isolation of proteins from polyacrylamide cells.

A procedure is described for the rapid and efficient electrophoretic elution of protein from polyacrylamide gels which is then collected in a dialysis bag tied to the end of a tube containing the gel slices. To illustrate the method a heterogeneous preparation of alkaline phosphatase was used from which a single homogeneous component was isolated in six hours with a recovery of 86%. The eluted protein is collected in a volume which can easily be kept below 1.5 ml, thus eliminating the need for subsequent concentration. The method has also been used successfully in two other systems in which a human lung tumor-associated antigen and glycogen synthetase from yeast were isolated. Since the method utilizes a standard analytical gel electrophoresis apparatus with no modifications or accessories, it should be immediately applicable for the isolation of many different proteins from polyacrylamide gels.


On the evolution of beta-galactosidase.

The amino acid sequence of beta-galactosidase (beta-D-galactoside galactohydrolase, EC 3.2.1.23) has been compared to itself and to other proteins. Two segments, each of about 380 amino acids, comprising the first three-fourths of the polypeptide chain, were found to be very similar to each other. It is concluded that they are homologous. The carboxyl-terminal fourth has a high percentage of amino acid identities with dihydrofolate reductase of Escherichia coli, suggesting these sequences also are homologous. A model for the origin of beta-galactosidase is presented. The overall similarity of beta-galactosidase to lac repressor does not appear to be significant.


Coupling of lac mRNA transcription to translation in Escherichia coli cell extracts.

In an extract containing all the components for lac gene expression except washed ribosomes, lac mRNA formation was increased 4- to 6-fold by the addition of washed ribosomes. The formation of beta-galactosidase mRNA and enzyme showed very different dependency on added ribosomes. Enzyme was formed in proportion to the number of ribosomes added, whereas 10% of the standard level of ribosomes promoted full levels of transcription. Consistent with their action in vivo, chloramphenicol and erythromycin blocked the ribosome-dependent lac transcription. The same inhibition was seen with RNA pulse-labeled for 1 or 5 min, so that the effect was truly a blockage of formation rather than an increased hyperlability of nascent mRNA. The effect was specified for some RNA species, as it is in vivo: phage lambda N gene transcription was increased rather than inhibited in the presence of chloramphenicol. Chloramphenicol did not stop lac transcription as a result of its blockage of formation of the regulatory nucleotide tetraphosphate (ppGpp), because addition of the nucleotide did not restore mRNA formation in chloramphenicol-treated extracts. Rather, the data are consistent with the ideas that one or a few ribosomes moving closely behind RNA polymerase can prevent its arrest and that, when ribosome movement is blocked by chloramphenicol, the RNA polymerase is exposed to factors that provoke premature RNA chain termination.


Action of corticosteroids in regulation of prostaglandin biosynthesis in cultured fibroblasts.

Various vasoactive agents (e.g., thrombin and bradykinin) and serum stimulate arachidonate production and thus prostaglandin biosynthesis in cultured fibroblasts. Treatment of 3T3 cells with the anti-inflammatory steroid, dexamethasone, inhibits this stimulation but has no inhibitory effect on the basal activity of phospholipase (or on prostaglandin content) in resting, confluent fibroblasts. In intact cells, the proportion of released arachidonic acid converted into prostaglandins is increased by steroid treatment, in quiescent, dense cells and in serum-treated cells, the total incorporation into prostaglandins is increased. Furthermore, the cyclo-oxygenase activity of homogenates from steroid-treated cells is increased very substantially. Thus, although steroids may affect phospholipase (EC 3.1.1.1.4) activities it is possible that these effects may be secondary to a more important stimulatory effect on cyclo-oxygenase activity which leads to selective alterations in prostaglandin biosynthesis. The steroid-induced increase in cyclo-oxygenase activity is not observed in a transformed variant of the same cell line. Fatty acid lipoxygenase (EC 1.13.11.12) activity exists in the particulate rather than the cytosolic fraction of 3T3 cells.


Combined immunofluorescence and high-voltage electron microscopy of cultured mammalian cells, using an antibody that binds to glutaraldehyde-treated tubulin.

An antibody against tubulin that binds specifically to microtubules in glutaraldehyde-fixed cells has been prepared. Sodium dodecyl sulfate-denatured tubulin treated with glutaraldehyde was used to immunize rabbits. In glutaraldehyde-fixed cells the fluorescent image of this antibody reveals a fine lattice of microtubules around the nucleus of PtK1 (Potorous tridactylis) cells and many uniformly fluorescent microtubules in the peripheral cytoplasm. In cells fixed with formaldehyde the microtubules appear to have a similar distribution, but the fluorescent image is much less uniform. Combined high-voltage electron microscopy and immunofluorescent studies reveal that microtubules are found in the cytoplasm in the same region as the fluorescent antibody stain.


Immunoglobulin light chain mRNA is processed from large nuclear RNA.

Recombinant DNA probes, produced by the molecular cloning of immunoglobulin kappa light chain mRNA, have been used to analyze heterogenous nuclear RNA for presumptive precursors to cytoplasmic kappa light chain mRNA, Three discrete classes of nuclear RNA containing kappa mRNA sequences were detected after pulse-labeling of immunoglobulin-producing P3 myeloma cells. Two of these were substantially larger than kappa mRNA (approximately 10 and 4 times larger); the third was similar in size to kappa mRNA. Beginning with the largest, the sequential appearance of these three classes of nuclear RNA preceded the first appearance of newly synthesized kappa light chain mRNA in the cytoplasm. The results presented here suggest that immunoglobulin kappa light chain mRNA is generated by the stepwise cleavage and processing of a large nuclear RNA transcript.


[18F]fluoro-dopa, an analogue of dopa, and its use in direct external measurements of storage, degradation, and turnover of intracerebral dopamine.

3,4-Dihydroxy-5-fluorophenylalanine, fluorodopa, was injected into rats in which unilateral lesions of the nigrostriatal pathway had been made. The rats rotated towards the side with the lesions, thus providing further evidence that fluoro-dopa is an analogue of dopa. [(18)F]Fluoro-dopa was then injected intravenously into fully conscious baboons. A well-collimated scintillation detector, aligned along the occipitomental axis, recorded the accumulation of (18)F in the brain. Control animals accumulated (18)F continuously for 100 min. This accumulation represents net transport of [(18)F]fluoro-dopa from blood to brain, decarboxylation to [(18)F]fluoro-dopamine, storage, and degradation of [(18)F]fluoro-dopamine. alpha-Methyl-dopa, a competitive inhibitor of dopa transport and decarboxylation, prevented the accumulation of (18)F; reserpine, known to release stored intracerebral dopamine, discharged (18)F; pargyline, a monoamine oxidase inhibitor, and haloperidol, a known augmentor of intracerebral dopamine turnover, increased the rate of accumulation of (18)F. These changes in the accumulation of intracerebral (18)F, after [(18)F]fluoro-dopa, were commensurate with the known action of the drugs used to induce them and demonstrate the use of a gamma-emitting precursor of a neurotransmitter to monitor simply, atraumatically, and externally the intracerebral metabolism of the transmitter in fully conscious primates. When applied to man, the same technique should be able to provide more conclusive evidence than is presently available for the role of catecholamines in schizophrenia and depression. It should also provide further insight into the natural history of nigrostriatal diseases and the action of drugs used in their treatment.


Species specificity of cholecystokinin in gut and brain of several mammalian species.

Immunoreactive intact cholecystokinin and its COOH-terminal octapeptide are found in brain as well as in extracts of gut of the monkey, dog, and pig, by using an antiserum with equivalent sensitivities for detecting the octapeptide in free form or incorporated in the intact molecule. The failure to detect intact cholecystokinin in extracts from monkey or dog by using an antiserum developed by immunization with porcine cholecystokinin is presumed to be due to marked species differences in the NH2-terminal portion of the molecule. Tryptic digestion converted the intact cholecystokinin from all species to a peptide resembling the COOH-terminal octapeptide. The amount of cholecystokinin in the brain is comparable to that found in the gastrointestinal tract, the traditional site for this peptide.


Utilization of a depsipeptide substrate for trapping acyl-enzyme intermediates of penicillin-sensitive D-alanine carboxypeptidases.

The penicillin-sensitive D-alanine carboxypeptidases of Bacillus subtilis, Escherichia coli, and Staphylococcus aureus catalyzed the hydrolysis of the D-lactic acid residue from the depsipeptide diacetyl-L-lysyl-D-alanyl-D-lactic acid. The ester substrate was hydrolyzed faster than the peptide analogue, diacetyl-L-lysyl-D-alanyl-D-alanine, by the B. subtilis (15-fold) and E. coli (4-fold) carboxypeptidases, presumably because acylation (k(2)), which is the rate-limiting step of the peptidase reaction, occurred more rapidly during cleavage of the ester bond than during cleavage of the amide bond. No rate acceleration was observed with the S. aureus carboxypeptidase for which deacylation (k(3)) is already the rate-determining step with the peptide substrate. The efficiency of utilization of the depsipeptide (V(max)/K(m)) was greatly enhanced (19- to 147-fold) for all three enzymes. After incubation of the B. subtilis carboxypeptidase and [(14)C]diacetyl-L-lysyl-D-alanyl-D-lactic acid at pH 5.0 and lowering of the pH to 3.0, a radioactive acyl-enzyme intermediate containing 0.43 mol of substrate per mol of enzyme was isolated by Sephadex G-50 chromatography. After acetone precipitation, the acyl group of the denatured acyl-enzyme complex appeared to be bound to the protein by an ester bond. Acyl enzymes were also detected for the S. aureus and E. coli carboxypeptidases after sodium dodecyl sulfate/polyacrylamide gel electrophoresis and fluorography of enzyme incubated with [(14)C]depsipeptide and precipitated with acetone.


Effects of d-amphetamine and ethanol on responding of squirrel monkeys maintained under fixed-ratio schedules of food presentation and stimulus-shock termination.

Effects of d-amphetamine and ethanol were assessed on comparable behaviors maintained under fixed-ratio schedules of either food presentation or termination of electric shock and an accompanying visual stimulus. Ethanol affected the behaviors similarly in all important aspects; d-amphetamine increased rates of responding maintained by stimulus-shock termination at doses that did not affect rates of food-maintained responding. The increases in responding maintained by stimulus-shock termination were not solely due to decreases in the pause prior to the initiation of responding.


The day hospital: structures and functions.

This paper discusses the types of function a day hospital may serve and the choice between generalization and specialization in the creation of day-hospital structures. We suggest that a day hospital may serve as (1) an alternative to hospitalization or to shorten hospital stay; (2) as a long-term resocialization experience; and (3) as an intense brief therapy environment. The patient selection, goals, location, and staffing patterns most appropriate to each of these functions are discussed.


Cholinergic inhibition of methylphenidate-induced stereotypy: oxotremorine.

Lethality of orally administered oxotremorine for female mice required 250 times the dose that was effective for inhibiting methylphenidate-induced stereotypy. A number of lines of evidence indicate that increasing central cholinergic activity may be useful in various psychiatric syndromes and movement disorders. A relatively safe oral cholinomimetic would be clinically useful. Oxotremorine may be such an agent.


Effect of diazepam on food consumption in rats.

Diazepam significantly increased milk consumption in rats that had never been exposed to this food before but not in rats trained to drink milk. Diazepam failed to increase lever-pressing for food reward except when this behavior had been previously suppressed by the simultaneous administration of electric shock. These data suggest that diazepam does not alter appetite, but enhances the expression of motivation suppressed by instinct or training.


Circadian rhythm of lithium toxicity in mice.

The existence of cyclical (circadian) variations in lithium toxicity in mice was determined. Mice, standardized to a light-dark cycle, were injected with lithium chloride (940 mg/kg) at one of six times (20:00, 24:00, 4:00, 8:00, 12:00, and 16:00) and subsequently observed for mortality over 28 h. A significant (P less than 0.01) time-of-day effect was found for lithium-induced lethality, with highest lethality following injection at 12:00.


Time course effects of marijuana and ethanol on event-related potentials.

Twelve male college students received orally on different days NIMH marijuana extract calibrated to contain 0.7 mg/kg delta-9-tetrahydrocannabinol, 1.0 ml/kg 95% ethanol, and placebo in a double-blind balanced-order design. The contingent negative variation (CNV), auditory evoked potential (EP), heart rate (HR), and subjective measures of intoxication were recorded prior to drug ingestion and at regular intervals for 4.5 h postdrug. Both drugs produced significant subjective effects. Marijuana increased HR but did not have a significant effect on CNV amplitude or EP peak amplitudes and latencies. Ethanol increased HR, but not significantly, and reduced CNV amplitude and N1-P2 amplitude. Time-action curves for ethanol's effect on subjective high, HR, and N1-P2 amplitude were parallel, peaking between 0.5 and 1.5 h postdrug and returning to baseline by the end of testing. Time-action curve for ethanol's effect on the CNV showed continuing amplitude reduction throughout the test session.


The attenuation of a specific cue-to-consequence association by antiemetic agents.

Previous research has been shown that rats develop a conditioned taste aversion after a single pairing of a distinct taste and subsequent toxicosis. The experiments reported here test the hypothesis that the expression of a taste aversion may reflect classically conditioned nausea mediated by activation of brainstem emetic centers by taste stimuli. Rats were allowed to drink a saccharin solution (1 g/l) and 10 min later were intubated with LiCl (180 mg/kg) to produce nausea. When control rats were posttested for saccharin preference they consumed less than 50% of their pretest intake. Experimental rats were injected with one of four pharmacologically distinct antiemetic drugs 30 min prior to their posttest with saccharin. Each drug significantly attenuated the aversion to saccharin at one dose level. The antiemetic drugs we used were scopolamine HBr, cyclizine, prochlorperazine dimaleate, and trimethobenzamide. These drugs had no effect on the conditioned fear of a noise that signaled foot shock or on a natural aversion to a bitter fluid (quinine monohydrochloride, 100 mg/l). Our data suggest that pharmacological suppression of the neural mechanisms of emesis selectively disrupts conditioned taste aversions, and that moderate dose levels are critical for obtaining this effect.


On the interaction of drugs with the cholinergic nervous system. I. Tolerance to phencyclidine derivatives in mice: pharmacological characterization.

Phencyclidine [1(1-phenylcylohexyl) piperidine] and cyclohexamine [1(1-phenylcyclohexyl) ethylamine) were used as model psychotropic drugs to study the phenomenon of tolerance in mice. The behavioral effects of these drugs were measured by forced motor activity using the rotarod test. Tolerance develops progressively with chronic treatment at a rate and to a degree that are dose-dependent. The optimal conditions for tolerance induction are s.c. administration with 4-h intervals. The process of tolerance development is expressed in concomitant changes in five indices chosen for its quantification: ED50 values, duration, duration-dose dependency, critical falling time, and body weight. All these changes were found to be totally reversible, with no carry-over between two consecutive tolerance cycles. It was established that cyclohexamine is a better tolerance-inducer than phencylidine, although the nature of the tolerance developed for both drugs is qualitatively similar.


On the interaction of drugs with the cholinergic nervous system. II. Cross-tolerance between phencyclidine derivatives and cholinergic drugs.

A symmetrical cross-tolerance was found between two phencyclidine derivatives--phencyclidine and cyclohexamine--and also between two cholinergic drugs--physostigmine and oxotremorine. On the other hand, mice rendered tolerant to the phencyclidine derivatives showed cross-tolerance to these cholinergic drugs, but no cross-tolerance was observed in the opposite direction. The applicability of such experiments to the elucidation of neurochemical interactions of centrally acting drugs is discussed.


A comparison of the food intake suppression produced by giving amphetamine as an aversion treatment versus as an anorexic treatment.

Separate groups of rats were given either 1 or 2 mg/kg injections of amphetamine 30 min before or after eating a preferred high-fat food. When given before eating as an anorexic treatment, amphetamine initially suppressed intake almost completely, but with repeated injections tolerance developed. In contrast amphetamine given after eating as an aversion treatment initially had little effect on intake, but with repeated injections it suppressed intake almost completely in rats receiving the higher dose.


Genotype and test experience determine responsiveness to morphine.

Initial responsiveness to morphine was studied in two inbred strains of mice, C57BL/6J and DBA/2J, and their F1 hybrid, using both a hot-plate analgesia test and a locomotor-activity test. Three dose levels of morphine were used, 0 mg/kg 5 mg/kg, and 15 mg/kg. The inclusion of the 0 mg/kg group revealed differences between the inbred strains in the effects of test experience. These data also led to some new conclusions about the differences in responsiveness to morphine between the strains studied. On both tests, the DBA mice showed no effect of morphine, the C57 mice showed large effects, and the F1 mice showed an intermediate effect.


Clozapine in tardive dyskinesia.

Clozapine, which has had limited clinical testing in the U.S.A., was evaluated in 12 chronic schizophrenic patients with tardive dyskinesia. Its antipsychotic activity was again demonstrated and it suppressed the symptoms of tardive dyskinesia with a marked rebound occurring in these symptoms when it was withdrawn; there was no rigidity or other Parkinsonian symptoms. However, out of a total of 12 patients, neutropenia (800 and 1120) occurred in two patients, convulsion in one patient, marked withdrawal effects in three patients, and a hypotensive collapse with atrial fibrillation in one patient. If these adverse effects are confirmed in a larger sample size, then despite the novel desirable effects of clozapine it would seem unlikely that it will gain widespread or routine use.


Marijuana, alcohol, and combined drug effects on the time course of glare recovery.

The time course of light adaptation after intense light exposure is significantly delayed by alcohol, marijuana, and a combined dose of alcohol and marijuana. These effects were found in a double blind experiment, using 10 subjects. The experimental treatments were placebo, 0.75 ml/kg of 95% ethanol, 8 and 15 mg of delta9 tetrahydrocannabinol (THC). and 0.75 ml/kg of 95% ethanol together with 15 mg of THC. The marijuana-induced delay in recovery is doserelated. Both drugs produce delayed recovery for at least 2 h after drug ingestion. The combined alcohol and marijuana treatment produces little more than the effect produced by either drug alone, suggesting some antagonism between the drugs--a suggestion supported by a significantly lower blood alcohol level for the alcohol dose when combined with marijuana than when taken alone.


Screening hallucinogenic drugs II. Systematic study of two behavioral tests.

The effects of hallucinogenic and nonhallucinogenic drugs were studied on two behavioral tests: (1) discriminated Sidman avoidance, using modified Bovet-Gatti profiles, which have been proposed as specific in detecting hallucinogenic activity and (2) a drug discrimination experiment. By the first method, the "hallucinogenic profile" was obtained with both hallucinogenic and nonhallucinogenic drugs and, at least as used here, was not a suitable screening method. In the drug discrimination experiment, data from the present study along with other available evidence suggest the potential value of this method for drug screening procedures.


Elevated prostaglandin production in cultured cells from a patient with fibrodysplasia ossificans progressiva.

Prostaglandin E production was measured in cells cultured from both a fibromatoid lesion and a normal area of skin in a patient with fibrodysplasia ossificans progressiva. The synthesis of prostaglandin E-like material (iPGE) was ten- to twenty-fold greater in cells cultured from the patient's fibromatoid lesion than in fibroblasts obtained from her normal skin. Addition of indomethacin in vitro resulted in a greater than 95% reduction of iPGE production in both cell cultures. These observations appear to warrant further investigation in additional patients, with this disease.