Quantitative determination of carbaryl in apples, lettuce, and water by densitometry of thin layer chromatograms.

A method for the quantitative determination of carbaryl insecticide by in situ densitometry was developed. After separation on silica gel thin layer plates, carbaryl residues were detected by using p-nitrobenzenediazonium fluoborate reagent and quantitated by scanning the resultant blue spots with a fiber optics densitometer and comparing them with standards. The method was applied to water fortified with carbaryl at 8 ppb and apples and lettuce fortified at 0.10 ppm; all recoveries were greater than 89%. The 2 crop extracts were cleaned up by using the AOAC thin layer chromatographic method for visual estimation of carbaryl. Related carbamate insecticides were detected by using the same reagent, and the potential for quantitation was demonstrated.


Pathways of assimilation of [13N]N2 and 13NH4+ by cyanobacteria with and without heterocysts.

The principal initial product of metabolism of [13N]N2 and 13NH4+ by five diverse cyanobacteria is glutamine. Methionine sulfoximine inhibits formation of [13N]glutamine except in the case of Gloeothece sp., an organism with a thick sheath through which the inhibitor may not penetrate. Thus, glutamine synthetase appears to catalyze the initial step in the assimilation of N2-derived or exogenous NH4+ by these organisms. [13N]Glutamate is, in all cases, the second major product of assimilation of 13N-labeled N2 and NH4+. In all of the N2-fixing cyanobacteria studied, the fraction of 13N in glutamine declines and that in glutamate increases with increasing times of assimilation of [13N]N2 and 13NH4+, and (Gloeothece again excepted) methionine sulfoximine reduces incorporation of 13N into glutamate as well as into glutamine. Glutamate synthase therefore appears to catalyze the formation of glutamate in a wide range of N2-fixing cyanobacteria. However, the major fraction of [13N]glutamate formed by Anacystis nidulans incubated with 13NH4+ may be formed by glutamic acid dehydrogenase. The formation of [13N]alanine from 13NH4+ appears to be catalyzed principally either by alanine dehydrogenase (as in Cylindrospermum licheniforme) or by a transaminase (as in Anabaena variabilis).


Deoxyuridine residues in DNA of thymine-requiring Bacillus subtilis strains with defective N-glycosidase activity for uracil-containing DNA.

DNA extracted from exponentially growing cells of thymine-requiring Bacillus subtilis strains with defective N-glycosidase activity for deoxyuridine residues in DNA was subjected to the action of N-glycosidase in vitro and analyzed by sedimentation in alkaline sucrose gradients. The sites attacked by N-glycosidase occurred once per 6 X 10(6) to 7 X 10(6) daltons of DNA from cells cultured in the presence of growth-supporting concentrations of thymine. The number of N-glycosidase-susceptible sites increased when the thymine concentration in the medium was lowered. Parallel to this observation, the N-glycosidase-defective mutant cells were less apt to show the detrimental effect due to thymine depletion than were the parental cells. Such sites were not detected in DNA from cells with a normal N-glycosidase activity or with a "wild type" capacity for thymidylate synthesis. The results are interpreted to mean that cells defective for thymidylate synthesis incorporate dUTP in place of TTP in DNA and that the deoxyuridine residues, once incorporated, remain in the DNA in the absence of N-glycosidase activity.


Isolation of TOL and RP4 recombinants by integrative suppression.

We obtained genetic and molecular evidence of non-thermosensitive recombinants of RP4 (Kmr Tcr Cbr/Apr) and the thermosensitive TOL plasmid. As first isolated in Pseudomonas aeruginosa PAO, the recombinant plasmid pTN1 specified noninducible synthesis of TOL enzymes and was transmissible to Escherichia coli on selection for the transfer of kanamycin resistance. The phenotypic expression of TOL genes of pTN1 in E. coli was low and also noninducible. A spontaneous segregant, pTN2, appearing from pTN1, conferred inducible synthesis of TOL enzymes. These plasmids carry all of the TOL determinants as evidenced by the ability of Pseudomonas putida carrying recombinant plasmids to grow on toluene, xylene, and m-toluate. In E. coli the expression of TOL genes with normal regulation (pTN2) appears to be extremely low without induction, and the induced expression is comparable to that with defective regulation (pTN1). The measurement of the molecular weight of pTN2 by electron microscopy gave a value of about 74 X 10(6).


Conjugative plasmids in Neisseria gonorrhoeae.

A conjugation system initially discovered in beta-lactamase-producing gonococci mobilized small non-selftransmissible R plasmids encoding beta-lactamase (penicillinase) production into other gonococci, Neisseria, and Escherichia coli. This conjugation system was mediated by a separate selftransmissible plasmid of 23.9 X 10(6) daltons, pFA2. Conjugative plasmids capable of mobilizing R plasmids were also found in nearly 8% of the non-penicillinase-producing gonococci. These were similar to pFA2 in size, buoyant density, and restriction endonuclease digest patterns but were less efficient than pFA2 in mobilization of the penicillinase plasmid pFA3. The presence of conjugative plasmids in gonococci isolated before the appearance of penicillinase-producing strains indicates that a conjugation system for plasmid transfer predated the appearance of R plasmids in gonococci.


Characterization of Staphylococcus aureus plasmids introduced by transformation into Bacillus subtilis.

Covalently closed circular DNA from five Staphylococcus aureus plasmids has been introduced into Bacillus subtilis. Four of these plasmids (pUB110, pCM194, pSA2100, and pSA0501) have been selected for further study. These plasmids replicate as multicopy autonomous replicons in both Rec+ and Rec- B. subtilis strains. They may be transduced between B. subtilis strains or transformed at a frequency of 10(4) to 10(5) transformants per microgram of DNA. The molecular weights of these plasmids were estimated, and restriction endonuclease cleavage site maps are presented. Evidence is given that pSA2100, an in vivo recombinant of pSA0501 and pCM194 (S. Iordănescu, J. Bacteriol. 124:597-601, 1975), arose by a fusion of the latter plasmids, possibly by insertion of one element into another as a translocatable element. Genetic information from three other S. aureus plasmids (pK545, pSH2, and pUB101) has also been introduced into B. subtilis, although no covalently closed circular plasmid DNA was recovered.


Plasmid-mediated chromosomal gene transfer in Neisseria gonorrhoeae.

An indigenous Neisseria gonorrhoeae conjugative plasmid, pLE2450, was tested for its ability to mediate chromosomal gene transfer between gonococcal strains. Plasmid-mediated chromosomal transfer was detected at a low frequency and can be used to establish certain linkage relationships between amino acid and antibiotic resistance markers.


Deoxycytidylate deaminase from Bacillus subtilis. Purification, characterization, and physiological function.

dCMP deaminase from Bacillus subtilis has been purified 700-fold. In addition to the substrate, dCMP, the enzyme requires dCTP, Zn2+, and 2-mercaptoethanol, Mg2+ cannot substitute for Zn2+. The dCMP saturation curve is hyperbolic in the presence of saturating concentrations of dCTP and Zn2+. The dCTP saturation curve is sigmoidal, the sigmoidicity being dependent on the Zn2+ and dCMP concentrations. The molecular weight as determined by gel filtration is 170,000 both in the presence and in the absence of dCTP and Zn2+. In the absence of thiols, the enzyme is highly unstable. At 0 degrees, the half-life of the enzyme activity is 30 min. Addition of Zn2+ and dCTP protects against this inactivation. In the presence of a thiol, dCTP and Zn2+ protect the enzyme against heat inactivation at 50 degrees. A mutant lacking dCMP deaminase (dcd) was isolated. Labeling of the pyrimidine nucleotide pools reveals that in the parent strain, 45% of the dTTP pool is derived via dCMP deamination, the residual 55% being derived via reduction of a uridine nucleotide. Since the dcd mutant grows with the same doubling time as the parent strain, we conclude that uridine nucleotide reduction alone is capable of supplying sufficient dUMP for normalthymidine nucleotide synthesis.


Enzymatic formation of uridine diphosphate N-acetyl-D-mannosamine.

An enzyme that catalyzes the interconversion of UDP-N-acetyl-D-glucosamine and UDP-N-acetyl-D-mannosamine was purified about 700-fold from the supernatant fraction of Bacillus cereus, and the properties of this enzyme were studied. This enzyme was not stimulated by NAD+, NADH, or any metal ions. The optimum pH was between 7.5 and 8.0. At equilibrium of the reaction, the ratio of UDP-N-acetylglucosamine to UDP-N-acetylmannosmaine was about 9:1. The enzyme was inactive toward free N-acetylhexosamines, their phosphate esters, UDP-glucose, and UDP-N-acetylgalactosamine. A stimulatory role of UDP-N-acetylglucosamine was demonstrated. In the reaction with UDP-N-acetylglucosamine, the rate as a function of substrate concentration showed a sigmoidal relationship with a Hill coefficient of 1.8 and an apparent Km value for UDP-N-acetylglucosamine of 1.1 mM. The reverse reaction with UDP-N-acetylmannosamine required the presence of UDP-N-acetylglucosamine. The UDP-N-acetylglucosamine concentration required for half-maximal activation was about 0.5 mM. The apparent Km for UDP-N-acetylmannosamine measured in the presence of 0.5 mM UDP-N-acetylglucosamine was 0.22mM. Other nucleotides or hexosamine derivatives were not stimulatory. The same activity was found in cell extracts from several bacterial species.


Purification and characterization of saccharopine dehydrogenase from baker's yeast.

Saccharopine dehydrogenase (N6-(glutar-2-yl)-L-ly-sine:NAD oxidoreductase (L-lysine-forming)) from baker's yeast was purified to homogenicity. The overall purification was about 1,200-fold over the crude extract with a yield of about 24%. The purified enzyme had a sedimentation coefficient (S20,w) of 3.0 S. The molecular weight determinations by sedimentation equilibrium, Sephadex G-100 gel filtration, and sodium dodecyl sulfate-polyacrylamide gel electrophoresis gave a value of about 39,000 and, therefore, saccharopine dehydrogenase is a single polypeptide chain enzyme. A Stokes radius of 27 A and a diffusion constant of 7.9 X 10(-7) cm2 s-1 were obtained from Sephadex gel filtration chromatography. The enzyme had a high isoelectric pH of 10.1. The NH2-terminal sequence was Ala-Ala----. The enzyme possessed 3 cysteine residues/molecule; no disulfide bond was present. Incubation of saccharopine dehydrogenase with p-chloromercuribenzoate or iodoacetate resulted in complete loss of enzyme activity. Whereas the coenzyme and substrates were ineffective in protecting from inactivation by p-chloromercuribenzoate, iodoacetate inhibition was protected by excess coenzyme.


Acetylation of the NH2-terminal serine of prostaglandin synthetase by aspirin.

Aspirin (acetylsalicylic acid) inhibits prostaglandin synthesis by acetylating an active site portion of the enzyme, prostaglandin synthetase. In the current study, the site of acetylation has been demonstrated to be a seryl residue at the NH2 terminus of the enzyme. Purified [3H]acetyl enzyme was prepared from seminal vesicle homogenates treated with [acetyl-3H]aspirin. The [3H]acetate to protein bond was stable to hydroxylamine, indicating an N-acetyl linkage. The [3H]acetyl enzyme was fragmented sequentially with cyanogen bromide, trypsin, and pronase. The 3H material isolated from the pronase digest was identified as N-acetylserine. This finding indicates that the oxygenase portion of prostaglandin synthetase has an NH2-terminal serine which is involved in enzymatic activity and is susceptible to acetylation by aspirin.


Calcium-binding proteins in the vorticellid spasmoneme.

The proteins of the contractile spasmoneme from Vorticella convallaria, Carcheslium polypinum, and Zoothamnium geniculatum have been extracted in the detergent, sodium dodecyl sulfate (SDS), as well as urea and guanidine hydrochloride (GuCl). After SDS extraction, the molecular weight distribution of the proteins was examined by means of SDS-polyacrylamide gel electrophoresis. Significant amounts of material corresponding to the contractile proteins actin and tubulin are not present. The contractile organelles in the three species examined contain a group of closely related proteins of molecular weight near 20,000, which constitute a major part (40-60%) of the dry mass. The 20,000 mol wt proteins in Zoothamnium bind calcium with high affinity (pK congruent to 6) and are termed "spasmins." By means of urea polyacrylamide gel electrophorsis, it is demonstrated that in Carchesium and Zoothamnium certain spasmin components bind calcium even in the presence of 6 M urea. The binding of calcium in 6 M urea suggests a functional relationship between the spasmins and the calcium-binding proteins of striated muscle which behave similarly. The calcium binding in urea also indicates that the spasmins within a single spasmoneme have different calcium affinities, and this difference in calcium-binding properties may be an important factor in the physiological function of the organelle.


Plant protoplast agglutination by artificial carbohydrate antigens.

The existence of beta-lectins on protoplast surfaces is confirmed by the agglutination of protoplasts by those Yariv antigens that have sugar specificities which also interact with isolated beta-lectins. Agglutination by beta-maltosyl but not by beta-D-mannosyl Yariv antigens is used to identify some of the structural features required of the ligand for beta-lectin binding. Inhibition of agglutination by phenolic glycosides and the effect of protoplast fixation are also investigated.


Proteins of rough microsomal membranes related to ribosome binding. II. Cross-linking of bound ribosomes to specific membrane proteins exposed at the binding sites.

Two proteins (ribophorins I and II), which are integral components of rough microsomal membranes and appear to be related to the bound ribosomes, were shown to be exposed on the surface of rat liver rough microsomes (RM) and to be in close proximity to the bound ribosomes. Both proteins were labeled when intact RM were incubated with a lactoperoxidase iodinating system, but only ribophorin I was digested during mild trypsinization of intact RM. Ribophorin II (63,000 daltons) was only proteolyzed when the luminal face of the microsomal vesicles was made accessible to trypsin by the addition of sublytical detergent concentrations. Only 30--40% of the bound ribosomes were released during trypsinization on intact RM, but ribosome release was almost complete in the presence of low detergent concentrations. Very low glutaraldehyde concentrations (0.005--0.02%) led to the preferential cross-linking of large ribosomal subunits of bound ribosomes to the microsomal membranes. This cross-linking prevented the release of subunits caused by puromycin in media of high ionic strength, but not the incorporation of [3H]puromycin into nascent polypeptide chains. SDS-acrylamide gel electrophoresis of cross-linked samples a preferential reduction in the intensity of the bands representing the ribophorins and the formation of aggregates which did not penetrate into the gels. At low methyl-4-mercaptobutyrimidate (MMB) concentrations (0.26 mg/ml) only 30% of the ribosomes were cross-linked to the microsomal membranes, as shown by the puromycin-KCl test, but membranes could still be solubilized with 1% DOC. This allowed the isolation of the ribophorins together with the sedimentable ribosomes, as was shown by electrophoresis of the sediments after disruption of the cross-links by reduction. Experiments with RM which contained only inactive ribosomes showed that the presence of nascent chains was not necessary for the reversible cross-linking of ribosomes to the membranes. These observations suggest that ribophorins are in close proximity to the bound ribosomes, as may be expected from components of the ribosome-binding sites.


High-performance liquid chromatographic determination of plasma and urinary 1-ethyl-1,4-dihydro-4-oxo-1,8-naphthyridine-3,7-dicarboxylic acid.

A high-performance liquid chromatographic method for the analysis of 1-ethyl-1,4-dihydro-4-oxo-1,8-naphthyridine-3,7-dicarboxylic acid (I) in plasma and urine is described. A statistical evaluation of the assay technique has shown acceptable accuracy and precision at concentrations as high as 2.0 microgram/ml of plasma or 29.0 microgram/ml of urine for samples augmented with 1. As little as 0.08 microgram/ml of I in plasma or 0.42 microgram/ml of I in urine were quantitatively determined. The mean relative error for the assay of unknown concentrations of I in plasma and urine was +/- 8% and +/- 3%, respectively. This method was used for the analysis of I in the plasma and urine of rhesus monkeys following oral administration of 200 mg/kg of nalidixic acid.


Identification and penicillinase testing of Neisseria gonorrhoeae from primary isolation cultures on modified New York City medium.

The fluorescent-antibody test, rapid carbohydrate utilization test (RCUT), and a test for penicillinase production were performed on the bacterial growth from primary cultures on modified New York City medium. Of 134 gonococcal infections in men, 88.8% were diagnosed by the fluorescent-antibody test and 70.9% by the RCUT after incubation for 24 h; the corresponding figures for 75 infections in women were 86.7 and 54.7%, respectively. After incubation for 48 h, 100% of infections were diagnosed by the fluorescent-antibody test, wherease 88.8% of infected males and 86.7% of females were also diagnosed by the RCUT. Primary isolation cultures on modified New York City medium proved suitable for determining the ability of strains to produce penicillinase by a modified RCUT procedure. The method of isolation and identification by using primary cultures from modified New York City medium is both rapid and economical. The rapidity of diagnosis provided by the RCUT makes this a very useful diagnostic method, particularly in laboratories lacking immunofluorescence equipment. Since the penicillinase production test forms part of a routine identification procedure, no extra culture media or subcultures are required. The rapidity of this test should make it of value in tracing contacts of patients infected with penicillinase-producing strains.


Esculin hydrolysis reaction by Escherichia coli.

The literature contains variable reports concerning the hydrolysis of esculin by members of the family Enterobacteriaceae and particularly Escherichia coli. We examined 113 strains of fresh clinical isolates of E. coli and assessed the ability of colonies in a population to hydrolyze esculin with and without preincubation in inducible substrates at 24, 48, and 72 h. The number of strains capable of fermenting salicin, a sugar with a beta-glucoside linkage like esculin, was studied under the same conditions. A strip test that measured the presence of the constitutive glucosidase was also performed with and without preincubation in inducible substrates. No E. coli strain was able to produce constitutive enzyme; preincubation in esculin and salicin resulted in an induction of the beta-glucosidase. The number of colonies able to hydrolyze esculin increased with time. Only those strains preincubated in esculin or salicin were able to produce a positive constitutive strip test. Because the beta-glucosidase of E. coli is inducible, one should employe, when using growth media, a light inoculum obtained by touching the top of a colony with a bacteriological wire and read the reaction between 18 and 24 h, or perform a rapid strip or spot test.


N. gonorrhoeae: pathogenicity of colonial type 5.

This paper records the results of the intravenous inoculation of chick embryos with type 5 gonococci and establishes that these strains are pathogenic.


Thalamic projections to S-I in macaque monkey.

The organization of thalamic input to functionally characterized zones in primary somatosensory cerebral cortex (S-I) of macaque monkeys (Macaca mulatta) was investigated using the method of labelling by retrograde transport of horseradish peroxidase (HRP). It was found that the cell columns positioned at the posterior margin of the band of cortex representing a given body region receive thalamic input from a posterior level of the ventroposterior thalamic nucleus (VP), and that cell columns at successively more anterior positions within that band receive input from successively more anterior levels of VP. The extreme posterior and anterior margins of the S-I hand, foot and face areas receive input from neuron populations which are not as widely separated in the anteroposterior dimension of VP as the neurons projecting to the extreme anterior and posterior margins of the proximal limb and trunk representations in S-I. These characteristics of the organization of the projections from VP to S-I are consistent with the view that the body representations in VP and S-I have the same connectivity and differential submodality distribution; and with the idea that thalamocortical conncetions only exist between functionally equivalent neuron populations in VP and S-I.


The cerebellofugal projections in the brachium conjunctivum of the rat. II. The ipsilateral and contralateral descending pathways.

The cerebellofugal projections in the ipsilateral and contralateral descending pathways of the brachium conjunctivum (B.C.) in the rat have been investigated in 22 animals using the Fink-Heimer technique to demonstrate the axonal degeneration resulting from complete B.C. lesions (6), partial B.C. lesions (14) and control lesions dorsal to the B.C. (2). The incidental degeneration resulting from the concomitant involvement of the structures surrounding the B.C. is accounted for in terms of known fiber pathways and from the results in the control experiments. This study confirms Ramón y Cajal's ('03) original observation that cerebellofugal fibers in the B.C. project caudally throughout the length of the hindbrain via both ipsilateral and contralateral descending pathways. The fibers forming the ipsilateral descending pathway proceed ventrally from the B.C. at the level of the trigeminal motor nucleus, turn caudally and terminate within nucleus reticularis parvocellularis (Rpa). In particular, fibers within this pathway terminate densely in two cytoarchitecturally distinct Rpa subnuclei--nucleus "k" (Meessen and Olszewski, '49) and a caudal linear subnucleus--which project to the cerebellum (Faull, '77). The contralateral descending pathway (B.C.de) roceeds caudally from the decussation of the B.C. within the ventromedial region of the magnocellular nuclei of the reticular formation of the pons and medulla. Cerebellofugal fibers of the B.C.de terminate in a distinctive pattern within precerebellar brainstem nuclei: densely throughout the middle third of nucleus reticularis tegmenti pontis; in a longitudinal zone of each of the three pontine gray subnuclei; in the principal and dorsal accessory nuclei of the inferior olive; and sparsely within nucleus reticularis paramedianus. Fibers in the B.C.de also terminate within the magnocellular nuclei of the reticular formation, principally the nuclei reticularis pontis oralis and caudalis.


Efferent projections of the subthalamic nucleus: an autoradiographic study in monkey and cat.

The efferent projections of the subthalamic nucleus were studied with the autoradiographic tracing technique in Rhesus monkey and cat. From the data it appears that the major efferent projections of the nucleus are to the pallidal complex and the substantia nigra. In both monkey and cat, the projection to the pallidal complex is truly massive and is directed at both pallidal segments. The projection field includes an infracommissural part of the pallidal complex bordering on the substantia innominata. In the monkey the termination in the pallidal complex is organized in several characteristic bands oriented parallel to the medullary laminae. The subthalamo-pallidal projection in monkey further appears to be topographically organized. The projections to the substantia nigra is prominent in both cat and monkey though not as massive as that to the pallidal complex. The distribution of termination in the substantia nigra favors the more ventral strata near the cerebral peduncle. In the monkey the terminal distribution appears to avoid regions of the substantia nigra containing pigmented neurons and it is suggested that the subthalamo-nigral pathway may prefer non-dopaminergic neurons. In addition to the above major projections, sparse projections were noted to the thalamic nuclei ventralis lateralis and ventralis anterior, to the putamen, and to the mesencephalic nucleus tegmenti pedunculopontinus, pars compacta. The findings are discussed.


The neurons and the synaptic endings in the primate basilar pontine gray.

Two types of neurons, projection and intrinsic, previously identified in Golgi preparations of the adult monkey (Macaca mulatta) basilar pontine gray (Cooper and Fox, '76) were observed electronmicroscopically in Macaca mulatta and the squirrel monkey Saimiri sciureus. The cell body of the projection neuron measures up to 37 micrometer and its cytoplasm is rich in organelles. The Goli apparatus, ribosomes, and mitochondria are disposed around the nucleus, while rough endoplasmic reticulum though abundant is usually confined to one half of the cell body. The cell body of the intrinsic neuron measures less than 20 micrometer and its cytoplasm displays prominent ribosomes, but a paucity of other organelles. Five types of synaptic profiles have been identified in the neuropil of the basilar pons; one measures up to 5 micrometer and the rest 2 micrometer or less. They are: (1) a large profile (MSV) containing medium size vesicles (500A) and a central core of mitochondria and neurofilaments; (2) a profile (SSV) containing small round vesicles (250-500 A) which is the most abundant and ubiquitous; (3) a profile (F) containing flattened or pleomorphic vesicles; (4) a profile (LSV) containing large oval egg shaped vesicles (750 A); and (5) a pale profile (PP) that contains oval and occasionally pleomorphic vesicles. MSV, SSV, and LSV terminals form asymmetrical contacts and F terminals form symmetrical contacts with both dendritic and vesicle-containing, pale profiles. The vesicle-containing, pale profile is both pre- and post-synaptic and participates in serial synapses. Following unilateral cortical ablations both dark and filamentous degeneration were observed in the ipsilateral basilar pontine gray.


The intraosseous orientation of the alveolar component of marmoset alveolodental fibers.

Sections of the jaws from marmosets of all ages were impregnated with silver nitrate to demonstrate the intrabony course of the alveolar fibers of the periodontal ligament. As the interseptal bone undergoes a period of resorption and apposition, the intrabony alveolar fibers also are lost and reformed. Age changes were noted in the insertion depth of the alveolar fibers. A continuum of fibers traversing the alveolar septum could not be determined.


Severe chronic intra-abdominal sepsis: a report of 3 cases and a review of patient management.

The management of three cases (one fatal) with extensive intraabdominal sepsis, is described. Management included metabolic and fluid control, intravenous nutrition (where feeding by the oral route is impossible because of multiple intestinal fistuli), maintenance and support of vital organ function, and infection control. Appropriate and timely surgical intervention may be life saving.


Catheter-induced ascites--an unusual complication of parenteral feeding.

A nearly fatal complication of parenteral feeding is reported. An emaciated infant with severe Shigella dysentery was treated with intravenous feeding through a catheter in the inferior vena cava. After three days severe ascites developed acutely. Venocavography revealed effusion into the peritoneal cavity due to the catheter having penetrated the wall of the inferior vena cava.


Distribution of 14C-formaldehyde after pulpotomy with formocresol.

Pulpotomies were performed on rhesus monkeys with use of formocresol to determine if there was uptake of 14C-formaldehyde into the systemic circulation after formocresol pulpotomies. Five-minute exposure of pulpal tissue to the 14C-formocresol resulted in the systemic absorption of approximately 1% of the dose. Two hours of exposure of pulp tissue to the 14C-formocresol did not increase the systemic absorption. Multiple sequential pulpotomies resulted in proportionately higher systemic absorption of 14C-formaldehyde. Application of 131I to pulpotomy sites indicated that formocresol compromises the microcirculation of the dental pulp. Autoradiography disclosed extensive concentrations of 14C-formaldehyde in the pulp, dentin, periodontal ligament, and bone.


The sensitization of children by opportunist mycobacteria in Lagos, Nigeria.

Groups of school children aged 6-14 years were tested with PPDS and one of the following five antigens simultaneously, namely PPDA, PPDF, PPDG, PPDPL and PPDY, PPDS was prepared from the human tubercle bacillus, and the others were prepared from M. avium, M. fortuitum, the 'Gause' organisms, M. marinum and M. kansasii respectively. It was observed that there was some increase in induration size to PPDA, PPDG, PPDL, PPDS and PPDY with increase in age, while M. fortuitum gave a preponderance of small reactions with no increase of size with age. It was also observed that there was evidence of cross sensitization between PPDS and all the other antigens, particularly in those who had negative or doubtful reactions.


Serological and biochemical relationships between the alleged avirulent variant of Corynebacterium kutscheri and streptococci of group N.

Morphological, biochemical and serological observations suggested that no close relationship existed between C. kutscheri and its alleged avirulent variant isolated from mice at the Rockefeller University. However, both capillary and double diffusion precipitin reactions showed the alleged variant to be a streptococcus of group N, indistinguishable from that previously isolated from Rockefeller University mice.


Comparison of the results of some serological tests for bovine brucellosis.

A total of 1887 bovine sera positive to the Rose Bengal plate test were subjected to other serological tests for bovine brucellosis: the complement fixation test using warm fixation (CFTW),the serum agglutination test (SAT) and the radioimmunoassay (RIA). The SAT was generally much less sensitive than the CFTW. Many sera, however, gave positive reactions in the SAT but no reaction in the CFTW or the RIA. These SAT reactions were attributed to IgM antibody. Comparison between the results of the CFTW and the RIA led to the conclusion that 200 ng could be used as a minimum diagnostic reaction in the RIA.


The diagnostic efficiency of some serological tests for bovine brucellosis.

Results obtained from 1887 sera using three serological tests for bovine brucellosis were compared with a serological classification of sera described as the 'probable infection status'. Sera showing apparent false positive and apparent false negative reactions were identified, and were subjected to supplementary testing as appropriate. The serum agglutination test (SAT) gave 35% apparent false negative reactions and 5% apparent false positives. The complement fixation test (CFT) gave 12% apparent false negative reactions using warm fixation (CFTW) and at least 5% using cold fixation (CFTC). The routine diagnostic system used in Victoria, in which the CFTW is supplemented by the CFTC and the SAT, gave 9% apparent false negative reactions and 2% apparent false positive reactions. The radioimmunoassay gave 1% or 6% apparent false negative reactions, depending on the minimum diagnostic value used. Atypical reactions in the CFT sometimes caused difficulties in diagnosis.


Determination of the position of electroimmune precipitates of antigen--antibody systems on their respective quantitative precipitation curves.

Using corresponding monospecific antisera from the rabbit, the precipitation curves for albumin, alpha-1-antitrypsin, haptoglobin 1-1 and fibrinogen were produced. In parallel, four different dilutions of these antigens were examined by line immmunoelectrophoresis, employing the same antisera. The distance of the resulting line immune precipitates from the start served to calculate the amount of antigen-antiserum reacting with each other. After converting these values to the amount of antiserum used for producing the precipitation curves, the 'line antigen/antibody ratios' were drawn into the appropriate precipitation curves. All electroimmune precipitates (in this case, the 'line immune precipitates') were found to be located on the side of antigen excess of their corresponding precipitation curve.


A solid phase radiommunoassay on hydrophobic membrane filters: detection of antibodies to gonococcal surface antigens.

A solid phase radioimmunoassay (SPRIA) has been developed for detection of IgG antibodies to gonococcal outer membrane components. Gonococcal antigens were immobilized on a solid support by covalent coupling to CNBr-activated Sepharose in the presence of the detergent Triton X-100. Binding of specific antibody to the Sepharose-antigen complex was detected using radiolabelled Protein A as the antiglobulin. Protein A was labelled by radioacetylation with tritiated acetic anhydride, yielding a product of high specific activity and high stability. No detectable loss of activity was observed over a ten month period. The entire assay was performed on Mitex teflon hydrophobic membrane filters which held the Sepharose beads and aqueous supernatant as a discrete drop of liquid. The supernatants and incubation media were easily and rapidly removed from the beads by suction on a specially designed manifold system. This procedure removed the need for repeated and time-consuming centrifugations. Titres were obtained graphically from double log plots of cpm bound versus antiserum dilution by extrapolation of the straight line to a point corresponding to twice the control level of radioactivity binding. The assay proved to be a very reliable and simple procedure for the detection of IgG antibodies to gonococcal surface antigens.


Rapid preparation of peroxidase: anti-peroxidase complexes for immunocytochemical use.

Soluble immune complexes of horseradish peroxidase and antibody to peroxidase (PAP) have been widely used in the 'unlabelled antibody' method for the immunocytochemical detection of cellular antigens. This paper describes a simple and rapid method for preparation of these complexes by column chromatography of a mixture of the enzyme and the IgG fraction of antiperoxidase antiserum on Sephacryl S-200. The material eluting in the void column consists of stable soluble PAP complexes, with a molar peroxidase: antiperoxidase ratio of 0.8 and a molecular weight of approximately 400,000. When tested immunocytochemically this material gives identical results to those obtained with conventionally prepared PAP.


Laurell crossed immunoelectrophoresis and affinity chromatography for the purification of a parasite antigen.

Laurell crossed immunoelectrophoresis (two-dimensional electroimmunodiffusion) was used to prepare minute amounts of purified parasite antigens complexed with their precipitating antibodies obtained from rabbits. These complexes, emuslified in Freund's complete adjuvant, were then used to prime rabbits for selective production of precipitins to the complexed antigens when the animals were later boosted with whole parasite extract. The IgG antibody from the monospecific antiserum recovered was then utilized in affinity chromatography to isolate from the crude parasite antigen large amounts of specific antigen in one step. Thus the combination of preparatory crossed immunoelectrophoresis for immunization using complexed antigen and affinity chromatography with monospecific antibody offers a powerful procedure for the rapid isolation of specific antigens.


Anogenital infection with Neisseria meningitidis in homosexual men.

Among monosexual men anal infection with Neisseria meningitidis was more prevalent (15 of 731 men) than expected and significantly more prevalent than urethral infection with N. meningitidis (three of 669 men, P less than 0.01). Anal infection was also significantly more prevalent among homosexual men than among heterosexual women (two of 1,197 women, P less than 0.001). These differences in rates of prevalence may be best explained by a preference of meningococci for anal mucosa and by the common homosexual practice of oral-anal sexual contact. Serogrouping of the 17 anal and three urethral isolates revealed a broad representation of serogroups often found in meningococcal pharyngeal carriage in the community. Of 14 patients who returned for a test-of-cure culture within seven days of treatment with an antibiotic regimen recommended for anogenital gonococcal infection, each was culture-negative for N. meningitidis. Minor and symptoms in three men and profuse urethral discharges in two men resolved with treatment.


Comparative toxicity of netilmicin and gentamicin in squirrel monkeys (Saimiri sciureus).

Netilmicin was found to be less toxic than gentamicin when administered at comparable dosage levels to squirrel monkeys (Saimiri sciureus). This finding is based upon data obtained from the following determinations: length of survival period; change in body weight; observation of general change in behavior after daily injection; ataxia, as measured by the squirrel monkey platform-runway test; acoustic reflex threshold; levels of blood urea nitrogen and serum creatinine (and pathology of the kidney); and microbiological antibiotic assay.


Similar content of phospholipids and gangliosides in normal and homozygous familial hypercholesterolemia fibroblasts.

The cellular content of total and individual phospholipids and gangliosides was measured in fibroblasts cultured from four normal subjects, three patients with lysosomal lipid storage diseases, and two subjects with homozygous familial hypercholesterolemia. Measurements were made on cells grown in medium containing fetal calf serum under conditions in which normal cells derive cholesterol for cell growth from low density lipoprotein present in the fetal calf serum, whereas familial hypercholesterolemia homozygote cells, which lack cell surface low density lipoprotein receptors, derive cholesterol from endogenous synthesis. No difference was observed in the cellular content of total or individual phospholipids and gangliosides in the normal and familial hypercholesterolemia homozygote cells. In contrast, cells from a patient with Niemann-Pick disease and a patient with Sandhoff disease showed elevations in the content of sphingomyelin and complex gangliosides, respectively.


Experiences with intra-oral partial resection and simultaneous reconstruction in cases of mandibular osteomyelitis.

A review of the surgical treatment of 17 cases of mandibular osteomyelitis is presented in which, following certain special indications, resection and simultaneous reconstruction of parts of the mandible were performed. This treatment was successful in 15 of the 17 patients considered. In two cases, the necrotic graft had to be removed. In one of them, the immediate reconstruction was successfully repeated. The indications for immediate reconstruction are given and the principles of the procedure described.


[The development of urogenital organs after lateral mesoblast heterotopic graft in the toad (Bufo bufo) neurula. II. Simultaneous inversion of anteroposterior and dorsoventral axis of the lateral plate].

Simultaneous inversion of the anteroposterior and dorsoventral axes of the lateral mesoblast in the early toad neurula leads to the total agenesis of the urogenital organs. The experimental results show that the lateral mesoblast is unable to undergo self-differentiation, and that three factors at least are required for the formation of the urogenital blastemata. The mesoblast must be competent: only the posterior (dorsal, but also ventral) part of the lateral mesoderm is endowed with this competence. It must receive two stimulating influences, from the cordomesoblast on the one hand, and from the dorsocaudal endoblast on the other hand.


Developmental analysis of the tumorous head mutation in Drosophila melanogaster.

The extent and type of adult transformations in the tumorous head (tuh) mutation of Drosophila melanogaster were studied. The observations indicate homeotic transformations, duplications and deficiencies of eye antennal disc derivatives. Contrary to previous observations there is no transformation of eye to abdomen and the only homeotic transformations identifiable are antenna to leg and rostralhaut to genitalia. Embryonic and post-embryonic lethality was also examined. Specific anterior abnormalities were found in embryos leading to early death. The amount of embryonic lethality was not affected by increased temperature during oogenesis. When analysing the adult phenotype, however, the whole period of oogenesis was sensitive to pulses of increased temperature; the pulses however did not have to be restricted to any particular stage of oogenesis to be effective in increasing tuh penetrance. The increase in the penetrance of the adult transformations is also exhibited when eggs are moved from 25 degrees C to 29 degrees C from the 8th to the 12th hour of embryonic development. Experiments indicate that the tuh-3 gene is active before the 8th hour of embryogenesis.


Neutralization of meningococcal endotoxin by antibody to core glycolipid.

Antibodies to Escherichia coli J5, a uridine 5'-diphosphate-galactose epimerase-less mutant of E. coli 0111, neutralized meningococcal endotoxemia from all three major capsular serogroups. We chose the dermal necrosis of the local Shwartzman phenomenon and the renal cortical necrosis of the general Shwartzman phenomenon as assays because these are the hallmarks of meningococcemia, and because meningococcal lipopolysaccharide (LPS) is a uniquely potent cause of dermal purpura and necrosis. Meningococcal antisera raised against LPS from MGC A, B, and C also provided good protection against endotoxemia from the homologous capsular groups, but it was inconsistent against the heterologous serogroups. The superiority of J5 antibodies (purified IgG as well as antiserum) is probably due to the fact that J5 LPS contains only the endotoxin core. Consequently, immunization with this mutant stimulates production of antibodies to core LPS without interference by the "0" antigenic determinants of the side chains. These observations indicate that the endotoxin core is the toxic moiety of meningococcal LPS, that the core LPS of meningococcus (MGC) is immunologically similar to enteric LPS, and that the antigenically variable "0" side chains of MGC LPS interfere with antibody production against the common core. They also suggest that antibodies prepared against this E. coli mutant could interrupt the devastating course of meningococcal endotoxemia in man, regardless of the capsular serogroup of the infecting strain.


In vitro analysis of allogeneic lymphocyte interaction. II. I-region control of the activity of a B-cell-derived H-2-restricted allogeneic effect factor and its receptor during B-cell activation.

A genetically restricted allogeneic effect factor (AEF) derived from a mixed lymphocyte culture reaction between Ia-negative activated responder cells and irradiated T-cell-depleted stimulator cells was characterized. Restricted AEF is a B-cell-derived soluble helper factor which consists in part of Ia antigens controlled by the I-A subregion of the stimulator haplotype; additional control by the I-B, I-E, and I-C subregions, although unlikely, could not be excluded. This factor helps B cells of only its own haplotype or of haplotypes which carry an I-A and/or I-B subregion identity. Unprimed as well as hapten-primed Ia-positive B cells express a receptor for restricted AEF. The results indicate that the B-cell receptor for AEF is determined by the I-A subregion. Both restricted AEF and its receptor may therefore be products of the same I-region gene(s). The data are compatible with the hypothesis that the AEF Ia antigens serve as a second signal required for B-cell activation to IgG antibody production.


Immunosuppressive factors from lymphoid cells of nonresponder mice primed with L-glutamic acid60-L-alanine30-L-tyrosine10. IV. Lack of strain restrictions among allogeneic, nonresponder donors and recipients.

The synthetic terpolymer of L-glutamic acid60-L-alanine30-L-tyrosine10 (GAT) fails to stimulate development of GAT-specific antibody responses in nonresponder mice but stimulates development of GAT-specific suppressor T cells that inhibit the development of normal anti-GAT plaque-forming cell responses to GAT complexed to methylated bovine serum albumin (MBSA). Extracts from lymphoid cells of GAT-primed but not control, nonresponder (DBA/1) mice contain a T-cell factor (GAT-TsF) that also specifically suppresses responses to GAT-MBSA by normal syngeneic spleen cells. The experiments reported in this communication demonstrate that: (a) extracts from all GAT-primed nonresponder mice tested contain GAT-TsF; (b) non-H-2 genes do not restrict the production of GAT-TsF; (c) all nonresponder strains of mice regardless of their non-H-2 genes are suppressed by GAT-TsF from all other strains bearing the nonresponder H-2p,q,s haplotypes; (d) suppression of GAT-MBSA responses by both syngeneic and allogeneic nonresponder spleen cells is mediated by a molecule encoded by the H-2 gene complex; and (e) both syngeneic and allogeneic nonresponder mice are suppressed by purified GAT-TsF that lacks immunoreactive GAT.


Isolated hapten-binding receptors of sensitized lymphocytes. III. Evidence for idiotypic restriction of T-cell receptors.

The primary antibody response of C57BL/6 mice to the 4-hydroxy-3-nitrophenylacetyl (NP) hapten is restricted to antibody molecules expressing the NPb idiotype. This idiotype is a genetic marker for V genes in the heavy chain linkage group. In the secondary response, the frequency of NPb idiotype-positive molecules within the antibody population drops to very low values. Accordingly, isolated NP binding receptors from NP-sensitized B lymphocytes are largely devoid of this idiotype. In contrast, the NPb idiotype is expressed on the majority of the receptor fractions which we consider T-cell derived. This finding suggests that the antigen receptors of T lymphocytes may be restricted to the expression of major (germ-line encoded?) heavy chain idiotypes.


Lung tumor-associated derepressed alloantigen coded for by the K region of the H-2 major histocompatibility complex.

Transplacental induction of lung tumors in C3HfeB/HeN (C3Hf) strain mice can be readily achieved with the carcinogen 1-ethyl-1-nitrosourea. Several of these tumors express, as a tumor-associated transplantation antigen (TATA), a normal tissue alloantigen present in strain A and C3H/HeN (C3H) mice. In the present study it was shown that the tumor-associated alloantigen on the C3Hf-derived lung tumor 85 was present in all mice of H-2(a) and H-2(k) haplotypes tested and in CBA (532) strain mice (H-2(ka) haplotype). Studies using congenic-resistant and recombinant strains of mice indicated that the genetic locus controlling the expression of this antigen was either within or to the left of the H-2K region of the major histocompatibility complex (MHC). Thus the antigen was expressed in B10.A (4R) mice (kkbbbb MHC haplotype) but not in B10 (bbbbbb) or B10.AQR mice (qkkddd). The antigen was expressed in all tissues tested of C3H and A strain mice. It was not detected on any tissue tested including embryo tissue of C3Hf mice or mice of MHC haplotype other than H-2(k) or H-2(a). Because C3Hf strain mice were originally derived from C3H strain mice (H-2(k)), the MHC haplotype of C3Hf mice has been provisionally designated H-2(kb). The finding of a tumor-associated change in the expression of a H-2K region-coded antigen is consistent with the concept that MHC-coded antigens may act as targets for immunological surveillance of tumors.


Genetic studies in NZB mice. I. Spontaneous autoantibody production.

The appearance of naturally occurring thymocytotoxic autoantibodies (NTA) and spontaneously produced antibodies to single-stranded DNA (ssDNA) was studied in NZB, and DBA/2 mice and their F1 and backcross progeny. NTA production was markedly decreased in males; however, castrated males produced quantities of NTA similar to those of females. Because the amount of NTA was influenced by sex hormones, it was necessary to gonadectomize all progeny to determine the mode of inheritance. Such studies suggested that NTA production was determined by a single locus with a gene dosage (codominant) mode of expression. The spontaneous production of antibodies to ssDNA appeared to be inherited as a single dominant genetic trait. The quantity of anti-ssDNA was also found to be under additional regulation; either a gene dosage effect or more likely a regulatory gene. The genes controlling the presence and quantity of ssDNA antibodies were not linked to the gene controlling the appearance of NTA.


Oligoclonal immunoglobulins, light chain ratios and free light chains in cerebrospinal fluid and serum from patients affected with various neurological diseases.

Several immunological parameters, of which the most important are the kappa-lambda ratios, the presence of free light chains and the double ring formation for kappa-chains in single radial immunodiffusion, were investigated in the cerebrospinal fluid and serum of patients affected with different neurological diseases. Parallels were run either with multiple sclerosis or subacute sclerosing panencephalitis. There seems to be a correlation between the frequency of the presence of free light chains and the degree of severity of the immunological process.


Light-induced voltage noise in the photoreceptor of Drosophila melanogaster.

The Drosophila photoreceptor potential is thought to be composed of discrete unit potentials called bumps. The steady-state receptor potential and the accompanying voltage fluctuations were recorded intracellularly under steady illumination. The occurrence rate, effective amplitude, and duration of the bumps were deduced by assuming a shot noise model. Over a wide range of light intensity, the duration of bumps remained essentially constant (25-30 ms). Below the saturation intensity for the receptor potential, the bump rate was roughly proportional to the intensity, and the adjustment of bumps to smaller size at higher intensity was mainly responsible for the nonlinear behavior of the receptor potential. The reduction in size of bumps at increasing light intensity was found to be due mainly to the diminishing magnitude of the bump current, and not to some other secondary effects. The bump rate saturated at about 3 x 105-106 events/s.


The effect of specific antiserum on the resistance of Neisseria gonorrhoeae to intracellular killing by phagocytes of human blood.

The high natural resistance of gonococci showing a characteristic 'double highlight' (DH) colonial morphology (Penn, Veale & Smith, 1977b) to intracellular killing by human phagocytes was markedly reduced by addition of rabbit antiserum to the phagocytosis medium or by preincubation of organisms with antiserum. Antisera raised to three different DH gonococcal strains showed a complex pattern of specificity in phagocytosis tests with the homologous organisms and three other DH strains. The effect of antiserum could be neutralized by adsorption with intact organisms or with extracts, prepared ultrasonically, of the homologous strain. Antiserum also promoted the intracellular killing of a strain which had a 'single highlight' colonial morphology (Penn et al., 1977b) and a low natural resistance to phagocytic killing, but adsorption with this strain neutralized the antiserum less consistently than the DH strain. The neutralization of antiserum-mediated promotion of intracellular killing by extracts of organisms naturally resistant to such killing may provide an assay for the aggressins responsible for this resistance.


Carboxymethylcellulase produced by facultative bacteria from the hind-gut of the termite Reticulitermes hesperus.

Bacillus cereus RW1 and Serratia marcescens RW3, isolated from the hind-gut of the termite Reticulitermes hesperus, both grew well on mesquite wood and produced moderate amounts of carboxymethylcellulase. Carboxymethylcellulose (CMC) gels were depolymerized rapidly by B. cereus RW1 and slowly by S. marcescens RW3. The depolymerization of CMC was pH and temperature sensitive. Depolymerization of gels by growing cultures of B. cereus RW1 and the action of cell-free extracts of B. cereus RW1 on CMC sols were optimum at pH 6.0 and 5.5, respectively. Glucose and cellobiose increased the rate of CMC gel depolymerization. Enzyme synthesis rather than growth was stimulated by the addition of glucose to a culture of RW1 growing on a non-cellulosic substrate. Bacillus cereus RW1 produced both cell-free and cell-bound carboxymethylcellulase.


Some factors controlling the attachment of the rumen holotrich protozoa Isotricha intestinalis and I. prostoma to plant particles in vitro.

The rumen holotrich protozoa Isotricha intestinalis and I. prostoma showed chemotaxis to sucrose, glucose and fructose. They attached themselves, by means of an organelle on the anterior cell surface, to particulate sources of these carbohydrates provided soluble protein was present in the medium. The concentration of protein eliciting attachment varied with the species and the state of nutrition of the cell, but was between 20 and 150 microgram ml-1. Attachment occurred only if the concentration of carbohydrate, at its source, exceeded the chemotaxis threshold concentration (50 micrometer for sucrose) and if it was less than 1 mM. At concentrations exceeding 1 mM, indiscriminate attachment to gas-liquid and solid-liquid interfaces occurred, provided the protein concentration was high enough to elicit attachment. In the rumen, soluble carbohydrates diffusing from food particles may attract the protozoa which attach themselves to the particles in the presence of soluble plant protein at less than 20 microgram ml-1; these conditions exist in the host animal soon after feeding when fed infrequently. The attachment mechanism may confer an ecological advantage on the Isotricha spp. over other rumen organisms dependent on soluble carbohydrates as energy and carbon sources.


Transformation of group F streptococci by plasmid DNA.

When the Challis strain of Streptococcus sanguis was transformed by the 17 megadalton beta plasmid from Streptococcus faecalis strain DS5, the plasmid underwent a 1.5 megadalton deletion (LeBlanc & Hassell, 1976). Furthermore, the covalently closed circular (CCC) plasmid DNA isolated from Challis transformants was rapidly converted to a linear form which did not possess any detectable transforming activity. To obtain stable CCC plasmid DNA a competent culture of a Lancefield group F streptococcus, strain DL8 (ATCC 12393), was used as a recipient of beta plasmid DNA. The plasmid DNA isolated from group F transformants exhibited the same configuration and size characteristics as the DS5 beta plasmid, and the CCC configuration was stable upon storage. CCC plasmid DNA from a group F transformant was biologically active and, when added to competent cultures of strain DL8, transformed them at frequencies about 100-fold greater than did beta plasmid DNA from DS5. This suggests the existence of a restriction--modification system in strain DL8.


Demonstration by light and electron microscopy of capsules on gonococci recently grown in vivo.

A study by light microscopy, using Leishman's stain alone or Leishman's stain followed by nigrosin, showed the presence of capsules on gonococci of two strains subcultured from subcutaneous chambers in guinea pigs. With the Alcian blue method of preparation for electron microscopy, gonococci of both strains recently grown in vivo showed densely stained capsules on some cells, while others in the same preparation showed only irregular masses of dense material on their surfaces with strands connecting adjacent bacteria. Treatment with antiserum, complement and conglutinin revealed irregular masses and strands of extracellular material with fixatives that did not contain Alcian blue.


Interferon enhances the fragility of lysosomes in L-929 mouse fibroblasts.

Infection of interferon-treated L-929 mouse fibroblasts with vaccinia WR virus is followed by severe cytolysis within 3 to 4 h. It is shown that this cytolysis cannot be caused by enzymes released from lysosomes into the cytosol. However, there is evidence that homologous interferon has a noxious effect on lysosomes. This phenomenon appears to be another aspect of the anticellular functions of interferon.


Neuroaxonal dystrophy (Seitelberger's disease) with late onset, protracted course and myoclonic epilepsy.

We present the pathologic findings, including electron microscopy, in one of two affected borthers with severe progressive myoclonus epilepsy, beginning in our patient at the age of 10 and leading to death at age 23. At autopsy there was widespread and marked neuroaxonal dystrophy, severe cerebellar atrophy, and tract degenerations in the gracilis columns and the lateral corticospinal tracts in the spinal cord. There was no increased pigmentation in the globus pallidus or reticular zone of the substantia nigra, on gross or microscopic examination. We regard this case as an example of a juvenile form of neuroaxonal dystrophy (Seitelberger's disease). The absence of pallido-nigral hyperpigmentation distinguishes this disease from Hallervorden-Spatz disease, which we regard as a separate disease entity.


Variability in somatosensory cortical neuron discharge: effects on capacity to signal different stimulus conditions using a mean rate code.

1. The present study is based on the demonstration (8, 9) that the relationship between mean interval (MI) and standard deviation (SD) for stimulus-driven activity recorded from SI neurons is well fitted by the linear equation SD = a X MI + b and on the observations that the values of the slope (a) and y intercept (b) parameters of this relationship are independent of stimulus conditions and may vary widely from one neuron to the next (8). 2. A criterion for the discriminability of two different mean firing rates requiring that the mean intervals of their respective interspike interval (ISI) distributions be separated by a fixed interval (expressed in SD units) is developed and, on the basis of this criterion, a graphical display of the capacity of a neuron with a known SD-MI relationship to reflect a change in stimulus conditions with a change in mean firing rate is derived. Using this graphical approach, it is shown that the parameters of the SD-MI relationship for a single neuron determine a range of firing frequencies, within which that neuron exhibits the greatest capacity to signal differences in stimulus conditions using a frequency code. 3. The discrimination criterion is modified to incorporate the changes in the symmetry of the ISI distribution observed to accompany changes in mean firing rate. It is shown that, although the observed symmetry changes do influence the capacity of a cortical neuron to signal a change in stimulus conditions with a change in mean firing rate, they do not alter the range of firing rates (determined by the parameters of the SD-MI relationship) within which the capacity for discrimination is maximal. 4. The maximal number of firing levels that can be distinguished by a somatosensory cortical neuron (using the same discrimination criterion described above) discharging within a specified range of mean frequencies also is demonstrated to depend on the parameters of the linear equation which relates SD to MI. 5. Two approaches based on the t test for differences between two means are developed in an attempt to ascertain the minimum separation of the mean intervals of the ISI distributions necessary for two different mean firing rates to be discriminated with 80% certainty.


Comparison of responses of warm and nociceptive C-fiber afferents in monkey with human judgments of thermal pain.

1. Radiant-heat stimuli of different intensities were delivered every 28 s to the thenar eminence of the hand of human subjects and to the receptive fields (RFs) of 58 "mechanothermal nociceptive" and 16 "warm" C-fibers, most of which innervated the glabrous skin of the monkey hand. A CO2 infrared laser under control via a radiometer provided a step increase in skin temperature to a level maintained within +/- 0.1 degrees C over a 7.5-mm-diameter spot. 2. Human subjects categorized the magnitude of warmth and pain sensations evoked by stimuli that ranged in temperature from 40 to 50 degrees C. The scale of subjective thermal intensity constructed from these category estimates showed a monotonically increasing relation between stimulus temperature and the magnitude of warmth and pain sensations. 3. The mechanothermal fibers had a mean RF size of 18.9 +/- 3.2 mm2 (SE), a mean conduction velocity of 0.8 +/- 0.1 m/s, mean thresholds of 43.6 +/- 0.6 degrees C for radiant heat and 5.95 +/- 0.59 bars for mechanical stimulation, and no spontaneous activity. In contrast, warm fibers had punctate RFs, a mean conduction velocity of 1.1 +/- 0.1 m/s, heat thresholds of less than 1 degrees C above skin temperature, no response to mechanical stimulation, and a resting level of activity in warm skin that was suppressed by cooling. 4. The cumulative number of impulses evoked during each stimulation in the nociceptive afferents increased monotonically as a function of stimulus temperature over the range described by humans as increasingly painful (45-50 degrees C). Nociceptive fibers showed little or no response to stimulus temperatures less than 45 degrees C that elicited in humans sensations primarily of warmth but not pain. In contrast, the cumulative impulse count during stimulation of each warm fiber increased monotonically with stimulus temperature over the range of 39-43 degrees C. However, for stimuli of 41-49 degrees C the cumulative impulse count in warm fibers was nonmonotonic with stimulus temperature. Warm-fiber response to stimuli of 45 degrees C or greater usually consisted of a short burst of impulses followed by cessation of activity. 5. The subjective magnitude of warmth and pain sensations in humans and the cumulative impulse count evoked by each stimulus in warm and nociceptive afferents varied inversely with the number, delivery rate, and intensity of preceding stimulations. 6. The results of these experiments suggest the following: a) that activity in the mechanothermal nociceptive C-fibers signals the occurrence of pain evoked by radiant heat, and that the frequency of discharge in these fibers may encode the intensity of painful stimulation; b) that activity in warm fibers may encode the intensity of warmth at lower stimulus temperatures, but is unlikely to provide a peripheral mechanism for encoding the intensity of painful stimulation at higher stimulus temperatures.


Oral lichen planus: the evidence regarding potential malignant transformation.

A critical review of the literature was undertaken to determine if there is valid data to support the contention that oral lichen planus represents a disease with significant potential for malignant degeneration. Although there are reports alleging such a relationship, there is insufficient documented evidence to state with any degree of confidence that oral lichen planus, in itself, represents a premalignant state.


Calcifying odontogenic cyst with ameloblastic fibro-odontome: one lesion or two?

The calcifying odontogenic cyst is unusual in that it is frequently found in conjunction with the histologic features of a variety of other odontogenic conditions. Two cases are reported, one of which contained areas histologically similar to the ameloblastic fibro-odontome and also showed condensations of cells in the stroma beneath epithelial strands proliferating from the cyst lining. In both cases the "ghost cells" stained strongly for disulphide groups but only occasional areas were positive for sulphydryl groups. No amyloid or "amyloid-like" material was detected. As no part of the current name is specific to this lesion it is suggested that the nomenclature should be changed--perhaps to "ghost cell dyst".


The prevalence of consolidated salivary deposits in the small ducts of human submandibular glands.

Deposits of apparently solid material were observed in the small salivary ducts in a series of non-diseased submandibular glands obtained from necropsies evenly divided by sex and adult age. The deposits were of granular or laminated structure. They were of mixed staining, the majority being predominantly eosinophilic. A small number of deposits were essentially wholly hematoxylinophilic and some of these were probably calcified. The prevalence of deposits, expressed as the number per unit sectional area, increased steadily with increasing age but was unrelated to sex. An apparently close correlation between intraductal salivary deposits and foci of obstructive adenitis in the same series of glands was shown to be mainly due to the common influence of age. The deposits probably form by precipitation of salivary glycoprotein, possibly because of parenchymal age changes. They may be related to early salivary lithogenesis but the statistical evidence of this study suggests that they are unlikely to be a major factor in the etiology of focal obstructive adenitis.


Lingual carcinogenesis in an inbred strain of hamsters.

Epidermoid carcinoma of the lateral border of the tongue can be induced in a standard strain of hamsters, applying DMBA in acetone after traumatizing the area with a root canal broach. Employing the same technique in an inbred strain of hamsters resulted in the more rapid development of carcinomas. The inbred strain should be a useful model for experimental carcinogenesis of tongue.


The influence of extracellular calcium binding on the calcium efflux from squid axons.

1. The Ca efflux from unpoisoned squid axons seems to consist of three components: Cao-dependent Ca efflux and a 'residual' flux that persists in the nominal absence of external Ca and Na and is little affected by the further removal of external Mg. 2. Evidence is presented to show that much of the apparent dependence on Cao of the Ca efflux from unpoisoned axons probably does not reflect a membrane process but results instead from the existence of a Ca-binding matrix external to the plasma membrane. Removal of external Ca produces a fall in efflux which is not maintained but returns to its original level over 20-60 min. Readmission of Ca produces only a transient increase in Ca efflux. Addition of EGTA to nominally Ca-free media also produces only a transient rise in Ca efflux. 3. Direct measurement of Ca binding to the surface of highly cleaned axons reveals appreciable binding over a wide range of Ca concentrations. A high affinity component of superficial binding can be recognized which has a capacity of about 60 p-mole/cm2 axon membrane and is half-maximal about 0.3 micrometer-Ca in Na-ASW. This component of binding is unaltered in cyanide-poisoned axons and in media in which Na is replaced isosmotically by Tris; but is reduced in the presence of 1 mM-La or after brief exposure of the axon to pronase. There is also a component of large capacity and lower affinity which was not saturated by 100 mM-Cao. 4. After brief pronase treatment the sensitivity of the Ca efflux to external Ca is markedly reduced although the Na-dependent Ca efflux persists apparently unaltered. 5. Addition of La produces a transient increase in Ca efflux followed by a maintained fall. 300 micrometer-La largely inhibits the component of the Ca efflux that persists in the nominal absence of external Na and Ca. Higher concentrations of La also inhibit Nao-dependent Ca efflux. 6. The Cao-dependent Ca efflux and Nao-dependent Ca efflux seen in poisoned axons persist in the presence of EGTA or after pronase treatment, suggesting that both are genuine membrane processes. 7. We conclude that in unpoisoned axons 50-90% of the Ca efflux can continue in the absence of external Ca, Na and Mg and may reflect an uncoupled extrusion of Ca. Most of the remaining efflux from these axons is Nao-dependent although a small Cao-dependent component can be distinguished in the absence of Na. Poisoning results in the loss of uncoupled Ca efflux, the appearance of appreciable Cao-dependent Ca efflux and alteration in the kinetics of Nao-dependent Ca efflux.


Deficient influence of peripheral stimuli on precentral neurones in monkeys with dorsal column lesions.

1. Four male monkeys (M. fascicularis) were trained in a movement performance task which involved pulling a horizontal lever into a target zone and then collecting, from one of a variety of positions, a small food reward. The same animals were also trained to sit quietly and accept passive manipulation and natural stimulation of the arm and hand while remaining relaxed. 2. After complete bilateral section of the cuneate fasciculi or division of a major part of these dorsal column afferents at C1-C2 or at C5 level, the animals were still able to perform movement tasks normally. Disturbance of discrimination ability was revealed after vision was occluded it the animal was required to detect differences in texture with only a small cutaneous area in contact with the object (e.g. using only the tip of the index finger). Contactual-placing reactions could be performed in the absence of vision and the movements the animal made in these reactions were well controlled and appropriately directed. Minimal disturbance of contact placing was noticed if the surface touched was on the hand or fingers or if the reaction involved crossed placing. 3. An examination of the natural discharges of 342 percentral neurones revealed that the patterns of activity exhibited in relation to complex movements were indistinguishable from patterns recorded in normal monkeys carrying out similar tasks. 4. Discharges of ninety-one of 321 precentral neurones could be produced by appropriate natural stimuli delivered within the cell's afferent input zone at the periphery. The zone from which a given cell could be influenced was usually limited and its location could be on any part of the contralateral forelimb. However, all but nine of these responses were found in animals in which a small proportion of the cuneate fibres remained intact. In an animal with histologically proven complete section of the cuneate faciculi very few (nine of 171) precentral neurones were influenced by natural activation of peripheral receptors in the forelimb. The zones from which these few afferent inputs were found could all have been proximal to the level of the cuneate lesion. 5. The very small number of responding pre-central neurones found in an animal with complete section of the cuneate fasciculi made it likely that the dorsal columns provide the major pathway for effects from circumscribed peripheral receptors in the forelimb to influence precentral neurones. However, even in an animal with complete interruption of cuneate fibres, a proportion of post-central neurones could still be influenced by natural activation of peripheral receptors within restricted regions of the forelimb. Hence the 'sensory' cortex was still in receipt of afferent projections which could be revealted readily by the tests used. 6...


The topographic organization of rhesus monkey prestriate cortex.

1. The topographic organization of prestriate visual cortex in the rhesus monkey has been studied both anatomically, by determining the pattern of termination of fibres passing through the corpus callosum, and physiologically, in the same animals, by plotting receptive field positions for different recording sites. Results are displayed on two-dimensional, "unfolded" maps of the cortex in the dorsal half of the occipital lobe. 2. Transcallosal fibres terminate in a narrow strip of cortex along the boundary between striate and prestriate areas and in a separate, broader, zone occupying much of the anterior bank of the lunate sulcus, the annectant gyrus, and the parietooccipital sulcus. The detailed pattern of inputs is highly complicated but shows considerable similarities from one animal to the next. 3. Physiological recordings confirmed earlier reports that regions where transcallosal fibres terminate correspond to representations of the vertical meridian in the visual field. This relationship is most precise along the striate-prestriate boundary and along the boundary of area V3 farthest from V1; it is less precise within area V4, where the pattern of transcallosal inputs is more complex. 4. A distinct, topographically organized visual area, named V3A, was found in the region between areas V3 and V4 in the lunate and parieto-occipital sulci. Area V3A differs from V2 and V3 in that both superior and inferior visual quadrants are represented in a single region of the dorsal occipital lobe. 5. The contralateral visual field is represented in a suprisingly complex fashion in areas V3A and V4. Within each area there are multiple representations of some, but perhaps not all, parts of the visual hemifield. It is unclear whether V3A and V4 should be more appropriately considered as sets of distinct sub-areas, each representing only a portion of the hemifield, or as larger areas with complicated internal topographies. 6. Most cells in areas V2, V3 and V3A are orientation selective but not selective for stimulus colour or direction of movement. In contrast, area V4 contains a higher incidence of colour selective cells and a lower incidence of orientation selectivity. These results support the notion of a functional division of labour within the prestriate cortex.


The cortical projections of foveal striate cortex in the rhesus monkey.

1. The cortical projections of the foveal and extrafoveal parts of the striate cortex have been compared, using conventional degeneration techniques, as well as combinations of anatomical methods. While both foveal and extrafoveal striate cortex share a common pattern of projections (to areas V2, V3 and the visual area in the medial part of the posterior bank of the superior temporal sulcus), foveal striate cortex was found to have an additional projection (to part of the cortex of the fourth visual areas, V4). The latter projection includes the posterior lip of the inferior occipital sulcus which, on anatomical grounds, is regarded as the ventral extension of V4. 2. Anatomical studies using double tracers were employed to clarify the nature of the projections from the striate cortex and from V2 to V4. In one such experiment, tritiated proline was injected into extra-foveal striate cortex and a small lesion was made in that part of V2 receiving a direct projection from the region of the striate cortex into which the radioactive tracer was injected. Only degenerating fibres (due to the lesion), and no radioactive label, was found in V4. Such an experiment showed that, unlike foveal striate cortex, the projections from extrafoveal striate cortex to V4 are not direct, but through V2. 3. In another type of anatomical experiment using double tracers, the corpus callosum was sectioned and tritiated proline was injected into foveal striate cortex. Such an experiment allowed a more accurate determination of the extent of V4, as judged from its callosal connexions, to which foveal striate cortex projects. 4. Considering the projections of V1 to areas V2, V3 and the visual area in the medial part of the posterior bank of the superior temporal sulcus, and considering the differences in the projections of foveal and extrafoveal striate cortex, it is suggested that, among other functions, the striate cortex acts as a distribution centre for the information coming over the retino-geniculo-cortical pathways, parcelling this information out to different visual areas of the prestriate cortex for further analysis.


The third visual complex of rhesus monkey prestriate cortex.

1. Two independent but neighbouring visual areas, V3 and V3A, sharing a common cytoarchitectural plan, but in each one of which the visual fields are separately represented, have been studied anatomically, functionally, and in combined anatomico-physiological experiments. 2. The properties of single cells in the two areas are so similar, judged by the techniques used in this study, that it is often impossible to tell whether any one penetration was sampling from cells in V3 or V3A. This is especially so if the cells have receptive fields in the lower hemi-quadrants, since the vertical meridian of the lower visual fields is represented along the V3-V3A boundary and since a transition from V3 to V3A along this border is not accompanied by a shift in receptive field positions of cells. 3. Since the visual fields, including the vertical meridian, are separately represented in these two areas, and since regions of vertical meridian representation are callosally connected, a simple and certain method of specifying the boundary between V3 and V3A is to examine the degeneration following section of the callosal splenium. A heavy patch of degeneration then marks the V3-V3A boundary. Within this patch, however, is a sub-patch containing fewer callosal fibres, or none at all. The boundary between V3 and V3A was taken to be at this subpatch. 4. Since the horizontal meridian is represented at the V2-V3 boundary, and since V1 projects to both these areas, sending coarse fibres to V3 and fine fibres to V2, it was found that the boundary between V2 and V3 could be precisely drawn by making a lesion in the horizontal meridian representation in V1 and noting where, in the prestriate cortex, fine fibres give way to coarse ones, without an intervening gap. 5. Double tracer anatomical experiments, in which tritiated proline was injected into V1 of animals whose callosal splenium had been sectioned, showed that whereas V3 receives a direct input from V1, V3A does not. V3A, instead, was found to receive an input from V3. Double tracer anatomical experiments were undertaken to study a possible input from V2 to V3A. Although such experiments did not reveal a direct input from V2 to V3A, they were not entirely conclusive. 6. The vast majority of cells in V3 and V3A were binocularly driven, without obvious monocular preferences. Some cells, however, though responding to stimulation of the individual eyes, summated their responses to binocular stimulation. Others responded only when both eyes were simulataneously stimulated. In any oblique penetration, cells preferring binocular stimulation only occurred either singly or in groups. 7. In an oblique penetration, the shift from a cell responding to binocular stimulation only to one responding equally well to stimulation of either eye was not necessarily accompanied by a shift in orientational preferences, shifts in the former...


Uniformity and diversity of structure and function in rhesus monkey prestriate visual cortex.

1. Recordings were made from single neurones, or small clusters of cells, in five prestriate visual areas of rhesus monkey cortex. The cells were studied for their binocularity, as well as for their orientational, motion and colour preferences. In all, 1500 cells were studied, 250 cells for each of the areas V2, V3, V3A and the motion area of the posterior bank of the superior temporal sulcus, and 500 cells for V4. All the cells referred to in this study can be placed in one prestriate area or another unambiguously. 2. The great majority of cells in all areas were binocularly driven, without monocular preferences. Within each area, there were cells that either preferred binocular stimulation markedly, or were responsive to binocular stimulation only. The ocular interaction histograms for all areas are remarkably similar when tested at a fixed disparity. 3. Over 70% of the cells in areas V2, V3 and V3A were selective for orientation. The receptive fields of cells were larger in V3 and V3A than in V2. By contrast, less than 50% of the cells in V4 and the motion area of the superior temporal sulcus were orientation selective. 4. Directionally selective cells were found in all areas. But they were present in small numbers (less than 15%) in areas V2, V3, V3A and V4. By contrast, 90% of the cells in the motion area of the superior temporal sulcus were directionally selective. 5. 8% of the cells in V2 had opponent colour properties. Cells with such properties were not found in V3, V3A or in the motion area of the superior temporal sulcus. By contrast, 54% of the cells in the V4 complex had opponent colour properties. 6. It is argued that despite its uniformity in cytoarchitectural appearance and in ocular interaction patterns, there is a functional division of labour within the prestriate cortex. Evidence for this is seen not only in the different concentrations of functional cell types in distinct areas of the prestriate cortex, but also in the differential anatomical and callosal connexions of each area.


Liquid-sensitive laryngeal receptors in the developing sheep, cat and monkey.

1. Action potentials were recorded from single afferent units of the superior laryngeal nerves in neonatal and adult sheep, cats and monkeys when liquids were passed over the laryngeal mucosa. 2. Two types of mucosal receptors, sensitive to water but not to isotonic saline, were found in each species from birth. The most common type of unit responded after a short latency (less than 1 sec), discharged maximally in the first 1-3 sec and became inactive when the stimulus was withdrawn. The other type responded only after several seconds, the discharges gradually increasing in frequency and continuing after removal of the stimulus. 3. Reproducible responses were elicited by tactile stimulation of the laryngeal mucosa over the receptive field of each of the long-latency units. Fewer than 50% of the short-latency units were excited, the remainder responding only unreproducibly to firm pressure. 4. Short-latency, but not long-latency, units responded to milks, gastric contents, saliva and isotonic solutions of sugars. 5. The responses of long-latency units to water were often modified by, but rarely dependent on, reflexly evoked activity in laryngeal muscles. 6. The conduction velocities of afferent fibres of water sensitive units ranged from 22 to 49 m/sec, and differed little from those of water-insensitive laryngeal mechanoreceptors. 7. Histological examination of the laryngeal mucosa showed that taste buds were present in lambs from birth whereas they developed post-natally in kittens and monkeys. The evidence suggests that taste buds were not associated with water-sensitive units.


[Bone lesions in a case of heavy chain alpha disease (author's transl)].

Specific bone lesions are not usually found in heavy chain alpha disease we report a case in which images identical to those seen in Parker and Jackson's sarcoma (bone lymphoma) were found. The malignant lymphomatous nature of the lesion could not be confirmed as a bone biopsy was not made, but its regression under chemotherapy makes the diagnosis almost certain. Indirectly, arguments in favour of this hypothesis can be drawn from the common cellular origin of bone lymphomas and monoclonal gammopathies. Furthermore, it is logical to assume that heavy chain alpha disease, as with most other immuno-proliferative syndromes, can be associated with malignant lymphomatous changes in the skeleton.


Spiro[isobenzofuran-1(3H),4'-piperidines]. 3. Diuretic and antihypertensive properties of compounds containing a sulfur attached to nitrogen.

The synthesis and antihypertensive and diuretic activity of several N-sulfur derivatives of 3-phenylspiro[isobenzofuran-1(3H),4'-piperidine] are reported. Benzenesulfenamide 3 possessed marked, species-specific diuretic and antihypertensive activity in rats.


Vasopressin-like effects of a hallucinogenic drug--harmaline--on sodium and water transport.

To determine if harmala alkaloids affect transport systems other than (Na +K)-ATPase, effects of harmaline on Na and water fluxes were studied in amphibian skins. Net Na flux was evaluated from short-circuit current, and water flux monitored with automatic, volumetric methods. At 2 to 5 mM, harmaline consistently inhibited SCC and prevented the natriferic effects of oxytocin and norepinephrine. However, at 0.1 to 0.5 mM, harmaline produced an increase in SCC inhibitable with amiloride. The stimulatory effects of harmaline and oxytocin were either nonadditive or additive depending on whether the hallucinogen was present in the inner solution or in the outer solution bathing the skin, respectively. Water flow was not modified by harmaline on the outer medium. In contrast, addition of the drug to the inner medium elicited a conspicuous, sustained, vasopressin-like, hydrosmotic effect, comparable to and competive with those of vasopressin and norepinephrine. The ensemble of these results suggests that harmaline may affect three distinct transport systems: (i) the Na pump; (ii) the cyclic nucleotide system; (iii) the Na entry pathway at the outer membrane of the skin that is also activated by agents such as diphenylhydantoin, lanthanides and propranolol.


Isolation and metastatic properties of detachment variants of B16 melanoma cells.

Variant clones of B16 melanoma cells have been isolated that detached from plastic tissue culture dishes either more or less readily than the parent line upon treatment with EDTA or ethyleneglycol-bis(b-amino ethyl ether)N,N'-tetraacetic acid. Cells that detached more readily were spindlier in culture than parent cells, covered less surface area per cell, and formed fewer pulmonary tumors when injected iv into C57BL/6J mice. Cells that detached less readily were flatter in culture and formed more pulmonary tumors when injected iv than the parent cells. After detachment with EDTA, the cells reattached to culture dishes at the same rate.


Differences in purine metabolizing enzyme activities in human leukemia T-cell, B-cell and null cell lines.

Clear metabolic differences between T- and B-cells were demonstrated. Both adenosine deaminase (ADA) and nucleoside phosphorylase (NP) activities increased during logarithmic growth and then decreased in T-cells, but remained essentially constant during the growth cycle of B-cells. When these enzyme activities were examined in a number of T-cell, B-cell, and null cell lines, ADA activity was clearly higher in T-cells as compared to all others. With NP, the opposite appeared to be true, although the differences were much smaller and not statistically significant in all instances. No clear differences were found in the isoenzyme distributions of both enzymes in the various cell types.


Stimulation of malignant skin cells by antibody to normal skin cells of mice.

The ability of antibodies developed against normal skin cells to stimulate skin cells transformed by 7,12-dimethylbenz[a]anthracene (DMBA) was investigated. Primary cultures of normal skin, containing both fibroblasts and epithelial cells, were established from epidermis of the back skin of adult strain A/J mice. Malignant skin cells were obtained by treating a subculture of normal cells with DMBA. Transformation was demonstrated by increased growth rate, growth in soft agar, and production of tumors in strain A/J mice. Antisera developed in New Zealand White rabbits against the normal cells were cytotoxic to both normal and malignant cells in the presence of complement of 1:320 dilution. However, greater dilutions of the antisera (1:500-1:1,000) in the absence of complement produced growth enhancement of the malignant but not of the normal cells. The growth-enhancing properties were present in the gamma-globulin fraction of the antisera that contained IgG, IgM, and IgA antibodies. Immunofluorescence studies indicated that antibodies from the sera bound to the membranes of both normal and malignant cells. These data indicate that antibodies to normal cells are stimulatory to DMBA-transformed cells and confirm previous data obtained with spontaneously transformed cells.


Studies on endoparasites of the black bear (Ursus americanus) in the southeastern United States.

Examination of 53 black bears (Ursus americanus) from six states in the southeastern United States revealed at least 17 species of endoparasites, including Sarcocystis sp., Spirometra mansonoides (spargana), Macracanthorhynchus ingens, Ancylostoma caninum, Arthrocephalus lotoris, Baylisascaris transfuga, Capillaria aerophila, Capillaria putorii, Crenosoma sp., Cyathospirura sp., Dirofilaria immitis, Gnathostoma sp., Gongylonema pulchrum, microfilariae, Molineus barbatus, Physaloptera sp. and Strongyloides sp. Twelve of these represent new host records for black bear, and two are considered to be new species. Data are presented on prevalence, intensity and geographic distribution of each species. Pathologic effects were associated with infections of spargana of S. mansonoides and adults of C. aerophilia.


Parasites of the coyote (Canis latrans) in central Utah.

Seventeen coyotes, Canis latrans, from central Utah were surveyed for parasites. Five species of parasites not reported previously from coyotes in Utah were detected: Filaroides osleri, Physaloptera sp., Spirocerca sp., Ancylostoma caninum, and Cediopsylla simplex. In all, 11 genera of parasites were observed.


Caryospora cheloniae sp. n.: a coccidial pathogen of mariculture-reared green sea turtles (Chelonia mydas mydas).

Caryospora cheloniae sp. n. is described from mariculture-reared green sea turtles (Chelonia m. mydas). The sporulated oocyst has a thin, transparent, single-layered wall which often ruptures, leaving a naked sporulated sporocyst. Oocysts measured 33.8 to 40.1 micrometer by 11.0 to 14.6 micrometer (mean 37.4 by 12.8 micrometer). Greatest concentrations of developmental stages of C. cheloniae were found in the hindgut. Transverse binary fission was observed in dividing tissue stages. Pathologic alterations were most pronounced in the posterior third of the intestines (hindgut). The hindgut lumen was greatly dilated and filled with blood, oocysts and tissue debris. The hindgut wall was thinner than normal and the mucosal folds had sloughed into the intestinal lumen. Free blood escaped from the blood vessels of the tunica propria into the intestinal lumen. Epithelial hyperplasia was pronounced at the margins of denuded mucosal areas. Numerous inflammatory cells infiltrated the infected mucosal surface.


Rocky mountain spotted fever caused by blood transfusion.

Transfusion of 500 ml of blood, contributed by a donor three days before the onset of Rocky Mountain spotted fever and refrigerated for nine days, caused this disease in the recipient. The blood donor died of Rocky Mountain spotted fever after six days; rickettsia were identified in various tissues by immunofluorescence techniques. The recipient of the blood became mildly ill and recovered fully; specific antibiotic treatment was initiated on the fourth day of illness. Diagnosis of Rocky Mountain spotted fever was confirmed in the recipient by positive serologic reactions and isolation of Rickettsia rickettsii from blood after inoculation in animals and tissue culture.


Preliminary screening of amino acids excretion in the urine of newly born babies.

The paper attempts to characterize the qualitative as well as quantitative estimations of aminoacids in the urines of new born babies using two dimensional paper chromatography. The objective of this investigation was to know the extent of amino acid defects in these samples and to correlate such defects with the physical abnormalities in infants. Based on the overall results, it is inferred that phenylalanine excreted in the urine gave a positive response with PKU test and some particular amino acids are identified and estimated in the urine of new born babies to confirm the diagnosis of phenylketonuric patients.


Composition of gall stones-microchemical analysis.

The composition of gall stones removed surgically from 31 patients was determined by microchemical analysis. Twenty six had mixed infective, 2 cholesterol and 3 pigment stones. All the stones consisted of combination of various constituents in varying amount. Bilirubin was detected in the centre and peripheral layers of all, protein was found in the centre of 84.6% and cholesterol in the centre of 54% and the peripheral layers of all the gall stones. The findings in this study suggest that infection is the most likely cause of biliary lithogenesis.


[The effects of a new type of laser on fixed tissue of the angle of the anterior chamber in the monkey eye (author's transl)].

Segments of fixed tissue of the chamber angle of the monkey eye are irradiated with a neodymium (YAG-) q-spoiled laser at a pulse duration of 50 ns, a pulse energy of 200 mJ and an optic distance of 15 mm. Perforating injuries are observed between the anterior chamber and Schlemm's canal. When an acute angle of the laser beam relative to the cornea is chosen, the application point must be at the anterior part of the trabecular meshwork, close to the cornea, to open the canal of Schlemm. An impact further back toward the iris would create cyclodialysis.


[Diabetic cataract and flavonoids (first results) (author's transl)].

The possible effects of Quercetine, a potent inhibitor of aldose-reductase, on cataract formation and vascular permeability were investigated in streptozotocine-diabetic rats. Preliminary results after peroral administration of Quercetine did not allow to demonstrate a clear inhibitory effect on cataract formation.


Output value analysis of an alcoholism treatment program.

A form of cost--benefit analysis is used to measure the efficiency and effectiveness of an alcoholism treatment program in caring for patients grouped by year of admission, sex and level of impairment.


Age-dependent alpha-glycerophosphate dehydrogenase activity changes in mutant and wild type Drosophila melanogaster.

The age-related changes in the activity of the extramitochondrial alpha-glycerophosphate dehydrogenase (alpha-GPDH) were compared in two mutants of Drosophila melanogaster, a vestigial-winged and an alpha-glycerophosphate dehydrogenase deficient mutant with that of the wild type. The age-dependent patterns of activity change in both mutants were shown to be identical to that of the wild type. This is in spite of the lack of flight ability in both mutants, the reduced enzyme activity levels in the alpha-glycerophosphate mutant, and in the case of the vestigial flies, of reduced life-span. The results suggest that those mechanisms responsible for the observed aged-related activity changes in alpha-GPDH are intrinsically regulated, independent of functional flight, genetic alteration of specific activity, and life-span.


Patient outcomes in alternative long-term care settings.

The purpose of this study was to compare health status outcomes in three alternative long-term care settings in the Veterans Administration : 1) home care; 2) community-based nursing home care; and 3) hospital-based nursing home care. Patients were measured on a behavioral index of health status, at two points in time: when transferred from the acute care hospital to one of the three treatment programs (pretest and three months later (posttest). Since patients could not be randomly distributed to programs, two methods were employed to control for potential sample selection bias: the choice of a nonequivalent control group design, and multivariate analytic techniques. First, within each program type, patients were randomly selected from both a hospital that offered only that program as a long-term care alternative and from a hospital that provided all three treatment settings. Second, multiple regression analysis was used to control for pretest differences among patients. Patients placed in the home care program displayed the greatest mean improvement in functional health status, holding all other variables constant. This treatment effect was not uniform, however; patients showed differential rates of improvement across the three programs, based upon both initial health status and prognosis.


Assessing the impact of tonsillectomies.

This paper explores outcomes associated with the tonsillectomy operation using multiple control groups and a large claims-based data bank from the Canadian province of Manitoba. Given the difficulty of conducting large-scale clinical trials of common surgical procedures, the use of multiple methods for evaluating such interventions is both advocated and implemented in this study. When the data are restricted to respiratory diagnoses, the findings suggest that, on the average, tonsil surgery saves between one half and one and a half episodes of illness per patient over the two years after surgery. Such savings are much more pronounced among individuals having several tonsillitis episodes in the preoperative year. However, when all medical claims are considered, the estimated savings from the tonsillectomy operation are somewhat reduced. Individual variation in predisposition to "see the doctor" appears to account for such results; visits about conditions other than respiratory take up much of the "savings" produced by tonsil surgery. The findings are discussed in terms of the costs and benefits of the tonsillectomy operation, and future research needs are outlined.