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An infant with severe combined immune deficiency was delivered by Caesarean section and continuously maintained in an isolator in an effort to restrict microbial contact. However, during the past 5 years the child came in contact with at least 54 different microbial contaminants. His skin autoflora was similar to the reference group of healthy male adults in numbers of different species and the number of viable cells present per square centimeter of surface area. The subject's autoflora differed from the reference group in that significantly fewer anaerobic species were recovered from the patient's mouth and feces. The populations on the skin and in the upper respiratory tract were almost exclusively composed of staphylococci and micrococci, although several species that commonly inhabit these areas were infrequently isolated and failed to colonize. The fecal autoflora was dominated by staphylococci, and bacilli clostridia recovered in typical numbers. Enterobacter agglomerans, not commonly recovered from the reference group, was a frequent inhabitant of the mouth and feces of the child. The fact that this severe combined immune-deficient patient has remained disease free in the presence of this microbial population illustrates the noninvasive nature of the bacteria present, as well as the importance of unaffected components of the child's immune defense mechanism.

Because the diagnosis of squamous-cell carcinoma of the lung by routine cytologic screening of sputum is often inconclusive, our laboratory is studying the use of cytomorphologic profiles as a reliable diagnostic aid. This study reports the analysis of the profiles of 75 subjects, both cigarette-smoking volunteers and hospitalized patients suspect for lung cancer. Twenty-five of the subjects had been classified as having squamous metaplasia, 25 as having atypias and 25 as having squamous-cell carcinoma. Four slides were made for each subject, with 100 random fields viewed on each slide. The frequency of free alveolar macrophages, metaplastic squamous cells, epithelial atypical cells and malignant squamous cells were noted for each field. The results indicated that, although there were large differences between individual profiles within each diagnostic category, there were significant differences between the average profiles for each diagnostic category. Furthermore, although there were differences in cell frequencies from slide to slide and within slides, the differences were constant across diagnostic categories. The results are supportive of the progressive-atypia hypothesis for squamous-cell carcinoma of the lung and provide a baseline for comparison with subsequent individual profiles.

A sequence of oxidate facies sediments associated with a cupriferous massive sulphide deposit in the Solomon Islands is the product of precipitation at an exhalative fluid/seawater interface. A siliceous sinter bed within the sediments contains magnesioferrite spheroids having a distinctive framboid texture. Scanning electron micrographs of the spheroids show an internal structure of parallel rods composed of sub-spherical microcrysts. The formation of the magnesioferrite framboid texture is ascribed to the coagulation of magnetic iron hydroxide gel particles due to magnetic attraction but facilitated by the presence of a strong electrolyte. By analogy a simple mechanism to account for pyrite framboid formation is proposed. This mechanism requires primary iron sulphide particels to be attracted to one another because of the ferrimagnetic properties of a precursor FeS polymorph or alternatively by Van der Waals forces accentuated by the presence of charged ions in a strong electrolyte. Ordering of resultant microcrysts is mainly a close-packing effect which produces robust aggregates resistant to deformation during subsequent diagenesis.

The receptors for colony stimulating factor-1 (CSF-1), platelet derived growth factor and the c-kit protein tyrosine kinase (PTK) contain within their catalytic domains a stretch of 60-100 residues, largely unrelated in sequence, with no counterpart in other PTKs. Of the 64 amino acids within this kinase insert, 58 were deleted from the mouse CSF-1 receptor by oligonucleotide-directed mutagenesis. The mutant CSF-1 receptor was not markedly affected in its kinase activity, post-translational processing or its ability to induce autocrine transformation of NIH 3T3 mouse fibroblasts. Similarly, retention of kinase and transforming activities were observed following deletion of part or all of the kinase insert from the v-fms oncoprotein. The c- and v-fms kinase inserts were probed using monoclonal and polyclonal antibodies and were found to be highly antigenic. Two monoclonal antibodies raised to the v-fms cytoplasmic domain both recognized epitopes within the insert, and bound enzymatically active v-fms glycoproteins. These results indicate that the fms kinase insert is located on the surface of the protein and folds separately from the rest of the catalytic domain, but is not required for the biological activity of fms PTKs ectopically expressed in mouse fibroblasts. The insert may therefore play a specific function in cells such as monocytes and trophoblasts that normally express the CSF-1 receptor.

The atypia status index (ASI) is a categorization method of classifying digitized images of atypical bronchial epithelial cells in sputum. The ASI is defined as a linear composite of features linearly related to atypia stage. Over 200 features were examined for more than 3,000 cells that had been classified by atypia stage (squamous metaplasia, mild, moderate or severe atypia and malignant) and staining characteristic (orangeophilia and nonorangeophilia). We reduced the number of features by using a selection process to minimize redundancy. The feature weights were optimized via a least-squares procedure. The 14 features selected accounted for over 60% of the variation of atypia stage and produced ASI values that were within one atypia stage of the criterion classification for over 90% of the cells. The results are consistent with the hypothesis of a progressive pattern in bronchial epithelial atypia and indicate the feasibility of using image analysis for mass screening of premalignant atypias in sputum from subjects considered to be at high risk for lung cancer.

Equine steatitis is a rare condition which is usually reported in foals. A case of generalised steatitis in an adult pony mare is described and compared with steatitis in other species. It is concluded that the condition resembled that recorded in foals but that its aetiopathogenesis remains obscure.

Thymidylate biosynthesis was inhibited in a haploid heterothallic strain of Saccharomyces cerevisiae. When the treated cells were mixed with a haploid strain of the same mating-type, there was an increase in the recovery of diploid colonies. Genetic and biochemical analyses demonstrated that the diploid clones arose as a consequence of induced mating-type interconversion.

The typical microbial inhabitants of the oral and nasal cavities of Apollo astronauts were identified before space flight and generally found to be similar to those previously reported for healthy male adults. Additional analyses of samples collected immediately after return of the Apollo 13, 14, 15, and 16 crew members to earth were performed to evaluate the effects of space travel on the microbial bioburden of the upper respiratory tract. In-flight cross-contamination and buildup of pathogens such as Staphylococcus aureus were noted, although significant increases in nonpathogenic species were absent. Other proposed alterations, such as dysbacteriosis (flooding of the mouth with a single species) and simplification of the autoflora, did not occur. Generally, the incidence and quantitation of each species after flight was within the preflight range, although the number of viable Haemophilus cells recovered from the mouth decreased significantly after space flight. Except for those minor alterations listed above, the aerobic and anaerobic bacterial components of the upper respiratory autoflora of Apollo astronauts was found to be stable after space flight of up to 295 h.

Visual cell profiles were used to analyze the distribution of atypical bronchial cells in sputum specimens from cigarette-smoking volunteers, cigarette-smoking asbestos workers and cigarette-smoking uranium miners. The preliminary results of these sputum visual cell profile studies have demonstrated distinctive distributions of bronchial cell atypias in progressive patterns of squamous metaplasia, mild, moderate and severe atypias and carcinoma, similar to those the authors have previously reported using cell image analysis techniques to determine an atypia status index (ASI). The information gained from this study will be helpful in further validating this ASI and subsequently achieving the ultimate goal of employing cell image analysis for the rapid and precise identification of premalignant atypias in sputum.

Streptomyces levoris Kras was used is an experimental test micro-organism during the Apollo Soyuz Test Project to study alternating vegetative mycelial and spore ring periodicity during space flight. Four cultures were launched in each of the spacecrafts (Apollo and Soyuz). During the joint space-flight activities, two cultures from each spacecraft were exchanged. Selected duplicate cultures were maintained as controls in both the USA and the USSR. Spore ring morphology was periodically documented by photographing the specimens at approximately 12-hr intervals during the pre-, in-, and post-flight periods of the experiment. A decreased growth-rate periodicity in all but one of the eight space-flight cultures was in part attributed to the reduced temperature in the spacecraft. One of the eight cultures grew at a faster rate in the reduced temperature environment of Apollo than did the ground controls. Three of the space-flight cultures developed double spore rings during the immediate post-flight period. This anomaly was attributed to re-entry into the earth's gravity. The absence of spores in portions of one ring formed during space flight may have been caused by nutritional defects or media abnormality. Extensive studies will be required to elucidate the cause of this detect with certainty. There was no visible evidence of wedges in the cultures which would suggest naturally occurring or radiation-induced mutagenic alteration during space flight.

We have previously reported changes in the immunoresponsiveness of "T" lymphocytes following space flight. Additional data collected before and after 11 Shuttle space flights show that absolute lymphocyte numbers, lymphocyte blastogenic capability, and eosinophil percent in the peripheral blood of crewmembers are generally depressed postflight. These responses resemble those associated with physical and emotional stress and may not be related to flight per se. Additional data from Space Shuttle flights 41B and 41D, involving 11 crewmembers, indicate a postflight decrease in cells reacting with "B" lymphocyte and monocyte monoclonal antibody tags. Further, the loss of "T" lymphocyte blast capability interacts with the decreased monocyte count (correlation coefficient = 0.697). This finding implies that the previously reported loss of blastogenic capability may be a function of decreased monocyte control, as noted in several non-spaceflight related studies.

The recovery of RNA from postmortem (PM) brain tissues was quantified by molecular hybridization. RNA degradation rates postmortem were faster in mice with herpes encephalitis than with uninfected mice, but clear ribosomal peaks could be seen up to 72 hr after death. In a comparison between frontal cortex samples from neurologically normal and Alzheimer's disease cases a reduction in ribosomal, poly A, preproenkephalin, and preprosomatostatin RNA levels was observed in the Alzheimer's disease group. This general reduction may be influenced by the cause of death as well as the pathology.

Two methods for precise cell location and relocation were developed at the Cell Image Analysis Laboratory, NASA, to increase the efficiency of the cell image acquisition process. The first method uses a Zeiss Zonax with a 10 micron scanning stage and automatically records cell coordinates on 5.25-inch floppy disks. The second method uses a Digital Positioning Device with a 10 micron scanning stage, and the cell coordinates displayed on light-emitting diodes (LEDs) are recorded manually. Because of its superior speed and automation, the Zonax was selected as the method of choice. By using a Zonax for off-line cell location and another Zonax for on-line cell relocation, more than three times the number of digitized images were collected in ten months than in the previous three years. Other beneficial applications of the cell location and relocation methods were realized in photomicrography, data base verification and cytopathology.

Two nuclear segmentation methods, Baky's minimax algorithm and thresholding, were compared on a sample of 879 atypical bronchial epithelial cells in sputum. Nuclear-cytoplasmic (N/C) ratios for all cells were determined by each segmentation method and compared to a visually determined value. Cells were categorized by atypia class (from metaplastic through malignant), by staining characteristics (orangeophilic and nonorangeophilic) and by method of digitization (either scanning microphotometry or video system). The method of digitization was confounded by subject differences. The results indicated that with most classes of atypia, N/C ratios determined by minimax were closer to the visually derived values than were those of thresholding, particularly with orangeophilic cells. Both methods become progressively less accurate, as compared to the visual procedure, as the degree of atypia increases.

The possibility of significant alterations in the microbial populations inhabiting the integument and upper respiratory tract of space flight crew members has been proposed by various authors. The Apollo-Soyuz Test Project (ASTP), a unique space flight in which two teams of crew members from different geographical areas joined in space, presented an unusual opportunity to evaluate in-flight cross-contamination and other anomalous behavior of the microbial populations. Accordingly, the medically important microbes recovered from the five (3 USA and 2 USSR) ASTP crew members before and after flight were evaluated in relation to specific theoretical alterations. The phenomenon of "simplification", in which the number of different types of species is reduced during spaceflight, did not occur within the population of medically important micro-organisms. Spontaneous post-flight illness due to infectious agents ("Microbial Shock") was also absent. Intracrew transfer of pathogens was established, but intercrew transfer was absent. Dysbacteriosis, in which sampled areas are flooded with unusually large numbers of a single type of micro-organism, was not demonstrated although there was a significant increase in the incidence of gram-negative rods in the oral cavities of the two cosmonauts. The importance of all of these and other observations of the medically important micro-organisms recovered from ASTP crew members are explored with respect to past and future space flights.

Peripheral circulating lymphocytes were separated from astronaut blood samples three times before and two times after the first four US Space Shuttle flights. The ability of the in vitro T lymphocytes to respond to Phytohemagglutinin by blastogenesis was found to be reduced for each crewmember following spaceflight. In addition, the astronauts experienced a postflight increase in neutrophils and a decrease in eosinophils. These postflight changes in leukocytes are shown to increase with subjectively-evaluated increases in the incidence of inflight stress, indicating that stress, and not hypogravity, is likely to be the major effector of these changes.

Spores of Bacillus subtilis HA 101 and the DNA polymerase I-defective mutant HA 101 (59) F were exposed to selected wavelengths of solar ultraviolet light and space vacuum during the return of Apollo 16. In addition, coliphage T7 suspensions were exposed to solar ultraviolet radiation as part of the Microbial Response to Space Environment Experiment. Optical filters were employed to provide different energy levels at wavelengths 254 nm and 280 nm. Dose-response curves for lethal and mutagenic effects were compared with ground-based data. A close parallel was observed between the results of solar radiation and ground tests with spores of the two strains. However, significantly greater inactivation of T7 bacteriophage was observed after exposure to solar ultraviolet radiation.

Fever of unknown origin (FUO) is a syndrome characterised by prolonged, unexplained fever associated with non-specific signs of illness such as lethargy, inappetence and weight loss. This paper reviews the details of 63 horses affected by FUO. The cause was found to be infection in 43 per cent of the cases, neoplasia in 22 per cent, immune-mediated diseases in 6.5 per cent and miscellaneous diseases in 19 per cent; the cause remained undiagnosed in 9.5 per cent.

Nine biological species, including viruses, bacteria, fungi, and nematodes, were exposed to various combinations of space vacuum, galactic radiation, and solar UV light during the Apollo 16 space flight. No major changes in number of surviving cells occurred, permitting detailed genetic and somatic studies of returned test subjects. To enable dose-response studies, solar UV was employed as a mutagenic source with cells exposed to full sunlight or to components of the UV spectrum at peak wavelengths of 254, 280, and 300 nanometers over a range of energy levels. Proper in-flight UV irradiation monitoring required the development of a potassium ferrioxalate actinometer and an anaerobic photographic emulsion dosimeter which were tested for the first time in space. Studies of the mutagenic activity of cosmic-ray particulate radiation environment required measurement of its components with several lithium fluoride thermoluminescent dosimeters and a package of passive nuclear-track detectors capable of recording high-energy multicharge particles. These detectors included cellulose nitrate, Lexan, Ilford G5, and silver chloride crystals. The nuclear track detectors measured the incident heavy particles with the recorded spherical fluences with LET350,H2O100 keV x micrometers-1 to be 19.3 +/- 1.8 particles cm-2. This value was found to be lower than that recorded by detectors located in the Biostack and the passive personnel dosimeters worn by the astronauts, suggesting a somewhat greater average shielding.

A cytopathic effect caused by the inoculation of some cell cultures with cerebrospinal fluid (CSF) taken from neurological and psychiatric cases was identified by Tyrrell et al. in 1979. Initial characterization suggested that the responsible agent was a particle 50 to 100 nm diameter that was ether stable and unaffected by the inhibition of DNA synthesis.

Intracerebral infection of mice with HSV-1 was found to produce a 2-3-fold increase in dopamine and serotonin metabolism in cortex, striatum, diencephalon and brain stem. Neurochemical markers of GABA and acetylcholine neurones, and neurotransmitter receptor binding sites were unchanged. The immunohistochemical distribution of virus antigen revealed high levels of immunoreactivity in s. nigra, ventral tegmental area, locus coeruleus and dorsal raphe nucleus, whilst other areas of brain stem were clear of virus antigen. The changes in monoamine metabolism observed in experimental HSV encephalitis may be related to the concentration of virus in monoamine neurones.

This paper reports an experiment designed to demonstrate that the calf lung can be sensitized to a specific respirable challenge following parenteral immunization with a nonliving antigen (human serum albumin). The possibility that immune-mediated injury could subsequently interfere with nonspecific mucosal defenses was also investigated by infecting calves with Pasteurella haemolytica after the antigen challenge and assessing pulmonary clearance of the organism. The results indicated that specific aerosol challenge produces reversible signs of respiratory hypersensitivity and that persistence of incidental infection in the upper respiratory tract is potentiated. Since the calves were sensitized by an immunization regime which imitated conventional vaccination, this study highlights the potential dangers of inactivated parenteral respiratory vaccines.

The complete nucleotide sequence of a 1957 bp DNA fragment containing the dihydrofolate reductase gene (DFR1) of the yeast Saccharomyces cerevisiae is presented. Within this region a single open reading frame of 633 base pairs was found which is capable of encoding a 211 amino acid residue protein with a calculated Mr of 24,233. The amino acid sequence derived from the yeast DFR1 gene shows limited homology with sequences from both eukaryotic and non-eukaryotic DHFR enzymes. Northern blot hybridization reveals that the mRNA from this gene is a 900 base polyadenylated transcript. Yeast strains containing the cloned DFR1 gene on multicopy number shuttle vector plasmids show dramatically enhanced methotrexate resistance. Consensus DNA sequences responsible for RNA polymerase II interaction and general amino acid control in S. cerevisiae are located within the 5'-noncoding region with respect to the open reading frame. The DNA fragment containing these sequences has been shown to be necessary for DFR1 gene expression in both S. cerevisiae and E. coli.

The mineralogy and chemistry of oxidate facies sediments associated with a Solomon Island cupriferous pyrite deposit are described. Systematic variations in sediment composition are consistent with the gradual imposition of an oxidising environment on a pool of exhaled solution lying in a topographic depression on the sea floor. Manganese is first precipitated in the Mn2+ oxidation state as pyrochroite, γMn(OH)2. With later seafloor weathering and diagenesis, this oxidises initially to the Mn3+ intermediate minerals manganite (γMnO.OH) or, in the presence of iron hydroxides, to groutite (αMnO.OH). Subsequently, these oxidise further to Mn4+ as the βMnO2 dimorphs pyrolusite or ramsdellite, respectively. Todorokite (δMnO2) is indicative of more oxidising conditions and is found in the upper horizons of the manganiferous sediment. It is invariably non-stoichiometric in composition and its Mn2+/Mn4+ ratio is a direct function of the Eh prevailing during its precipitation. Adsorption of Na+, K+, Ca2+ and Ba2+ions at the time of formation stabilises the todorokite structure and provides an explanation for its persistence (with its Mn2+ions) in association with the completely oxidised Mn4+ mineral, βMnO2, pyrolusite. The enrichment of Cu, Zn and Pb in manganiferous sediments from both pelagic and exhalative environments is associated with the occurrence of goethite. The enrichment of K, Ba and Ca in manganiferous sediments from a similar range in environments is associated with the occurrence of todorokite. Both the mineralogy and trace element characteristics of a manganiferous sediment are thus a function of the environment of deposition rather than the ultimate source of the metals concerned. The trace element contents of manganiferous “floaters” should therefore only be used as an indicator of related sulphide mineralisation in the presence of other favourable factors.

SUMMARYChlorine dioxide, bromine chloride and iodine were compared with chlorine as virucidal agents. Under optimal conditions all disinfectants were effective at low concentrations, but each disinfectant responded differently to acidity and alkalinity. Disinfection by chlorine was impaired by the presence of ammonia, but the other disinfectants retained much of their potency. Disinfection of poliovirus by iodine resulted in structural changes in the virions as seen by electron microscopy, but the other disinfectants were able to inactivate poliovirus without causing any apparent structural changes.

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During the Apollo 16 space flight, in the experiment system M-191, (microbial response to space environment) spores of Bacillus subtilis 168 were exposed to space vacuum or solar UV irradiation with a peak wavelength of 254 nm or both. The effects of these space factors on the colony-forming ability of the spores were studied. It was found (i) that space vacuum alone did not affect the survival of pre-dried spores; (ii) that space vacuum in combination with solar UV irradiation with a peak wavelength of 254 nm had a synergistic effect, which may by attributed to a UV supersensitivity of the spores during vacuum exposure. These results agreed with findings of simulation experiments on earth. It was concluded that air dried spores may survive exposure to space vacuum if shielded against solar UV irradiation.

Tire traction on wet runways, possible improvement via jets mounted ahead of tires and pavement grooving

During the Apollo 16 space flight, in the experiment system M-191, (microbial response to space environment) spores of Bacillus subtilis 168 were exposed to space vacuum or solar UV irradiation with a peak wavelength of 254 nm or both. The effects of these space factors on the colony-forming ability of the spores were studied. It was found (i) that space vacuum alone did not affect the survival of pre-dried spores; (ii) that space vacuum in combination with solar UV irradiation with a peak wavelength of 254 nm had a synergistic effect, which may by attributed to a UV supersensitivity of the spores during vacuum exposure. These results agreed with findings of simulation experiments on earth. It was concluded that air dried spores may survive exposure to space vacuum if shielded against solar UV irradiation.