[Prevention of drug interactions and its countermeasure].
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Animals↗
Biomedical subjects
K Kitada
Publications and source records attributed to K Kitada.
Direct monitoring as well as sensitive diagnosis of Pneumocystis carinii pneumonia by the polymerase chain reaction on sputum samples.
In order to evaluate the usefulness of the polymerase chain reaction (PCR) for diagnosis and monitoring of Pneumocystis carinii pneumonia (PCP) in specimens obtained from non-invasive techniques, expectorated or induced sputa were collected from 30 patients who were tentatively diagnosed as having PCP and administered intravenous trimethoprim-sulfamethoxazole. Using appropriate criteria, 13 of these cases were diagnosed as having PCP, 12 cases were diagnosed of other pulmonary diseases, and five cases were omitted from the study according to the exclusion criteria. PCR was performed using primers based on the P. carinii 5S rRNA sequence. Pneumocystis carinii was detected in nine of the 13 defined cases (sensitivity of 69%) and in none of 12 non-PCP cases (specificity of 100%). In contrast, P. carinii was detected in only one case by microscopic examination using Diff-Quik stain. Therefore, the sensitivity of PCR was significantly higher than that observed with the stain (P < 0.05, chi 2 = 6.125). Sputum samples were also obtained from eight cases during the treatment. The eradication of P. carinii from the sputum as judged by PCR varied from three to 38 days (median 6.5 days) after the start of the treatment. Pneumocystis carinii shedding in sputum correlated with the time between initial clinical symptoms and initiation of the treatment (P < 0.05, r = 0.810), but not with the tension of PaO2 at the time of diagnosis. This preliminary study demonstrates that PCR allows early diagnosis of PCR and that close monitoring with non-invasive specimens can be performed by PCR.
Adrenal Cortex Hormones↗
cDNA sequence diversity and genomic clusters of major surface glycoprotein genes of Pneumocystis carinii.
The major surface glycoprotein (MSG) of Pneumocystis carinii plays a crucial role in the pathobiology of P. carinii, which often causes fatal pneumonia in AIDS patients. The cDNAs encoding MSG antigens were cloned from a lambda gt11 expression library of rat-derived P. carinii by immunoscreening. The cloned cDNAs constituted a gene family containing approximately 70% amino acid identity between subtypes. The diversity of MSG cDNAs was high and reflected the genomic structure of MSG genes clustered in the P. carinii chromosomes. These multiple genes may account for the high-level expression of MSG that could generate potential variations in the cell surface. Moreover, the MSG sequences have significant sequence homology to tropomyosins and myosins, suggesting physical or functional association with the membrane cytoskeleton.
Amino Acid Sequence↗
Immunochemical characterization of the carbohydrate antigens of serotype c/Lancefield group C "Streptococcus milleri".
Carbohydrate antigens of the serotype c/Lancefield group C "Streptococcus milleri" were extracted by autoclaving whole cells of the type c reference strain K51Y. The type c and group C antigen molecules were separated and partially purified by a DEAE-Sephadex A-25 column chromatography followed by Sephadex G-100 gel filtration. The purified type c antigen and group C antigen were homogeneous in the double diffusion and in the immunoelectrophoresis. The type c antigen was composed principally of glycerol, rhamnose, glucose and N-acetylglucosamine in a molar ratio of 0.22:0.27:1.00:0.48. The quantitative precipitin inhibition test indicated that N-acetylglucosamine played a major role in immunodeterminant structure. Thus, the type c antigen of "S. milleri" is a new carbohydrate type antigen and is immunochemically different from the Ottens-type antigen III found occasionally in group C streptococci. In contrast, the group C antigen preparation contained a high proportion of N-acetylgalactosamine in addition to glycerol, rhamnose, glucose and N-acetylglucosamine, and the N-acetylgalactosamine residue was involved in the immunodominant epitope, being in good agreement with the previously proposed chemical structure of the group antigen. N-acetylgalactosamine was detected in the autoclaved extracts of a nontypeable/group C strain but not of a type c/ungroupable strain.
Acetylglucosamine↗
A multicopy suppressor gene of the Saccharomyces cerevisiae G1 cell cycle mutant gene dbf4 encodes a protein kinase and is identified as CDC5.
We have isolated a multicopy suppressor of the temperature-sensitive growth phenotype of organisms carrying mutations of DBF4, a gene that is required for the initiation of chromosomal DNA replication in Saccharomyces cerevisiae and that interacts with the CDC7 protein kinase. Nucleotide sequence analysis of the suppressor gene, provisionally named MSD2, revealed an open reading frame encoding a protein with a calculated M(r) of 81,024, with amino acid sequence similarity to the catalytic domains of protein kinases. Both genetic linkage and complementation analyses indicated that MSD2 is identical to the cell division cycle gene CDC5. An activity that phosphorylated exogenously added casein was immunoprecipitated by antiserum against a TrpE-Cdc5 fusion protein from lysates of wild-type cells containing CDC5 on a multicopy plasmid but not of cells bearing a small deletion in the predicted protein kinase domain of CDC5 on the plasmid. Deletion of CDC5 was lethal and resulted in a dumbbell-shaped terminal morphology, with the nuclei almost divided but still connected. Consistent with the function at the G2/M boundary, the CDC5 transcript accumulated periodically during the cell cycle, peaking at the G2/M boundary. CDC5 on a multicopy plasmid also suppresses temperature-sensitive cdc15, cdc20, and dbf2 mutations which affect mitosis during the cell cycle.
Alleles↗
Pneumocystis carinii pneumonia monitored by P. carinii shedding in sputum by the polymerase chain reaction.
This study investigated the efficacy of applying the polymerase chain reaction (PCR) technique to the monitoring of therapy to P. carinii pneumonia (PCP). The PCR method was sensitive enough to determine P. carinii shedding in sputum samples which was not detectable by Diff-Quik (International Reagent Corp., Kobe, Japan) stain. By PCR, P. carinii disappeared in sputa on days 8 to 15 after treatment. Clinical improvements correlated with the loss of detectable P. carinii. This study represents a potential usefulness of PCR to monitor P. carinii shedding in sputum during treatment.
Adult↗
Enzymatic differentiation and biochemical and serological characteristics of the clinical isolates of Streptococcus angiosus, S. intermedius and S. constellatus.
Of the 29 'Streptococcus milleri' strains tested, all thirteen Streptococcus intermedius (DNA homology group 2) strains but none of the thirteen Streptococcus anginosus (group 1) strains produced beta-N-acetylglucosaminidase, beta-N-acetylgalactosaminidase, alpha-N-acetylneuraminidase, beta-galactosidase, alpha-glucosidase, and hyaluronidase. The three Streptococcus constellatus (group 3) strains produced only the latter two. Glycosidase production divided 274 clinical isolates into 103 S. anginosus, 101 S. intermedius, and 70 S. constellatus strains. Generally, strains of S. anginosus and S. intermedius were non-beta-haemolytic. API II and biotype Ia (lactose positive), but the former contained almost all API III strains and belonged to Lancefield group A/serotype a (A/a), -/b, C/c, -/d, -/e, F/f or G/k, and the latter included most of biotype IId (lactose negative) and serovar -/g, -/h, -/i or -/j. S constellatus strains were beta-, alpha- or gamma-haemolytic, of API I or II but mostly biotype Ib (lactose negative), and of F/- or -/b. S. intermedius was a major member of the oral isolates. Non-oral isolates were virtually all S. anginosus (mainly urogenital isolates) or S. constellatus (the other systemic isolates).
Adult↗
Temperature-sensitive cdc7 mutations of Saccharomyces cerevisiae are suppressed by the DBF4 gene, which is required for the G1/S cell cycle transition.
When present on a multicopy plasmid, a gene from a Saccharomyces cerevisiae genomic library suppresses the temperature-sensitive cdc7-1 mutation. The gene was identified as DBF4, which was previously isolated by complementation in dbf4-1 mutant cells and is required for the G1----S phase progression of the cell cycle. DBF4 has an open reading frame encoding 695 amino acid residues and the predicted molecular mass of the gene product is 80 kD. The suppression is allele-specific because a CDC7 deletion is not suppressed by DBF4. Suppression is mitosis-specific and the sporulation defect of cdc7 mutations is not suppressed by DBF4. Conversely, CDC7 on a multicopy plasmid suppresses the dbf4-1, -2, -3 and -4 mutations but not dbf4-5 and DBF4 deletion mutations. Furthermore, cdc7 mutations are incompatible with the temperature-sensitive dbf4 mutations. These results suggest that the CDC7 and DBF4 polypeptides interact directly or indirectly to permit initiation of yeast chromosome replication.
Alleles↗
Serological and biological characteristics of "Streptococcus milleri" isolates from systemic purulent infections.
Ninety-one Streptococcus milleri strains isolated from various systemic purulent lesions of 68 patients were examined by physiological and serological tests. Most strains formed a smooth colony (66 strains), did not form spontaneous aggregation of cells in BHI broth culture (79), were non-beta-haemolytic (alpha-35 or non-41), and belonged to biotype Ia (49) or Ib (34) and to API taxa S. milleri I (41) or II (38). Almost all of the beta-haemolytic strains as well as two-fifths of the non-beta-haemolytic belonged to API taxon I; strains of API taxa II and III were non-beta-haemolytic and non-haemolytic, respectively. Two-fifths (38) of the isolates belonged to one of eight serotypes, a-g and k, and more than half (47) to Lancefield groups A, C, F or G, the most frequent being type b (19) and group F (33). Fifteen strains carried simultaneously type a/group A, b/C, c/C, e/G, f/F or k/G antigens. Nineteen were neither typable nor groupable. All the 38 serotypable isolates were non-beta-haemolytic and not members of API taxon III, and were serologically and physiologically similar to oral S. milleri. The isolates from various infected sites--sputum, thorax, abdomen, urogenitalia, skin, eye and dental--exhibited distinct combinations of biological and serological properties. These results suggest that serotyping, haemolytic properties and API taxon, and their combinations, would be useful methods to trace oral S. milleri in systemic infections.
Abdomen↗
[Detection of Pneumocystis carinii with DNA amplification].
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Adult↗
Lactose-sensitive and -insensitive cell surface interactions of oral Streptococcus milleri strains and actinomyces.
Of 158 oral Streptococcus milleri strains, 46 exhibited cellular coaggregation with the reagent strains of the actinomyces coaggregation groups A, B, and/or E. All but 1 of the 33 serotype b, e, f/F, and k/G strains belonged to streptococcus coaggregation group 2, and only 14 strains of limited seroclasses (g, i, Lancefield group F, or untypeable) appeared to be members of group 5, 3, or 4 (10, 3, and 1 strain, respectively). Thus, S. milleri infrequently exhibits lactose-inhibitable coaggregation with actinomyces.
Actinomyces↗
Adherence of oral "Streptococcus milleri" cells to surfaces in broth cultures.
Cells of representative strains of oral "Streptococcus milleri" firmly adhered to glass surfaces when grown in glucose broths as well as in fructose and sucrose broths. Cellular adherence occurred on saliva-coated glass surfaces as well as uncoated surfaces, but the cells of only a few (6 of 69) tested adherent strains agglutinated upon the addition of human whole-saliva supernatant. Thus, the firm adherence of growing "S. milleri" cells is independent of sucrose and salivary macromolecules. Two macroscopic forms of cell adherence were observed: one was a coarse-granule type and one was a tiny-granule type covered with a thin homogeneous membranous material. Scanning electron microscopy revealed that, in both types, a stringy substance interconnected the cells and connected the cells to glass surfaces, with amorphous flocklike materials present in the intercellular space. Of the 154 tested strains, 128 were adherent, of which 90 were firmly and extensively (+2 or +3) adherent. Most strains of the serovars f/F, g, h, i, j, g-, and gj- were extensively adherent. Generally, cells of the more strongly adherent strains were more hydrophobic and spontaneously aggregating. However, there also existed a few hydrophilic and nonaggregating but extensively adherent strains. The presence of trypsin or pronase completely inhibited the adherence of some strains (mostly nonaggregating) but did not at all inhibit that of others (mostly aggregating). The adhering groups did not significantly differ in their cell surface hydrophobicities. Therefore, at least two factors, one proteinaceous and one nonproteinaceous, appear to be principally involved in the firm surface adherence of "S. milleri."
Bacterial Adhesion↗
Detection of Pneumocystis carinii sequences by polymerase chain reaction: animal models and clinical application to noninvasive specimens.
Pneumocystis carinii is a eukaryotic microbe which causes fatal pneumonia in patients with AIDS. Oligonucleotide primers were used to amplify the 5S rDNA sequence of P. carinii by the polymerase chain reaction (PCR) in various clinical and animal samples. Of 35 independent lung specimens tested, PCR detected the P. carinii sequence in all 23 cases which were known to be P. carinii infected, i.e., 15 from mice, 1 from rat, 3 from human autopsy, and 4 from biopsy of AIDS patients by needle aspiration. The results were consistent with clinical and microscopic diagnosis. The detection was highly sensitive and specific. Direct sequencing of these amplified DNAs revealed homogeneity of 5S rDNA sequences of independent isolates from mice, rats, and humans. Preliminary trials manifested efficacy of the PCR method to detect P. carinii sequences in induced sputum or blood from AIDS patients, the latter case suggesting that P. carinii might enter peripheral blood via phagocytosis or direct intrusion. Development of less-invasive or noninvasive PCR diagnostic techniques to detect P. carinii infection would greatly facilitate therapeutic and prophylactic management of P. carinii pneumonia.
Acquired Immunodeficiency Syndrome↗
Cloning and characterization of DST2, the gene for DNA strand transfer protein beta from Saccharomyces cerevisiae.
The gene encoding the 180-kDa DNA strand transfer protein beta from the yeast Saccharomyces cerevisiae was identified and sequenced. This gene, DST2 (DNA strand transferase 2), was located on chromosome VII. dst2 gene disruption mutants exhibited temperature-sensitive sporulation and a 50% longer generation time during vegetative growth than did the wild type. Spontaneous mitotic recombination in the mutants was reduced severalfold for both intrachromosomal recombination and intragenic gene conversion. The mutants also had reduced levels of the intragenic recombination that is induced during meiosis. Meiotic recombinants were, however, somewhat unstable in the mutants, with a decrease in recombinants and survival upon prolonged incubation in sporulation media. spo13 or spo13 rad50 mutations did not relieve the sporulation defect of dst2 mutations. A dst1 dst2 double mutant has the same phenotype as a dst2 single mutant. All phenotypes associated with the dst2 mutations could be complemented by a plasmid containing DST2.
Amino Acid Sequence↗
A survey of Pneumocystis carinii infection in research mouse colonies in Japan.
To determine the frequency of Pneumocystis carinii infection in mouse colonies maintained for biomedical research in medical colleges or medical faculties in universities in Japan, 409 nu/nu mice were sent to 43 animal facilities from a P. carinii-free colony. The animals were housed for 6 months in groups of 3 to 10 animals per room, and examined for the presence of parasites and infection. Colonies in 10 (24.4%) of 41 facilities were positive for the infection. Of 383 animals in 69 rooms, the organism was detected in 66 (17.2%) animals in 13 (18.8%) rooms. The difference in the proportion of rooms where mice were positive for P. carinii is clearly seen among these three groups; SPF mouse rooms (4 of 38 rooms, 10.5%), SPF mouse rooms with breeding units (5 of 25 rooms, 20.0%) and conventional mouse rooms (4 of 6 rooms, 66.7%). The survey indicates that strict housing arrangements and husbandry techniques are necessary to keep SPF mice free from P. carinii infection.
Animal Husbandry↗
Secretion of killer toxin encoded on the linear DNA plasmid pGKL1 from Saccharomyces cerevisiae.
By the kar1-mediated cytoduction, linear double-stranded DNA plasmids pGKL1 and pGKL2, encoding killer toxin complex, have been successfully transferred to the recipient strains with about 30% frequency. The killer toxin was found to be secreted through the normal yeast secretory pathway by introducing pGKL plasmids into the several Saccharomyces cerevisiae sec mutants and examining the secretion of killer toxin. S. cerevisiae cells, harboring newly isolated deletion plasmid pGKL1D, expressed only the 28K protein among three killer subunits, and secreted the 28K subunit at a level of zero to 20% efficiency of the cells containing intact pGKL1 plasmid. These data indicated that subunit interaction (cosecretion) of killer proteins is required for the efficient secretion of 28K subunit. The 28K precursor protein was found to translocate across the canine pancreatic endoplasmic reticulum membrane under the direction of its own signal peptide in vitro without any other subunits. From kex2 mutant cells harboring pGKL1 plasmid, the 97K subunit, and its precursor 128K protein were not secreted, however, the 28K subunit was secreted in the same amount as that secreted from KEX2 cells. These lines of evidence suggest that the final assembly of killer toxin complex after KEX2 site of Golgi apparatus is not essential for the secretion of 28K subunit, and therefore, that putative interaction between 128K protein and 28K subunit for the transport between endoplasmic reticulum and Golgi apparatus may be required for the efficient secretion of 28K subunit.
Animals↗
Cytoprotection by histamine in rat gastric mucosa.
The effects of histamine on endogenous prostaglandins and on the damage caused by 0.6 N HCl were tested in rat gastric mucosa. The damage was assessed both macroscopically and microscopically. Histamine increased the prostaglandin E2 level in vivo and stimulated the synthesis of prostaglandin E2 and 6-keto-prostaglandin F1 alpha in vitro. These effects of histamine were inhibited by treatment with cimetidine beforehand. Histamine inhibited both the gross visible mucosal damage and deep necrosis caused by the intragastric instillation of 0.6 N HCl. This effect was overcome by cimetidine or indomethacin, but not by diphenhydramine. These results suggest that histamine stimulates prostaglandin synthesis and induces cytoprotection in rat gastric mucosa, perhaps with the involvement of the H2 receptor.
Animals↗
[Effects of indomethacin on cellular resistance and synthesis of prostaglandins in epithelial cells isolated from rat gastric mucosa].
This study was done to test effects of indomethacin (IND) on cell damage and prostaglandin (PG) synthesis in mucosal epithelial cells isolated from rat stomach in vitro. IND caused the cell damage in a dose-related way at concentrations over 5 X 10(-4) M. This damage was inhibited by 16,16-dimethyl PGE2 (10(-6) M). IND abolished the synthesis of PGE2, PGI2, and TXA2 at the concentration of 10(-4) M at which IND alone did not cause cell damage. The cells treated with 10(-4) M IND were significantly susceptible to damage caused by 15% ethanol compared to the cells not treated with IND. 16,16-Dimethyl PGE2 also inhibited the damage caused by IND + ethanol. These results suggest that the IND-induced susceptibility of the cells to damage is related to PG deficiency.
16,16-Dimethylprostaglandin E2↗