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Biomedical subjects

K C Smith

Publications and source records attributed to K C Smith.

At least 109 records · Page 6Linked to original sources
PubMed1989

Mutational spectrum analysis of umuC-independent and umuC-dependent gamma-radiation mutagenesis in Escherichia coli.

gamma-Radiation mutagenesis (oxic versus anoxic) was examined in wild-type, umuC and recA strains of Escherichia coli K-12. Mutagenesis [argE3(Oc)----Arg+] was blocked in a delta (recA-srlR)306 strain at the same doses that induced mutations in umuC122::Tn5 and wild-type strains, indicating that both umuC-independent and umuC-dependent mechanisms function within recA-dependent misrepair. Analyses of various suppressor and back mutations that result in argE3 and hisG4 ochre reversion and an analysis of trpE9777 (+1 frameshift) reversion were performed on umuC and wild-type cells irradiated in the presence and absence of oxygen. While the umuC strain showed the gamma-radiation induction of base substitution and frameshifts when irradiated in the absence of oxygen, the umuC mutation blocked all oxygen-dependent base-substitution mutagenesis, but not all oxygen-dependent frameshift mutagenesis. For anoxically irradiated cells, the yields of GC----AT [i.e., at the supB and supE (Oc) loci] and AT----GC transitions (i.e., at the argE3 and hisG4 loci) were essentially umuC independent, while the yields of (AT or GC)----TA transversions (i.e., at the supC, supL, supM, supN and supX loci) were heavily umuC dependent. These data suggest new concepts about the nature of the DNA lesions and the mutagenic mechanisms that lead to gamma-radiation mutagenesis.

Aerobiosis↗
PubMed1989

Role of ruvAB genes in UV- and gamma-radiation and chemical mutagenesis in Escherichia coli.

Escherichia coli umuC122::Tn 5 was mutagenized with N-methyl-N'-nitro-N-nitrosoguanidine to isolate mutations that block the residual gamma-radiation mutagenesis observed in umuC strains. Two of these mutations were shown by transductional mapping and plasmid complementation to map in the ruvA and ruvB genes (i.e., ruvA200 and ruvB201). Whereas ruvA200 was complemented by ruvA+ plasmids, the only other known ruvA mutation, ruvA59::Tn10 required both the ruvA+ and ruvB+ genes to show complementation. The ruvA200, ruvB201, ruvA59::Tn10 and ruvB60::Tn10 mutations all reduced gamma-radiation-induced ochre reversion [argE3(Oc)----Arg+] to about 30% of the wild-type level, and they all reduced UV-radiation-induced ochre reversion to about 15% of the wild-type level. The ruvA200 and ruvB201 mutants also showed reduced gamma- and UV-radiation mutagenesis with two other assays [hisG4(Oc)----His+ and Rifs----Rifr]. Streptozotocin mutagenesis (Rifr) was reduced to about half of the wild-type level in ruv strains, but ethyl methanesulfonate mutagenesis was normal. While the umuC strain did not show the oxygen enhancement of gamma-radiation mutagenesis, the ruvA200 strain showed an oxygen effect that was similar to that shown by the wild-type strain. When the ruvA200 mutation was combined with the umuC mutation, gamma-radiation mutagenesis was further reduced to 5% of the wild-type level and cells showed a synergistic sensitization to UV- and gamma-radiation-induced killing. A mutational spectrum analysis indicates a general depression of both umuC-dependent and umuC-independent gamma-radiation mutagenesis in the ruvA strain, which is in contrast with the site-specific reduction in gamma-radiation mutagenesis that is observed in the umuC mutant. The reduced radiation mutagenesis in the ruvA strain could not be correlated with a reduction in transcription of the recA or umuC genes.

Bacterial Proteins↗
PubMed1989

Clinical and pathologic correlations in 96 patients with panniculitis, including 15 patients with deficient levels of alpha 1-antitrypsin.

alpha 1-Antitrypsin levels were determined for 96 patients with various forms of biopsy-proved panniculitis. Fifteen of the 96 patients had alpha 1-antitrypsin deficiency, and 12 of these also had an abnormal alpha 1-antitrypsin phenotype. This group of patients showed substantial and characteristic clinical and histopathologic differences from the group of patients with normal levels and phenotypes of alpha 1-antitrypsin. Spontaneous ulceration and drainage of panniculitis lesions were much more common in patients with alpha 1-antitrypsin deficiency, and biopsy specimens from lesions of panniculitis in these patients were much more likely to show large areas of normal fat adjacent to necrotic lobular and septal areas, which contained many polymorphonuclear leukocytes and histiocytes. Destruction of elastic tissue was more frequent and extensive in patients with alpha 1-antitrypsin deficiency.

Female↗
PubMed1989

Effects of metric and harmonic rhythm on the detection of pitch alterations in melodic sequences.

Tested response time to alterations. Metric rhythm and harmonic rhythm of 13-note tonal sequences were either matched or mismatched. Metric rhythm (3/4 or 4/4 meter) was induced by dynamic accents. Harmonic rhythm was induced by implied chord progressions initiated on the first note and on either every third or every fourth note. Responses were not always faster for matched rhythms or for alterations occurring on the dynamic accent. Responses were consistently faster for sequences presented in 4/4 meter. Musically untrained Ss performed similarly to trained Ss, but were slower and more variable. Accuracy of recall on a music dictation task also favored 4/4 meter rather than matched rhythms. Coding of pitch content may have been facilitated by the structural framework of 4/4 meter rather than by expectancies arising from the match of temporal and pitch organization.

Adolescent↗
PubMed1988

Alpha-1-antitrypsin deficiency and panniculitis. Perspectives on disease relationship and replacement therapy.

A distinctive form of ulcerative panniculitis develops in a subset of persons with alpha-1-antitrypsin deficiency. This association may be more widely recognized if routine determinations of alpha-1-antitrypsin are performed on patients in whom neutrophilic, ulcerative panniculitis develops without specific, defined underlying causes. Therapies that appear to be of the greatest potential benefit include treatment with dapsone and alpha-1-proteinase inhibitor replacement. Astute recognition of alpha-1-antitrypsin-deficient panniculitis and assessment of response to these and other therapies will ultimately lead to a more complete understanding of the cause of this distinctive and uniquely associated disease.

Adult↗
PubMed1988

Prospective study of cutaneous phototoxicity after systemic hematoporphyrin derivative.

Hematoporphyrin derivative (HpD) is a photoactive, oncophilic substance that produces cutaneous photosensitivity as its only significant side effect. Twenty-three patients who received systemic HpD and the usual light-avoidance precautions were studied prospectively to determine the incidence and severity of cutaneous phototoxicity (CP). Seventeen of the 23 patients (74%) reported CP, including three patients (18%) who experienced blister formation. Symptoms of CP occurred for a mean duration of 6 weeks (range 5-23 weeks). Lack of compliance with restrictive photoprotective measures was felt to be a major contributing factor. Other HpD-related complications included skin hyperpigmentation, ocular discomfort, pruritus, pain at injection site, and urticaria. CP and the restrictive measures to avoid it represent major disadvantages of the clinical use of HpD.

Adult↗
PubMed1988

Genetic and phenotypic analyses indicating occurrence of the recN262 and radB101 mutations at the same locus in Escherichia coli.

The radB101 and recN262 mutations showed essentially identical phenotypes when compared in isogenic Escherichia coli strains for their effects on gamma and UV radiation survival and on conjugal recombination in a uvrA recB recC sbcB sbcC strain. Complementation tests involving attempts to reconstitute a radB+ recN+ strain by transductions between radB101 and recN262 donors and recipients, and tests involving plasmids carrying recN+ and recN::Tn1000 inserts, indicated that the radB and recN genes are identical. We suggest that the radB101 mutation now be referred to as recN2001.

Bacterial Proteins↗
PubMed1988

Different effects of recJ and recN mutations on the postreplication repair of UV-damaged DNA in Escherichia coli K-12.

Two mutations known to affect recombination in a recB recC sbsBC strain, recJ284::Tn10 and recN262, were examined for their effects on the postreplication repair of UV-damaged DNA. The recJ mutation did not affect the UV radiation sensitivity of uvrB and uvrB recF cells, but it increased the sensitivity of uvrB recN (approximately 3-fold) and uvrB recB (approximately 8-fold) cells. On the other hand, the recN mutation did not affect the UV sensitivity of uvrB recB cells, but it increased the sensitivity of uvrB (approximately 1.5-fold) and uvrB recF (approximately 4-fold) cells. DNA repair studies indicated that the recN mutation produced a partial deficiency in the postreplication repair of DNA double-strand breaks that arise from unrepaired daughter strand gaps, while the recJ mutation produced a deficiency in the repair of daughter strand gaps in uvrB recB cells (but not in uvrB cells) and a deficiency in the repair of both daughter strand gaps and double-strand breaks in uvrA recB recC shcBC cells. Together, these results indicate that the recJ and recN genes are involved in different aspects of postreplication repair.

Bacterial Proteins↗
PubMed1987

Immunohistochemical localization of substance P and enkephalin in the nucleus tractus solitarii of the rhesus monkey, Macaca mulatta.

The nucleus tractus solitarii in the monkey Macaca mulatta was found to have several subdivisions based upon cytoarchitectonics and immunohistochemistry. Subdivisions that could be identified included commissural, medial, parvicellular, dorsolateral, ventrolateral, intermediate, and interstitial. Substance P and enkephalin immunoreactivity was localized within discrete regions of the nucleus tractus solitarii, by means of the peroxidase-antiperoxidase technique. Substance P immunoreactivity occurred most frequently in the interstitial subdivision of the nucleus tractus solitarii. Moderate accumulations of substance P immunoreactivity were present in the commissural, medial, parvicellular, dorsolateral, and intermediate subdivisions, but very little was present in the ventrolateral subdivision. Enkephalin immunoreactivity followed the staining patterns of substance P; however, the amounts of enkephalin immunoreactivity were less than amounts for substance P. Following colchicine treatment, large numbers of enkephalin-immunoreactive neurons were distributed throughout all subdivisions, many being located in the parvicellular and medial subdivisions. The few substance P-immunoreactive neurons found were restricted to the parvicellular subdivision. The distribution of substance P and enkephalin immunoreactivity in M. mulatta is very similar to that described in the cat and rat. In addition, the extensive overlap of the distribution of these two putative neurotransmitters provides morphological evidence for their possible participation in the autonomic regulation within the nucleus tractus solitarii.

Animals↗
PubMed1987

Ionizing and ultraviolet radiation-induced reversion of sequenced frameshift mutations in Escherichia coli: a new role for umuDC suggested by delayed photoreactivation.

The ultraviolet (UV) and gamma radiation-induced reversion of the trpA21, trpA9813, and trpE9777 sequenced-frameshift mutations were studied in Escherichia coli K-12 with or without the plasmid pKM101. Radiation induced the reversion of all 3 frameshifts, and pKM101 enhanced this reversion 10-50-fold. Factors influencing the differential radiation revertability of frameshifts are discussed. The two most revertable frameshifts, trpE9777 and trpA9813, were used as probes to understand the role of the umuDC genes in radiation-induced frameshift reversion. Unlike the UV radiation-induced reversion of base-substitution mutations, the reversion of these frameshifts was not enhanced in a uvrA umuC strain by photoreactivation after a post-UV-irradiation incubation. The UmuDC proteins are suggested to have functions in the radiation induction of frameshifts that are more complex than are their functions in the induction of base substitutions.

Bacterial Proteins↗
PubMed1987

Comparison of the rep-38 and mmrA1 mutations of Escherichia coli.

The rep-38 and mmrA1 mutations are located very close to each other (approximately 85 min), and have been suggested to be allelic. To address this question we have compared the phenotypes of the mmrA1 and rep-38 mutants. Both the mmrA1 and rep-38 mutations blocked the enhanced killing and inhibition of postreplication repair by rich growth medium that occurs in UV-irradiated Escherichia coli K-12 uvrA cells, i.e., the mmrA1 and rep-38 strains did not show minimal medium recovery (MMR). However, phi X174 bacteriophage propagated well in mmrA1 strains, but not in rep-38 strains; a rep mutation sensitized a uvrA strain to UV irradiation, but a mmrA mutation did not. During chloramphenicol treatment, the rep-38 strain showed a larger amount of residual DNA synthesis than observed in the mmrA1 strain. The mmrA1 mutation appears to be a dominant mutation. This was determined by the failure of either plasmid pLC44-7 or episome F'KLF11, both of which carry the mmrA+ gene, to complement the Mmr- phenotype of a uvrA mmrA strain. Plasmid pLC44-7 is known to complement the rep-38 mutation, suggesting that rep-38 is a recessive mutation. Although certain of the phenotypes of the rep and mmrA mutants are similar, a number are quite different. These differences suggest that these two mutations are not allelic.

Adenosine Triphosphatases↗
PubMed1987

A model for the recA-dependent repair of excision gaps in UV-irradiated Escherichia coli.

We have tested and supported the hypothesis that, in UV-irradiated Escherichia coli, recA-dependent nucleotide excision repair only functions in the replicated portion of the chromosome (i.e., where sister duplexes exist). Using a dnaA(Ts) mutation to align the chromosomes (i.e., all rounds of DNA replication were completed, and new rounds could not be initiated), we studied the genetic control of excision repair (measured as the repair of excision gaps in DNA) in cells with unreplicated chromosomes, and also in cells with partially replicated chromosomes. The excision repair that occurred in cells with unreplicated chromosomes was recA independent, but the excision repair that occurred in cells with partially replicated chromosomes was partially recA dependent. We found no evidence of interchromosomal recombination in recA-dependent excision repair. The majority of this recA-dependent excision repair was recF dependent, and a small portion was recB dependent. The recF and recB genes are suggested to function in excision repair in a manner similar to their function in postreplication repair, i.e., in the replicated portion of a chromosome, the RecF pathway repairs gaps, and the RecB pathway repairs the DNA double-strand breaks that arise at unrepaired gaps.

Chromosomes, Bacterial↗
PubMed1987

recA-dependent DNA repair in UV-irradiated Escherichia coli.

UV-radiation-induced lesions in DNA result in the formation of excision gaps, daughter-strand gaps (DSG) and double-strand breaks (DSB), which are repaired by several different mechanisms. Postreplication repair. The recA gene is a master gene that controls all of the pathways of postreplication repair. The repair of DSG proceeds by one pathway that is also recF dependent, and one pathway that is constitutive and independent of the recF and recBC genes. A small fraction of the recF recB-independent repair of DSG is dependent upon the umuC gene, and may define an error-prone pathway of postreplication repair. Unrepaired DSG can be converted to DSB, which are normally repaired by the RecBCD pathway. However, in the recBC sbcB background, these DSB are repaired by a recF-dependent process. The RecF pathways of postreplication repair appear to utilize DNA containing a single-stranded region (either a gap or a DSB with a single-stranded end), while the RecBCD pathway appears to utilize the blunt ends of duplex DNA to promote the recombinational repair of DSB. The polA gene (especially the 5'----3' exonuclease activity of DNA polymerase I) functions in pathways of postreplication repair (both for the repair of DSG and DSB) that are largely independent of the recF gene. Nucleotide excision repair. The repair of excision gaps is independent of the recA gene in cells with unreplicated chromosomes, but is recA dependent in cells with partially replicated chromosomes at the time of UV irradiation. This recA-dependent repair of excision gaps appears to be analogous to the recF- and recB-dependent pathways of postreplication repair, i.e. the RecF pathway repairs DNA gaps, and the RecBCD pathway repairs the DSB that arise at unrepaired gaps.

DNA Repair↗
PubMed1987

Role of DNA polymerase I in postreplication repair: a reexamination with Escherichia coli delta polA.

Using strains of Escherichia coli K-12 that are deleted for the polA gene, we have reexamined the role of DNA polymerase I (encoded by polA) in postreplication repair after UV irradiation. The polA deletion (in contrast to the polA1 mutation) made uvrA cells very sensitive to UV radiation; the UV radiation sensitivity of a uvrA delta polA strain was about the same as that of a uvrA recF strain, a strain known to be grossly deficient in postreplication repair. The delta polA mutation interacted synergistically with a recF mutation in UV radiation sensitization, suggesting that the polA gene functions in pathways of postreplication repair that are largely independent of the recF gene. When compared to a uvrA strain, a uvrA delta polA strain was deficient in the repair of DNA daughter strand gaps, but not as deficient as a uvrA recF strain. Introduction of the delta polA mutation into uvrA recF cells made them deficient in the repair of DNA double-strand breaks after UV irradiation. The UV radiation sensitivity of a uvrA polA546(Ts) strain (defective in the 5'----3' exonuclease of DNA polymerase I) determined at the restrictive temperature was very close to that of a uvrA delta polA strain. These results suggest a major role for the 5'----3' exonuclease activity of DNA polymerase I in postreplication repair, in the repair of both DNA daughter strand gaps and double-strand breaks.

Chloramphenicol↗
PubMed1987

Panniculitis associated with severe alpha 1-antitrypsin deficiency. Treatment and review of the literature.

Panniculitis associated with homozygous severe alpha 1-antitrypsin deficiency was documented in three women hospitalized for painful cutaneous and subcutaneous ulcerations (severe panniculitis with spontaneous ulceration and drainage of clear or serosanguineous fluid). None had a history of trauma or infection. One patient responded rapidly and completely to treatment with dapsone. One patient, who had more extensive disease, failed to respond to prednisone plus dapsone; infusions of alpha 1-proteinase inhibitor concentrate led to resolution of her panniculitis. One patient who had severe and extensive panniculitis and pleural effusions failed to respond to corticosteroids but did well when both dapsone and infusions of alpha 1-proteinase inhibitor concentrate were added to her treatment program.

Adipose Tissue↗
PubMed1987

Alpha 1-antitrypsin deficiency panniculitis: a histopathologic and immunopathologic study of four cases.

Four cases of alpha 1-antitrypsin deficiency associated with panniculitis were reviewed. The following histopathologic characteristics were typically present: (a) large areas of normal panniculus adjacent to severe necrotic panniculitis; (b) acute panniculitis--masses of neutrophils causing necrosis and replacing fat lobules; (c) chronic inflammation and hemorrhage at the periphery of acute panniculitis; (d) focal collection and proliferation of histiocytic cells and lipophages; (e) secondary leukocytoclastic vasculitis in areas of necrosis and lymphocytic vasculitis in areas of severe inflammation, but no evidence of primary vasculitis; (f) phlebothrombosis; and (g) in partial (heterozygous) deficiency, pronounced lipophages and giant-cell replacement of fat cells. Endarteritis obliterans was noted. Direct immunofluorescence study showed C3 deposition in the blood vessels of the panniculus or dermis (or both) in all four cases, and IgM was present in the blood vessels of three. Weak granular deposits of IgM or C3 were seen at the epidermal basement membrane zone in two cases. C3 in endothelial cells of the blood vessels was detected in one case. In general, the immunoreactants in the blood vessels were not dense and probably represent secondary vasculitis. We conclude that all patients with severe panniculitis and ulceration should have alpha 1-antitrypsin levels determined. A deep excisional biopsy specimen with abundant panniculus tissue is required for histopathologic diagnosis.

Adipose Tissue↗