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Biomedical subjects

W Franklin

Publications and source records attributed to W Franklin.

At least 55 records · Page 3Linked to original sources

Metabolism of 6-nitrochrysene by intestinal microflora.

Since bacterial nitroreduction may play a critical role in the activation of nitropolycyclic aromatic hydrocarbons, we have used batch and semicontinuous culture systems to determine the ability of intestinal microflora to metabolize the carcinogen 6-nitrochrysene (6-NC). 6-NC was metabolized by the intestinal microflora present in the semicontinuous culture system to 6-aminochrysene (6-AC), N-formyl-6-aminochrysene (6-FAC), and 6-nitrosochrysene (6-NOC). These metabolites were isolated and identified by high-performance liquid chromatography, mass spectrometry, and UV-visible spectrophotometry and compared with authentic compounds. Almost all of the 6-NC was metabolized after 10 days. Nitroreduction of 6-NC to 6-AC was rapid; the 6-AC concentration reached a maximum at 48 h. The ratio of the formation of 6-AC to 6-FAC to 6-NOC at 48 h was 93.4:6.3:0.3. Interestingly, compared with results in the semicontinuous culture system, the only metabolite detected in the batch studies was 6-AC. The rate of nitroreduction differed among human, rat, and mouse intestinal microflora, with human intestinal microflora metabolizing 6-NC to the greatest extent. Since 6-AC has been shown to be carcinogenic in mice and since nitroso derivatives of other nitropolycyclic aromatic hydrocarbons are biologically active, our results suggest that the intestinal microflora has the enzymatic capacity to generate genotoxic compounds and may play an important role in the carcinogenicity of 6-NC.

Adult↗

Microbial metabolism of polycyclic aromatic hydrocarbons: isolation and characterization of a pyrene-degrading bacterium.

Microbiological analyses of sediments located near a point source for petrogenic chemicals resulted in the isolation of a pyrene-mineralizing bacterium. This isolate was identified as a Mycobacterium sp. on the basis of its cellular and colony morphology, gram-positive and strong acid-fast reactions, diagnostic biochemical tests, 66.6% G + C content of the DNA, and high-molecular-weight mycolic acids (C58 to C64). The mycobacterium mineralized pyrene when grown in a mineral salts medium supplemented with nutrients but was unable to utilize pyrene as a sole source of carbon and energy. The mycobacterium grew well at 24 and 30 degrees C and minimally at 35 degrees C. No growth was observed at 5 or 42 degrees C. The mycobacterium grew well at salt concentrations up to 4%. Pyrene-induced Mycobacterium cultures mineralized 5% of the pyrene after 6 h and reached a maximum of 48% mineralization within 72 h. Treatment of induced and noninduced cultures with chloramphenicol showed that pyrene-degrading enzymes were inducible in this Mycobacterium sp. This bacterium could also mineralize other polycyclic aromatic hydrocarbons and alkyl- and nitro-substituted polycyclic aromatic hydrocarbons including naphthalene, phenanthrene, fluoranthene, 3-methylcholanthrene, 1-nitropyrene, and 6-nitrochrysene. This is the first report of a bacterium able to extensively mineralize pyrene and other polycyclic aromatic hydrocarbons containing four aromatic rings.

Biodegradation, Environmental↗

Childhood Ki-1 lymphoma presenting with skin lesions and peripheral lymphadenopathy.

We describe a large-cell lymphoma of activated lymphoid cells in six children and adolescents. The presenting clinical features of regressing skin lesions and peripheral lymphadenopathy, sinus infiltration of lymph nodes, and infrequent tumor cell erythrophagocytosis resulted in initial diagnoses of malignant or regressing atypical histiocytosis in five cases. Binucleate and multinucleate tumor cells, sometimes with prominent eosinophilic nucleoli, resembled Reed-Sternberg (RS) cells and occasionally were found in a cytoarchitectural milieu that was consistent with a diagnosis of Hodgkin's disease (HD). The tumor cells did in fact express the HD-associated antigen Ki-1, but unlike most types of HD, the RS-like cells expressed common leukocyte antigen and were negative for Leu-M1. A T cell origin for the malignant cells was demonstrated with monoclonal antibodies in two cases, by focal staining for nonspecific esterase in one case, and by rearrangement of the beta-chain genes for the T cell receptor in a fourth case. These studies provide further evidence that some cases previously interpreted as malignant or regressing atypical histiocytosis and some types of HD are actually T cell disorders.

Adolescent↗

Metabolism of nitropolycyclic aromatic hydrocarbons by human intestinal microflora.

Anaerobic bacterial suspensions from human and rat feces and intestinal contents, and pure cultures of anaerobic bacteria metabolized 1-nitropyrene and 6-nitrobenzo[a]pyrene to 1-aminopyrene and 6-aminobenzo[a]pyrene, respectively. The metabolites were isolated by reversed-phase high performance liquid chromatography and identified by comparison of their chromatographic and mass spectral properties with those of authentic compounds. The results suggest that anaerobic intestinal bacteria could play a significant role in the metabolism of potentially carcinogenic nitropolycyclic aromatic hydrocarbons.

Anaerobiosis↗

Circulating eosinophil colony-forming cells in pure eosinophil aplasia.

Using a methylcellulose clonal culture method, we found eosinophil colony-forming cells in the blood of two patients: a 46-year-old white woman with a long history of urticaria and allergic rhinitis and complete absence of eosinophils secondary to IgG-mediated and complement-mediated destruction of her eosinophils; and a white woman with a history of allergic rhinitis and asthma and a complete absence of eosinophils in her peripheral blood. Addition of the patients' plasma or IgG to cultures of peripheral blood mononuclear cells derived from normal persons or the patients inhibited formation of eosinophil colonies without influencing colony formation in other hemopoietic cell lineages. In contrast, normal plasma or IgG had no effect on the formation of eosinophil colonies. That the IgG-mediated cytotoxic activity of eosinophils prevents the expression of an apparently normal eosinophilopoietic potential suggests an autoimmune basis for the eosinophil aplasia.

Agranulocytosis↗

New methods for detection of low levels of DNA damage in human populations.

The use of a postlabeling method to characterize and to detect infrequent base modifications in DNA is outlined. This method has the advantage that low levels of DNA modifications, approximately 1 modified base per 10(5) nucleotides, can be detected. Moreover, a broad spectrum of modification can be identified by using this methodology. The basis for the method involves transfer of a radioactive phosphate from the gamma position of ATP to the 5'-hydroxyl terminus of 3'-phosphoryl nucleotides that are derived from modified DNA by appropriate nuclease digestion. The second method involves use of a defined DNA sequence within human cells. The alpha sequence is used as a probe for DNA damage to specific nucleotides. The alpha DNA sequence is reiterated approximately 300,000 times in the human genome and exists in tandem arrays. It comprises approximately 1% of the entire genome. The reiterated sequence is sufficiently homogeneous to permit its use as a probe for a site specific in DNA damage. Examples of the application of both of these methodologies to DNA damage inflicted in human cells by chemicals and ultraviolet light are provided.

Alkylating Agents↗

Metabolism of azo dyes derived from benzidine, 3,3'-dimethyl-benzidine and 3,3'-dimethoxybenzidine to potentially carcinogenic aromatic amines by intestinal bacteria.

The metabolism of a benzidine-based dye, Direct Black 38, a 3,3'-dimethylbenzidine-based dye, Direct Red 2 and a 3,3'-dimethoxybenzidine-based dye, Direct Blue 15 has been studied both in pure cultures of anaerobic bacteria and in bacterial suspensions derived from the intestinal contents of the rat. All of the pure cultures and the rat intestinal bacteria were able to reduce the azo linkages of Direct Black 38, Direct Red 2 and Direct Blue 15 with the subsequent formation of benzidine, 3,3'-dimethylbenzidine and 3,3'-dimethoxybenzidine, respectively. The metabolites of Direct Black 38, Direct Red 2 and Direct Blue 15 were isolated and identified by gas chromatography/mass spectrometry and had similar chromatographic and mass spectral properties with those of authentic standards. Results from this study indicate that in vitro anaerobic incubations of rat intestinal microorganisms were able to reduce and cleave the azo bonds of dyes derived from benzidine, 3,3'-dimethylbenzidine and 3,3'-dimethoxybenzidine to form potentially carcinogenic aromatic amines.

Anaerobiosis↗

Total absence of eosinophils in a patient with an allergic disorder.

A 45-year-old woman with a 25-year history of episodic urticaria and rhinitis had no detectable eosinophils in blood or bone marrow; levels of other leukocytes were normal. No eosinophils were found in the nasal discharge or the exudate elicited in skin windows by ragweed extract, to which the patient exhibited an immediate-type hypersensitivity response. A complement-dependent IgG-related activity in the patient's serum cytotoxically degranulated human eosinophils in vitro without affecting neutrophils. Antieosinophil activity was confirmed by the ability of a single dose of the patient's serum to suppress significantly the eosinophil counts in monkeys for up to 12 hours. This is the first description of an isolated absence of eosinophils, a condition that may present with allergic manifestations.

Adult↗

Pulmonary hemorrhage and immune-complex deposition in the lung. Complications in a patient with systemic lupus erythematosus.

A patient with systemic lupus erythematosus (LE) was admitted with an acute illness characterized by dyspnea, hemoptysis, fever, and diffuse infiltrates revealed by chest roentgenograms. An open-lung biopsy specimen showed massive intrapulmonary hemorrhage, and immunofluorescence and electron microscopic examinations showed granular deposits of IgG within the alveolar walls and pulmonary vessels. Rare, widely scattered foci of infiltration of vessel and alveolar walls by polymorphonuclear leukocytes were also observed. The patient was treated with large doses of prednisone and her condition improved, but she had a second episode of massive hemorrhage eight days after discharge despite maintenance of the prednisone therapy. Her condition again improved over several days, and she has had no pulmonary symptoms for nine months. In some instances, pulmonary hemorrhage in patients with systemic LE may be mediated by polymorphonuclear leukocytes attracted by immune-complex deposits.

Adult↗

Developmental features of speech-sound production in language-impaired children.

The speech-sound production of severely language-impaired children was monitored in a longitudinal study. In order to generalize findings, acoustical, phonemic, and clinical observation data were collected from 30 children. Results showed that speech-sound acquisition goes through a hierarchical sequence of development and that speech-sound production will deteriorate in a predictable manner depending on the pathology. The authors hypothesize a speech-sound acquisition model, SSAM, based on the development observed.

Acoustics↗