Biomedical subjects
Publications and source records attributed to M Jackson.
A new antibiotic, abbeymycin, has been isolated from Streptomyces sp. AB-999F-52. The structure of abbeymycin was assigned on the basis of NMR, mass spectrometric and UV spectral data. Abbeymycin has weak activity against a limited number of anaerobic bacteria.
A complex of 18-membered macrolide antibiotics has been discovered in the fermentation broth of strain AB718C-41. The producing culture, isolated from a soil sample collected in Hamden, Connecticut, was identified as a strain of Dactylosporangium aurantiacum and was designated D. aurantiacum subsp. hamdenesis subsp. nov. The antibiotic complex was produced in a New Brunswick 150-liter fermentor using a medium consisting of glucose, soybean oil, soybean flour, beef extract and inorganic salts. Several of the antibiotics were active against sensitive and multiple antibiotic-resistant strains of pathogenic Gram-positive bacteria.
Cognitive function was assessed in two groups of hemodialysis patients exposed to relatively low concentrations of aluminum in source water used to manufacture dialysate. One group of patients (long-term group) had been on dialysis for 5 years or more, the other (short-term group) for less than 5 years. Group comparison showed no significant differences of any cognitive measure. However, calculating an index of deterioration based on the discrepancy between current reading skills and current performance on the Wechsler Adult Intelligence Scale, five patients in the long-term group and two in the short-term group could be identified as functioning below their predicted premorbid optimum level. There was no correlation between cumulative exposure to water-born aluminum and any of the measures of cognitive function in either of the groups. There was a statistically significant negative correlation between the cumulative amount of aluminum prescribed to be taken orally and performance on cognitive tests in the long-term group. This observation strengthens the case for minimizing the prescription of aluminum-containing gut phosphate binders.
The DSM-III symptoms of attention deficit disorder, residual type in adult alcoholic patients may be classified more accurately using the absolute number of symptoms reported rather than the symptom constellation required by strict DSM-III criteria.
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The metabolism of 1-nitro[14C]pyrene (14C-1-NP; 8.1 microM) was studied in cultured (20 hr) rabbit alveolar macrophages, lung tissue, and tracheal tissue. Metabolites from the incubation medium and from the macrophages and respiratory tract tissues were extracted and then analyzed and quantified by high-pressure liquid chromatography. The following metabolites were detected in the lung and tracheal tissue incubation medium: 1-nitropyrene-4,5-dihydrodiol, N-acetyl-1-aminopyrene, 1-aminopyrene, and 10-hydroxy-1-nitropyrene. Nitropyrene phenols (4-, 5-, 6-, 8- or 9-hydroxy-1-nitropyrene) and 3-hydroxy-1-nitropyrene were only detected in the lung and tracheal tissue and not in the incubation medium for these tissues. Minor amounts of 1-aminopyrene and 10-hydroxy-1-nitropyrene were detected in the macrophage incubation medium, and only minute quantities of 1-nitropyrene-4,5-dihydrodiol, 1-aminopyrene, and 10-hydroxy-1-nitropyrene were detected in macrophages. The total percentage of 1-NP metabolism was significantly greater in the lung and tracheal tissue (28.0 and 23.0% of the recovered 14C, respectively) than in the alveolar macrophages (6.3% of the recovered 14C). The tracheal tissue was found to have the highest activity both in 1-NP metabolism and intracellular metabolite concentration. A major portion of the 1-NP metabolites produced was released into the incubation medium. The majority of the metabolites produced by tracheal and lung tissue, 70 and 84%, respectively, were ethyl acetate extractable. The metabolites retained within the cells or tissues were also predominantly ethyl acetate extractable rather than water soluble (83% for the macrophages and trachea, 95% for the lung tissue). The metabolite profiles obtained demonstrate that metabolism by both nitro reduction and ring oxidation occurs in respiratory tissue, and a degree of tissue specificity in the formation of metabolites exists. Ring oxidation was demonstrated in the lung and tracheal tissue, but very little occurred in the macrophages.
In this paper we describe the construction of a Graded Difficulty Arithmetic test (GDA) consisting of 12 additions and 12 subtractions which are orally presented. The test was administered to a control group of 100 volunteer subjects with extra-cerebral neurological disorders and to two experimental groups of patients with unilateral cerebral lesions of the left and right hemisphere. In the control group performance on the GDA was found to correlate highly with other measures of verbal intelligence, namely the National Adult Reading Test, the WAIS Arithmetic subtest and the WAIS Digit Span subtest. Between group analysis showed a significant groups effect on the GDA, the left hemisphere lesion group showing greater impairment compared to the right hemisphere lesion group and the controls. Using "cut-off" scores the left hemisphere lesion group's performance was shown to be significantly worse than that of the right hemisphere lesion group, who in turn were not significantly worse than the control group.
Alveolar macrophage cultures exposed to coal fly ash vapor-coated with 1-nitropyrene were used as a model system to study the bioavailability and the uptake of a nitroaromatic hydrocarbon from coal combustion emissions. Initially, 1-nitropyrene-coated fly ash and uncoated fly ash were examined for cytotoxicity using rabbit alveolar macrophages and for mutagenicity in the Salmonella typhimurium plate incorporation assay. The results were compared to determine the effects of vapor deposition. The distribution and recovery of 1-nitropyrene from macrophage cultures treated with coated fly ash were determined by using a reverse-phase high-performance liquid chromatography-fluorescence method. 1-Nitropyrene alone was not very toxic, nor did vapor deposition of 1-nitropyrene onto coal fly ash significantly affect the toxicity of the fly ash. Most toxicity resulted from the original, uncoated fly ash particles. 1-Nitropyrene after being coated onto the particles was bioavailable in agar and aqueous culture medium. The coated fly ash showed mutagenic activity when the particles were tested directly; the uncoated fly ash did not show mutagenic activity. 1-Nitropyrene recovery from alveolar macrophage cultures exposed to the coated fly ash diminished as cell number increased. The rate of 1-nitropyrene loss was 2.7 ng/10(6) macrophages for medium and 4.1 ng/10(6) macrophages for the whole culture. The mutagenic activity recovered from these macrophage cultures also decreased with increasing cell number.
A systematic survey of in-patient accidents and injuries in an inner London hospital over 9 years established that, after incisions and overdoses, self-incineration was one of the commoner methods of violent self-harm. A case-controlled study of in-patient suicide attempts compared a series of 12 self-incinerators with 12 patients using other methods. Irrespective of method, the suicide attempt was predominantly a psychotic act of young single people with chronic, severe disorders and considerable past parasuicide, in a setting of escalating self-harm. Younger age, greater psychiatric morbidity, absence of alcoholism, a history of childhood arson, past and current self-burning were the features specific to self-incineration, which had a 25% mortality rate.
Three pregnancies at risk for late infantile metachromatic leucodystrophy have been monitored using chorionic villus biopsies. In the first of these a false negative diagnosis was made following assay of arylsulphatase A in villi. Subsequent studies have shown that this error was probably due to interference from another sulphatase in the villi, although the possibility that maternal contamination was also partly responsible could not be excluded. For reliable prenatal diagnosis of metachromatic leucodystrophy using chorionic villi it is advisable that studies with the nitrocatechol substrate are carried out on fractionated homogenates, or that the natural substrate is used. Problems may also occur when chorionic villi are used for assay of arylsulphatase B for first trimester diagnosis of Maroteaux-Lamy disease.
A new case of multiple sulphatase deficiency with onset at birth is described. The patient had many dysmorphic features and hydrocephalus, similar to one other case with early onset described in the literature. The new patient differed from the other case in having chondrocalcificans congenita, heart abnormalities and an abnormal fold of tissue present between the laryngeal inlet and the oesophagus. Excessive mucopolysacchariduria was present and there was profound deficiency of all sulphatases examined in plasma, leucocytes and cultured skin fibroblasts.
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We have carried out transcriptional measurements on several families of repeated sequences to define their expression in mouse cells. The majority of Alu family transcripts result from read-through from adjacent structural gene promoters while 20% are discrete RNA polymerase III products. Alu repeat members show preferential orientation within RNA polymerase II transcription units as evidenced by asymmetric representation of the complementary strands of the Alu family in hnRNA. We assessed whether 3 non-Alu repeated sequence families had their own promoters by strand symmetry measurements and size distribution analysis of repeat-homologous newly synthesized nuclear RNA. Transcription homologous to the R family is totally symmetric and is likely due to read-through from adjacent structural gene promoters. LLRep1 and Bam5 repeats, in contrast, exhibit consistent strand asymmetry which is suggestive that at least some members may be transcribed by their own promoters. Among 3 mouse tissues and 1 cultured cell line analyzed, no quantitative variation in the expression of any of these sequences was observed.
3-Methylcholanthrene-induced T-cell thymic lymphomas in RF mice were examined for involvement of murine leukemia virus (MuLV)-related sequences in leukemogenesis. Both the expression of MuLV-related RNA species and the organization of endogenous MuLV proviral DNA were analyzed. Of 27 primary tumors examined, only 5 exhibited elevated MuLV-related RNA species homologous to xenotropic specific env DNA. None of these RNA species hybridized with ecotropic p15E DNA sequences. Only two of these five tumors contained MuLV-like RNA species that hybridized with ecotropic MuLV long terminal repeat sequences, despite the probe's ability to detect both ecotropic MuLV and mink cell focus-inducing viral RNA. No muLV resembling mink cell focus-inducing virus whose expression could be correlated with lymphomagenesis was detected in either preleukemic thymocytes, primary 3-methylcholanthrene-induced thymic tumors, tumors passaged in vivo, or cell lines derived from tumors. Restriction endonuclease analysis of DNA from both primary tumors and cell lines failed to reveal either proviral DNA with recombinant env genes or rearrangement of endogenous MuLV proviruses. Therefore, chemically induced lymphomagenesis in RF mice appears different from the spontaneous lymphomagenic process in AKR mice with respect to the involvement of endogenous MuLV sequences.
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