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Biomedical subjects

L Horn

Publications and source records attributed to L Horn.

At least 19 recordsLinked to original sources
PubMed1991

Biochemical and physiological characterization of the efrotomycin fermentation.

An efrotomycin fermentation was characterized through physical, chemical and biochemical studies. Growth of the actinomycete, Nocardia lactamdurans occurred during the first 50 h of the fermentation cycle at the expense of glucose, protein, and triglycerides. The initiation of efrotomycin biosynthesis was observed when glucose dropped to a low concentration. Upon glucose depletion, cell growth ceased and a switch in the respiratory quotient occurred. Efrotomycin biosynthesis was supported by the utilization of soybean oil and starch. Analysis of triglyceride metabolism showed that no diglycerides or monoglycerides accumulated during the fermentation. The activity of extracellular enzymes (lipase, protease, and amylase) increased during the cell growth phase and decreased significantly after 150 h. The concentrations of DNA, tetrahydro-vitamin K2 (a membrane component), and free amino acids in the supernatant increased dramatically late in the fermentation cycle (225 h), indicating massive cell lysis. During this same time period, a reduction in cellular respiratory activity and efrotomycin biosynthesis were observed.

Amino Acids↗
PubMed1989

Advances in the use of computerized gas chromatography-mass spectrometry and high-performance liquid chromatography with rapid scanning detection for clinical diagnosis.

A multi-component analytical system designed for the diagnosis of metabolic disorders is described. The urinary components are separated by a variety of chromatographic techniques, including automated amino acid analysis, high-performance liquid chromatography with diode-array detection and gas chromatography-mass spectrometry with a computerized mass spectral library search for identification of organic acids. The complete system can be used to diagnose over 100 different metabolic diseases. The usefulness of the chromatographic system is exemplified by the pre- and postnatal diagnosis of glutaric aciduria type I, the diagnosis of lysinuric protein intolerance and of alkaptonuria. Drugs and diet may cause interfering metabolites, as exemplified by glycofurol, used as a solvent for intravenous drugs, and saccharin. It is predicted that chromatography and mass spectrometry will continue to be important diagnostic tools for many years ahead.

Acids↗
PubMed1989

The EASI: a self-administered screening test for cognitive impairment in the elderly.

The Early Assessment Self Inventory (EASI), a rapid self-administered screening test for cognitive impairment in the elderly, was constructed to permit individuals to be assessed in a group or singly without examiner intervention. This paper-and-pencil device requires a fourth-grade reading level and makes minimal demands on literacy while assessing orientation, recent and remote memory, language, visual-construction, calculation, and attention. In the present study, the EASI was group-administered to 146 elderly persons attending senior centers and completed individually without examiner intervention by 19 outpatients at a memory disorders clinic. Participants were 60 to 95 years old with 5 to 18 years of education. The EASI demonstrated good internal consistency and test-retest reliability and was significantly correlated with the Mini-Mental State Exam and the Mattis Dementia Rating Scale, both widely used screening instruments. Neuropsychological measures of memory, attention, and verbal fluency correlated as well with the EASI as with the examiner-administered screening instruments, suggesting that the EASI may provide an efficient method of screening for cognitive impairment.

Aged↗
PubMed1988

Computerized 3-D reconstruction of small blood vessels from high voltage electron-micrographs of thick serial cross sections.

Morphological analysis of compartments in terms of volumes and the orientation of the cells and their nuclei within very small mesenteric arteries and arterioles is being carried out. Samples were from simultaneously sham operated and instrumented control and one-clip two kidney Goldblatt sustained (30 days) hypertensive dogs. Collection of specimens was standardized, i.e. sampling location, perfusion fixation, embedding, staining, and sectioning by methods proven to preserve in vivo dimensions. Serial thick cross sections (0.5 mu) were subjected to high voltage electromicrography (1.0 MeV) at 2500x and then linearly enlarged 3x photographically. The glossy micrographs (7500x) were made into montages and the contours of the smooth muscle layer (vascular smooth muscle), the endothelium (E), nuclei (N), and the internal lamina (IL) were digitized on a large GTCO digi-pad with input to a microcomputer (PC-Limited, Turbo) equipped with a 20 MB hard disk and coprocessor. Solid and transparent image reconstructions and computerized dissection of cell compartments were performed. Compartment volumes of vascular smooth muscle, IL, E and N, and individual cell and nuclear volumes, as well as nuclear/cytoplasmic ratios were calculated. Image reconstructions are presented. The emphasis is on methods and these are discussed in terms of useability for determining accurate microvessel morphology in health and disease, with particular emphasis on assessment of hypertrophy and hyperplasia in experimental hypertension, and architectural angiogenesis in general.

Animals↗
PubMed1986

Systematic laboratory diagnosis of human metabolic disorders.

A multicomponent analytical system for diagnosis of human metabolic disorders is overviewed. After preliminary analysis of the urine with simple chemical tests and standard clinical chemistry methods, the samples undergo a variety of chromatographic separations. Paper chromatography and thin-layer chromatography determine carbohydrates and mucopolysaccharides. Amino acids are analysed by automatic ionexchange chromatography. Gas chromatography - mass spectrometry with computerized library search is used to separate and identify organic acids, and high performance liquid chromatography with computerized diodearray detector is used to analyse metabolites of nucleic acids and other non-volatile or labile constituents. The system, gradually developed during the past two decades, is routinely used to diagnose, via its detection of pathological metabolites, around 100 different metabolic disorders. The methods may also be used to monitor the efficacy of therapeutic treatment in some of the cases where this is possible.

Chromatography, High Pressure Liquid↗
PubMed1986

Urinary excretion of N-acetyl amino acids in patients with some inborn errors of amino acid metabolism.

Urinary organic acid profiles of patients with Maple Syrup Urine Disease (MSUD), hereditary tyrosinemia and phenylketonuria (PKU) have been studied by means of capillary GC-MS-computer technique. In addition to the characteristic metabolites of these disorders, increased amounts of N-acetylleucine, N-acetylisoleucine and N-acetylvaline were found in MSUD-urine. Increased excretion of N-acetylphenylalanine occurred in PKU, and in tyrosinemia both the latter compound and increased N-acetyltyrosine excretion were observed. These results together with literature reports of similar studies on patients with other aminoacidopathies may indicate that most disorders which result in accumulation of one or more specific amino acids, will convert a small fraction of them into their corresponding N-acetyl derivative.

Acetylation↗
PubMed1984

An evaluation of Salmonella (Ames) test data in the published literature: application of statistical procedures and analysis of mutagenic potency.

We searched the published literature for Salmonella test data on some 450 chemicals. Only 137 of more than 400 articles containing original data satisfied minimum criteria for a quantitative analysis [1751 experiments, comprising data on 152 chemicals (Table 1)]. Many of these papers did not report basic information about the test protocol (Table 2). We used previously described statistical procedures (Bernstein et al., 1982) to estimate the initial slopes of the dose-response curves and corresponding standard errors. We also applied tests for significance and linear goodness-of-fit. We then used the results of these analyses to examine several issues: (1) Linearity of the low dose region of the dose-response curve. We found that the overwhelming majority of curves were linear, though ability to detect non-linearity of dose-response curves in the standard plate test is only limited. 7% of all experiments to which the goodness-of-fit test was applied were curves of increasing slope, and with a few possible exceptions, these were not obviously associated with any particular mutagens, even those generally considered to produce non-linear effects such as MNNG and EMS (Table 3). (2) Performance of the statistical test for significance. Results of the statistical test for significance of the dose-response were compared with author's opinions as to positivity. In almost all cases (94%) results of the statistical test and authors opinions were the same. In the examples of conflicting opinions, the reasons were: (a) the statistical test places more weight than do most authors on the presence of a linear dose-response; (b) most authors tend to require at least a 2-fold increase over the spontaneous background for 'significance', and (c) when the number of spontaneous revertants is small (e.g., TA1537), authors tend to require a larger increase in induced revertants than when the spontaneous background is large, whereas the statistical procedure makes no such distinction. These factors result in the statistical test tending to identify more experiments as positive than do authors, provided there is a linear dose-response, and authors tending to judge more experiments as positive when the dose-response is not linear. (3) Reproducibility. Among the 1751 experiments there were 122 data-sets (a total of 333 experiments) in which the same chemical was tested by two or more different laboratories under the same protocol. 21 of the 122 data-sets had some disagreement between experiments as to whether results were positive or negative (Table 4).(ABSTRACT TRUNCATED AT 400 WORDS)

Dose-Response Relationship, Drug↗
PubMed1983

A comparison of alternative measures of mutagenic potency in the Salmonella (Ames) test.

Both the spontaneous and the induced mutation rates in Salmonella tester strains vary among different laboratories, and also within the same laboratory over time. If there is an association between spontaneous and induced mutagenesis, a measure of mutagenic potency that incorporates the background may be more consistent than the simple measure of the induced slope. We have used the statistical procedures recently described by Bernstein et al. (1982), and a large data-base of Salmonella test results to examine the association between spontaneous and induced mutation and to compare several alternative measures of mutagenic potency. A correlation analysis indicated an association between spontaneous and induced mutation for TA98, TA1537 and TA1535; TA1538 was close to being significant. This was observed over a wide range of chemicals. In addition, for TA98, for which we observed the strongest association, we obtained a rough estimate of the relationship between slope and intercept by using least squares to fit K and p in the power curve beta = k alpha p. We then chose 3 simple potency measures: the slope, the ratio of slope to spontaneous background, and the ratio of slope to the square-root of spontaneous background. These corresponded to the range of p's estimated from the least-squares fit procedure. The reproducibility of these measures was compared and no significant differences were found. Though there were some differences in the relative potency ranking of chemicals using the different measures, they were highly correlated.

Mutagenicity Tests↗
PubMed1973

Increased carcinogenic action of dimethylnitrosamine after prior administration of carbon tetrachloride.

Rats were given a single dose of dimethylnitrosamine (DMN, 20 mg/kg body weight) alone or 42 or 60 hours after a non-lethal hepatotoxic dose of carbon tetrachloride (CC1(4)) and killed 12 months later. DMN alone produced no tumours in the kidney and a few in the liver, but when given 42 hours after CC1(4), tumours formed in the kidneys and the number in the liver was increased. When given after 60 hours, the incidence of kidney tumours was less but that of liver tumours was further increased. A larger dose of DMN (40 mg/kg) was tolerated 42 hours after CC1(4) and enhanced the number of kidney and liver tumours, the latter apparently due to an increased proportion of cholangiomata. Numerous small focal proliferations of atypical liver cells and of bile duct epithelium were observed after treatment with DMN. The incidence of these lesions in the different experimental treatments varied in a similar manner to the liver tumours.

Adenoma, Bile Duct↗