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Biomedical subjects

J Horn

Publications and source records attributed to J Horn.

At least 55 records · Page 3Linked to original sources

7-Sulfooxymethylbenz[a]anthracene is an ultimate electrophilic and carcinogenic form of 7-hydroxymethylbenz[a]anthracene.

The hypothesis was tested that 7-sulfooxymethylbenz[a]anthracene (7-SBA) is an ultimate electrophilic and carcinogenic form of 7-hydroxymethylbenz[a]anthracene. In conformity with this hypothesis, 7-SBA was more carcinogenic than 7-HBA in inducing sarcomas at the site of repeated subcutaneous injection. These metabolites were individually administered to female Sprague-Dawley rats, beginning at 30 days of age, in 0.2 mumol doses given three times each week for 20 doses. One year after the first injection of 7-SBA, seven of thirteen female Sprague-Dawley rats had developed sarcomas. 7-HBA, on the other hand, had induced sarcomas at the site of injection in only two of tweleve rats. No tumors developed either in the control group given sesame oil:DMSO only or in the untreated control group. It would appear from the results summarized here that the search for an ultimate electrophilic and carcinogenic form of 7-HBA has been successful.

Animals↗

7-Sulfooxymethyl-12-methylbenz[a]anthracene is an exceptionally reactive electrophilic mutagen and ultimate carcinogen.

The hypothesis was tested that an ultimate carcinogen of 7-hydroxymethyl-12-methylbenz[a]anthracene (HMBA), a major metabolite of 7,12-dimethylbenz[a]anthracene (DMBA), is a benzylic carbonium ion generated from an exceptionally reactive aralkylating metabolite, such as an electrophilic sulfate ester. In conformity with this hypothesis, sarcomas were rapidly induced in rats following repeated subcutaneous injection of HMBA (67%) or its electrophilic sulfate ester, sodium 7-sulfooxymethyl-12-methylbenz[a]anthracene (SMBA) (100%). It would appear from the results summarized here that the search for a carcinogenic metabolite of DMBA has been successful. In addition, an aralkylating electrophilic mutagen and carcinogen has been prepared from HMBA, which is itself either an ultimate carcinogen or a direct precursor of an ultimate carcinogen, i.e., a benzylic carbonium ion.

9,10-Dimethyl-1,2-benzanthracene↗

[Physician-patient relations from the viewpoint of the surgeon].

The impressive caricatures from Dieter Hanitzsch drew attention to the changes in the state of health policy compared to earlier times. Accompanying this, different aspects which are relevant for the physician-patient relationship are depicted and the conclusion reached that the basic humanity of this relationship is always dependent on the initiative of the individual. For the reestablishment of medical credibility and medical professionality it is essential that the individual physician completes his task in an open, sincere, committed, and, above all, patient-oriented manner.

Ethics, Medical↗

1-Sulfooxymethylpyrene is an electrophilic mutagen and ultimate carcinogen of 1-methyl- and 1-hydroxymethylpyrene.

1-Hydroxymethylpyrene and 1-sulfooxymethylpyrene were tested for complete carcinogenic activity by repeated s.c. injection in groups of 12 female Sprague-Dawley rats, respectively. A dose of 0.2 mumol of either 1-sulfooxymethylpyrene or 1-hydroxymethylpyrene was administered every other weekday for 20 doses (i.e., total dose 4 mumol) to each of 12 rats, beginning at 30 days of age. Once a week the rats were weighed then palpated for the appearance of tumors. Tumor-bearing rats were sacrificed 20-50 days after the appearance of first palpable tumor. By 52 weeks, 1-sulfooxymethylpyrene had induced sarcomas at the site of injection in 58% of the rats with an average induction time of 33 weeks. By contrast, 20, 0.2 mumol doses of 1-hydroxymethylpyrene failed to induce tumors at the site of injection in a group of 12 rats. Similarly, neither of the two control groups produced tumors. The present experiment, together with previous data, strongly supports the hypothesis that 1-sulfooxymethylpyrene is either itself an ultimate carcinogen or a direct precursor of an ultimate carcinogen, the highly reactive benzylic carbonium ion, which reacts with DNA to form aralkyl-DNA adducts in a chain of events leading to malignant growth.

Animals↗

A nuclear protein factor binds specifically to the 3'-regulatory module of the long-interspersed-nuclear-element-like Dictyostelium repetitive element.

The Dictyostelium repetitive element DRE integrates in a position-specific manner upstream of tRNA genes in the Dictyostelium discoideum genome. DRE has structural similarities to the group of long interspersed nuclear elements, whose replication mechanism is poorly understood. The C-module at the 3' end of DRE encodes a regulatory cis-acting sequence that contains an RNA polymerase II promoter. This promoter directs the synthesis of RNAs that are thought to play a critical role in DRE transposition. In this study, we describe the identification of a nuclear protein factor that binds to the C-module in a sequence-specific manner. The C-module-binding factor (CMBF) recognizes three DNA sequence motifs that contain homopolymeric (dT) stretches of variable lengths, but does not bind to a standard RNA polymerase II promoter from D, discoideum. Analysis of highly CMBF-enriched fractions and glycerol gradient sedimentation of CMBF suggest that the factor exists as a monomeric 115-kDa protein. Possible roles of CMBF in DRE transposition are discussed.

Animals↗

Development of an L6 myoblast in vitro model of moniliformin toxicosis.

L6 myoblasts were used as an in vitro model to investigate the role of moniliformin and its interaction with monensin in turkey knockdown syndrome and sudden death syndromes in poultry. Cell viability and microscopic and ultrastructural alterations noted in L6 myoblasts cultured in the presence of moniliformin (0.0-0.3 microgram/microliter) were compared to those observed in parallel cultures also containing one of the following compounds: selenium (0-0.004 ng/microliter), thiamine (0-0.3 microgram/microliter), or pyruvate (0-0.46 microgram/microliter). Marked dilation of the RER, membranous whorls, glycogen deposition, membrane-bound cytoplasmic inclusions and necrosis were observed in myoblasts exposed to 0.03-0.30 microgram moniliformin/microliter medium. Supplementation of medium with thiamine and pyruvate, or selenium, provided significant protection to cells exposed to 0.0-0.3 microgram/microliter or 0.0-0.15 microgram moniliformin/microliter, respectively. Dose-dependent differences in protein and ATP production were not detected. Myoblasts grown in medium containing 0-0.15 microgram moniliformin/microliter and 7.5-50.0 microM A23187, beauvericin or monensin had degrees of cytotoxicity similar to parallel cultures receiving only an ionophore. L6 myoblasts were a useful model of moniliformin toxicosis. The findings of this study suggest cytotoxicity due to moniliformin in L6 myoblasts may be due in part to oxidative damage and altered pyruvate metabolism, and that moniliformin does not predispose myoblasts to ionophore toxicosis. This study supports the results of in vivo investigations in poultry that moniliformin and monensin do not act synergistically to induce knockdown or monensin toxicosis.

Adenosine Triphosphate↗

The effect of artificial tears on computer-assisted corneal topography in normal eyes and after penetrating keratoplasty.

PURPOSE: To examine the effect of adding artificial tears for one minute to normal eyes and eyes that have undergone keratoplasty by using computer-assisted videokeratography. METHODS: We prospectively analyzed 24 normal corneas (24 patients) chosen by random number table (reproducibility section [10 eyes], tear section [14 eyes]) as well as 14 postkeratoplasty corneas. The parametric descriptors analyzed statistically included the simulated keratometry value, surface asymmetry index, surface regularity index, power at the vertex normal, and the pupil offsets from the visual axis. Vectoral analysis was used to calculate the difference in power and axis between the simulated keratometry values before and after tear instillation. RESULTS: In normal eyes, tear instillation increased the surface asymmetry index (0.28 +/- 0.34, P = .01), changed the simulated keratometry value (0.23 diopter by 27.8 degrees), and power (0.79 +/- 0.82 diopters, P = .004) and location (0.91 +/- 0.76 mm) of the steepest point of the cornea changed. In postkeratoplasty eyes, the surface regularity index decreased (0.49 +/- 0.80, P = .04), surface asymmetry index decreased (0.37 +/- 1.03, P = .21), mean simulated keratometry value changed (1.04 diopters by 1.01 degrees), and power (0.70 +/- 2.34 diopters, P = .28) and location (1.04 +/- 1.17 mm) of the steepest point of the cornea changed. Changes were greater than the variability of the surface regularity index (0.07 +/- 0.05), surface asymmetry index (0.04 +/- 0.03), simulated keratometry value power (0.08 +/- 0.06 diopter), and axis (4.6 +/- 5 degrees). CONCLUSIONS: The addition of artificial tears to normal or regular and symmetric eyes that have undergone keratoplasty worsened symmetry and changed the power and location of the steepest point. However, the addition of artificial tears to irregular eyes that have undergone penetrating keratoplasty created a more regular and symmetric surface and significantly altered the simulated keratometry values. We recommend that corneal topography be performed before the application of artificial tears.

Adult↗

Can morbidly obese patients safely lose weight preoperatively?

BACKGROUND: Preoperative weight loss is often suggested as a means of reducing operative risk in obese patients requiring laparotomy but there are no large studies documenting that this is feasible or helpful. Although several commercial products are available that provide high levels of protein with low levels of carbohydrates in convenient liquid preparations, recommendations regarding the extent to which weight loss can be pursued preoperatively are not available. PURPOSE: To determine whether it is practical and safe to have obese patients lose weight preoperatively. PATIENTS AND METHODS: We asked 100 severely obese patients requesting gastric bypass surgery to diet before their operations. Seventy patients agreed to diet by consuming a 420 Kcal, 70 g protein liquid diet daily for at least 1 month. RESULTS: Forty-seven patients lost at least 7.5 kg (mean +/- SD 17.1 +/- 0.7). The patients who successfully lost weight preoperatively (dieters group) were significantly heavier than patients (nondieters group) who did not lose weight (251% +/- 45% of ideal body weight [IBW] versus 229% +/- 33% IBW, respectively; P < 0.01), had a significantly higher ratio of men to women, and had psychiatric evaluations and psychological test scores that suggested significantly more psychopathology. Other biosocial and medical characteristics were similar. Postoperatively, the dieters and nondieters had similar rates for morbidity. Dieters and nondieters had no differences in wound-healing complications, and subgroups who had collagen deposition measured experimentally had similar amounts of hydroxy-proline accumulation in their wounds. CONCLUSION: These results suggest that a preoperative diet program appeals more to certain subgroups of severely obese patients than to others. An aggressive preoperative weight loss program that encourages patients to lose an average of 17 kg is safe and can be accomplished practically using available commercial products.

Female↗

Imaging of exocrine pancreatic function. Investigation of the bioavailability of weak organic acids as potential pancreatic contrast agents for computed tomography.

RATIONALE AND OBJECTIVES: The feasibility of targeting iodinated contrast agents to the exocrine pancreas was investigated. Iodinated weak organic acids including succinic acid-mono-3-amino-2,4,6-triiodo- N-ethylanilide (compound I), the ethanolamine salt of N-ethylsuccinic acid-(2,4,6-triiodo-3-methylamino anilide) (compound II), and the sodium salt of 2,4,6-triiodo-3-N-ethylacetylamino-phenylpropionic acid (compound III) were studied as potential contrast agents for computed tomography (CT) of the pancreas. METHODS: An ex vivo perfusion system was used to compare pancreatic uptake of the three compounds. In vivo CT studies were conducted using domestic pigs to study potential enhancement of the pancreas after intravenous injection of the compound. RESULTS: Ex vivo perfusion studies with isolated rat pancreas demonstrated nearly identical extraction ratios of approximately 0.6 for all three compounds tested. Average iodine concentrations measured in pancreas at the end of the perfusion studies was 0.27 mg/g +/- 0.20 for compound I, 0.18 mg/g +/- 0.06 for compound II, and 0.16 mg/g +/- 0.09 for compound III. Differences in iodine concentrations retained were not statistically significant. Computed tomography studies in domestic pigs demonstrated up to 30% enhancement of the pancreas after intravenous injection of 75 and 150 mg/kg of compound II at 45 minutes. Whereas ex vivo perfusion studies indicated increasing extraction of the three compounds with increasing doses/concentrations in the perfusate, no improved contrast enhancement was observed at the higher dose level compared with the lower dose in CT. CONCLUSION: Both ex vivo perfusion studies and dose-independent enhancement levels achieved seem to indicate a transport maximum in the pancreas for the iodinated weak organic acids studied.

Anilides↗

Anti-EBNA-1 (carboxy-half) IgG antibodies as a seroepidemiological marker for Epstein-Barr virus infection.

A population of 2,024 voluntary blood donors was tested for anti-EBNA-1 IgG and anti-VCA IgG serum antibodies to define the EBV infection rate and to compare two different epidemiological markers. Initial screening was performed with a sensitive EBNA-1-IgG ELISA based on recombinant antigen (Biotest) and a VCA-IgG ELISA based on conventional antigen. Both ELISAs had concordant results in 90.4% of the sera. The infection rate was found to be 96.8%. The expected immune status VCA+/EBNA+ was observed in 98.1% of the seropositives. The comparison of sensitivity, specificity, and predictive values between the two screening assays underlines the superiority of the EBNA-1 ELISA. The marker anti-EBNA-1 IgG as detected by a sensitive ELISA (Biotest anti-EBV recombinant) is suitable for defining previous EBV infection (positive predictive value 99.8%). The high infection rate in the adult population, however, renders the supply with EBV-negative blood rather difficult.

Adult↗

A comparison of five stroke scales with measures of disability, handicap, and quality of life.

BACKGROUND AND PURPOSE: Recently much debate has arisen on the appropriateness of assessing stroke outcomes with stroke impairment scales. Our purpose was to study the relationship between long-term impairments and functional outcomes in terms of disability, handicap, and quality of life. METHODS: We studied 87 patients who had a stroke 6 months earlier. Impairments were scored on five stroke scales: the Orgogozo Scale, the National Institutes of Health scale, the Canadian Neurological Scale, the Mathew scale, and the Scandinavian Stroke Scale. Disability was assessed with the Barthel Index, handicap with the Rankin scale, and quality of life with the Sickness Impact Profile. The linear relationship between stroke scales and functional scales was assessed with correlation coefficients. We used regression analyses to explain functional health. RESULTS: The stroke scales were highly related to one another (range, r = -.85 to .92). The correlation between stroke scales and functional scales was < .70 and decreased from Barthel (mean r2 = 47.5%) to Rankin (mean r2 = 36.5%) to Sickness Impact Profile (mean r2 = 33%). Stroke scales were rather poorly correlated with patients' psychosocial conditions (mean r2 = 11.5%). Functional health status was mainly related to leg power and orientation. The standardized stroke scale weights of the explanatory items were lower than their standardized regression weights. CONCLUSIONS: Stroke scales only partly explain functional health. The impact of impairments on functional outcomes seems to be underestimated by the stroke scale weights. The correlation patterns give empirical support to the hierarchical structure of the International Classification of Impairments, Disabilities and Handicaps.

Aged↗

[Role of surgical therapy in acute pancreatitis].

Thirty-four of 44 patients with severe necrotizing pancreatitis were operated on. One patient died as a result of an undiagnosed pneumothorax. The mortality of the patients in stage II and III was accordingly 2.1% and 2.9% for the patients operated-on. In accordance with the possibilities of surgical therapy, four principles are defined. The corresponding repertoire of methods is shown. Following these principles it is necessary to individualize the methods for each patient.

Acute Disease↗