[Antabus in alcohol-induced liver damage].
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Biomedical subjects
Publications and source records attributed to J Hansen.
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PURPOSE: Damage to the surrounding normal brain tissue limits the amount of radiation that can be delivered to intracranial tumors. Boron neutron capture therapy (BNCT) is a binary treatment that allows selective tumor irradiation. This study evaluates the damage imparted to the normal brain during BNCT or x-irradiation. METHODS AND MATERIALS: The brains of rats with implanted 9L gliosarcomas were examined 1 year after tumor-curative doses of either 250 kV X rays or BNCT. Histopathologic techniques included hematoxylin and eosin staining, horseradish peroxidase perfusion, and electron microscopy. RESULTS: Longterm X ray survivors showed extensive cortical atrophy, loss of neurons, and widespread leakage of the blood-brain barrier (BBB), particularly around the tumor scar. In contrast, the brains and the BBB of longterm BNCT survivors appeared relatively normal under both light- and electron-microscopic examination. Intact blood vessels were observed running directly through the avascular, collagenous tumor scar. CONCLUSION: The selective therapeutic effect of BNCT is evident in comparison to x-irradiation. Both groups of animals showed no evidence of residual tumor at 1 year. However, with x-irradiation there is no therapeutic ratio and tumor eradication severely injures the remaining brain parenchyma. These observations indicate a substantial therapeutic gain for BNCT.
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The brewing yeast, Saccharomyces, carlsbergensis, is allopolyploid, derived from two diverged genomes. To obtain information about the possible origin of this yeast, we cloned two different S. carlsbergensis MET2 genes (encoding homoserine acetyltransferase). One has a nucleotide (nt) sequence identical or very similar to MET2 of Saccharomyces cerevisiae. The other has a different sequence, but was functional in S. cerevisiae. This allele was sequenced and revealed a coding region of 486 amino acids (aa). The nt sequence of the coding region showed 82% homology to S. cerevisiae MET2, while the derived aa sequences were 94% identical. Hybridization experiments to genomic DNA of different yeast strains revealed that the divergent MET2 gene had higher sequence homology to segments from type strains of S. monacensis, S. bayanus and S. uvarum than to MET2 from S. cerevisiae. Sequencing of 330 bp of a PCR-amplified fragment of MET2 from these organisms shows that the non-S. cerevisiae-like sequence from S. carlsbergensis is identical to the corresponding sequence in S. monacensis, while it is 93% homologous with S. bayanus and S. uvarum. Our results are consistent with the proposal that S. carlsbergensis originated as a hybrid between S. monacensis and S. cerevisiae. The complete identity of the MET2 fragments from S. monacensis and the S. carlsbergensis-specific MET2 allele suggests that the hybridization must have been a quite recent event.
Hydrochlorofluorocarbon 123 (HCFC 123) is one of the chemicals being considered as a replacement for the chlorofluorocarbons. Four subchronic inhalation toxicity studies from 1 to 3 months in duration have been conducted with HCFC 123. One study utilized rats and dogs, while the others were limited to rats only. The exposure levels have ranged from 300 ppm up to 20,000 ppm. Although the studies were conducted over a 14-year period, the results were consistent. In all studies, increases in liver weights were seen at 1000 ppm and above; additionally, one showed this effect at 500 ppm. Histopathological findings were minimal, consisting primarily of focal necrosis in the liver of the dogs at 10,000 ppm. Induction of peroxisomal activity, lowering of serum cholesterol and triglyceride levels, and an increase in urinary fluoride levels were also seen. The 4-hr LC50 in the rat has been reported as 35,000 ppm. At 20,000 ppm for 6 hr, the total daily dose on a concentration times time basis is almost equal to the LC50, yet, in the 4-week study, with 20 exposures at this level, there was no mortality or even marked signs of toxicity. There appeared to be no evidence for cumulative toxicity from multiple exposures in these studies. Overall, HCFC 123 appears to have a low level of toxicity by the inhalation route.
Studies of whole limb blood flow have shown that static handgrip elicits a vasodilatation in the resting forearm and vasoconstriction in the resting leg. We asked if these responses occur in the skeletal muscle vascular bed, and if so, what is the relative contribution of local metabolic versus other mechanisms to these vascular responses. Blood flow recordings were made simultaneously in the skeletal muscle of the resting arm and leg using the Xenon-washout method in ten subjects during 3 min of isometric handgrip at 30% of maximal voluntary contraction. In the arm, skeletal muscle vascular resistance (SMVR) decreased transiently at the onset of exercise followed by a return to baseline levels at the end of exercise. In the leg SMVR remained unchanged during the 1st min of handgrip, but had increased to exceed baseline levels by the end of exercise. During exercise electromyography (EMG) recordings from nonexercising limbs demonstrated a progressive 20-fold increase in activity in the arm, but remained at baseline in the leg. During EMG-signal modelled exercise performed to mimic the inadvertent muscle activity, decreases in forearm SMVR amounted to 57% of the decrease seen with controlateral handgrip. The present study would seem to indicate that vascular tone in nonexercising skeletal muscle in the arm and leg are controlled differently during the early stages of static handgrip. Metabolic vasodilation due to involuntary contraction could significantly modulate forearm skeletal muscle vascular responses, but other factors, most likely neural vasodilator mechanisms, must make major contributions. During the later stages of contralateral sustained handgrip, vascular adjustments in resting forearm skeletal muscle would seem to be the final result of reflex sympathetic vasoconstrictor drive, local metabolic vasodilator forces and possibly neurogenic vasodilator mechanisms.
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This study examined physiological and psychological changes in one solo truck driver and both drivers in a two-up truck crew during several 5-6 day round-trips to the north west of Western Australia. Endocrine catecholamine levels, cardiac sinus arrhythmia and serial reaction performance all showed progressive changes over the journey. The solo driver showed greater changes on most measures than the two-up crew and compared with control measures obtained from research assistants accompanying the drivers. The results suggest that solo drivers may experience more fatigue, impaired capacity for controlled mental effort and slowed reactions than a two-up crew.
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Although pseudomembranous colitis is relatively common following antibiotic exposure, there have been few reported cases of pseudomembrane formation involving the small intestine. Herein we report a case of pseudomembranous enteritis of the small and large intestine that occurred after antibiotic exposure. The etiologic organism appears to be Clostridium difficile, as evidenced by the characteristic pseudomembranous lesions and a positive ELISA for toxin A in an ileal tissue specimen.
BACKGROUND: Workers in the pharmaceutical industry may be exposed to many potential carcinogens. We investigated cancer morbidity in a Danish plant where enzymes, insulin, antibiotics and sex hormones were produced in substantial quantities. METHODS: Altogether 10,889 people ever employed (1964-1988) at the pharmaceutical plant were retrieved from the files of a compulsory pension fund, and followed-up in the nationwide Danish Cancer Registry (1964-1989). Site-specific standardized incidence ratios (SIR) were estimated, based on cancer rates for the national population. Information on risk factors for breast cancer, e.g. number of children, age at menarche and first delivery, obesity, and non-occupational use of sex hormones was obtained from samples of the female employees, and compared to equivalent variables from the general population. RESULTS: The overall SIR for women was significantly elevated (n = 5554; SIR = 1.2). Excess risk was particularly seen for breast cancer (n = 97; SIR = 1.5), especially in a subgroup who had started work at the factory aged 30-39 and had continued to work for 1-9 years (SIR = 2.8). The SIR was near unity for men (n = 5335); however, three men with breast cancer versus 0.4 expected were found. Lifestyle components explained only about one-quarter of the excess female breast cancers. Proxy measures of intensity of occupational exposure to sex hormones or insulin showed no association with the risk for breast cancer. CONCLUSIONS: It seems unlikely that either a single occupational factor or an unusual reproductive pattern can explain the elevated breast cancer risk. Therefore, the finding requires further study.
The ability to record sympathetic nerve activity in conscious human subjects using intraneural microelectrodes (microneurography) has proven to be a powerful clinical research tool, which has shed new light on the pathophysiology of important blood pressure problems as exemplified in studies of patients with chronic renal failure. Hypertension is present in the majority of hemodialysis patients and is a major risk factor for their excessive mortality from heart attack and stroke. Microneurographic studies indicate that there is a neurogenic component to this hypertension. In addition, severe episodic hypotension is an important complication of maintenance hemodialysis. Microneurographic studies have advanced the concept that abrupt paradoxical withdrawal of sympathetic vasoconstrictor drive is an important cause of this episodic hypotension. These microneurographic data provide the conceptual framework for systematic assessment of new therapeutic strategies.
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The yeast assimilatory sulfate reductase is a complex enzyme that is responsible for conversion of sulfite into sulfide. To obtain information on the nature of this enzyme, we isolated and sequenced the MET10 gene of Saccharomyces cerevisiae and a divergent MET10 allele from Saccharomyces carlsbergensis. The polypeptides deduced from the identically sized open reading frames (1,035 amino acids) of both MET10 genes have molecular masses of around 115 kDa and are 88% identical to each other. The transcript of S. cerevisiae MET10 has a size comparable to that of the open reading frame and is transcriptionally repressed by methionine in a way similar to that seen for other MET genes of S. cerevisiae. Distinct homology was found between the putative MET10-encoded polypeptide and flavin-interacting parts of the sulfite reductase flavoprotein subunit (encoded by cysJ) from Escherichia coli and several other flavoproteins. A significant N-terminal homology to pyruvate flavodoxin oxidoreductase (encoded by nifJ) from Klebsiella pneumoniae, together with a lack of obvious flavin mononucleotide-binding motifs in the MET10 deduced amino acid sequence, suggests that the yeast assimilatory sulfite reductase is a distinct type of sulfite reductase.
OBJECTIVE: To document the trend in arterial hypoxaemia and electrocardiographic abnormalities on the second to sixth nights after acute myocardial infarction. PATIENTS: Nineteen consecutive patients with acute myocardial infarction who were monitored continuously during the night (minimum 2300-0700) with a Holter tape recorder and a pulse oximeter. Fifteen patients were monitored for five nights, one patient for four nights, one patient for three nights, and two patients for two nights. RESULTS: Five patients had > 30 episodic oxygen desaturations of > or = 5% during the nights of monitoring and many patients had episodes with oxygen desaturations to < 80% ranging from 46% to 61% (from 7/15 to 11/18 patients) during the nights of monitoring. Constant hypoxaemia was found in 11-13% (2/15) of the patients. Simultaneous episodic hypoxaemia and episodic tachycardia was seen in 9/17 (52%) patients on the second night, 11/18 (61%) on the third, 7/15 (46%) on the fourth, 8/15 (53%) on the fifth, and 5/15 (33%) on the sixth night. Simultaneous episodic hypoxaemia and ST deviation was seen in 5/17 (29%) patients on the second night, 3/18 (16%) on the third, 4/15 (26%) on the fourth, in no patients on the fifth, and in 3/5 (20%) on the sixth night. Simultaneous occurrence of episodic hypoxaemia and arrhythmias (supraventricular, ventricular ectopy, and atrioventricular blockade) was seen in 5/17 (29%) on the second night, 4/18 (22%) on the third, 4/15 (26%) on the fourth, 2/15 (14%) on the fifth, and in no patients on the sixth night. Overall, simultaneous occurrence of episodic hypoxaemia and electrocardiographic abnormalities (episodic tachycardia, ST deviations, and arrhythmias) was seen in 11/17 patients (64%) on the second night, 13/18 (72%) on the third, 10/15 (66%) on the fourth, 8/15 (53%) on the fifth, and 7/15 (46%) on the sixth night. One patient who died of cardiogenic shock had simultaneously occurring episodic hypoxaemia and nonsustained ventricular fibrillation on the night before she died. CONCLUSION: Episodic and constant hypoxaemia are common during the first week after acute myocardial infarction. Episodic hypoxaemia was associated with electrocardiographic abnormalities in most patients. Thus, episodic nocturnal hypoxaemia may be particularly detrimental to the infarcted myocardium in the early phase after infarction; special attention should therefore be directed towards oxygenation in this group of patients.
Previous studies have produced conflicting evidence as to whether sympathetic vasoconstriction is impaired in active skeletal muscle. Because alpha 2-, not alpha 1-, adrenergic vasoconstriction is attenuated by mild acidosis, we hypothesized that alpha 2-mediated sympathetic vasoconstriction would be attenuated in contracting glycolytic muscle, which produces more acidosis than oxidative muscle. We compared effects of lumbar sympathetic nerve stimulation and alpha-adrenergic agonists on arterial pressure, femoral blood flow, and force output during contractions of oxidative or glycolytic muscles in anesthetized rats. We found that 1) sympathetic vasoconstriction was preserved during contractions of oxidative soleus muscle and during low-intensity contractions of glycolytic gastrocnemiusplantaris muscles but was abolished during maximal contractions of these glycolytic muscles; 2) this sympatholytic effect was caused by impaired alpha 2-, not alpha 1-, vasoconstriction; and 3) the increased muscle blood flow resulting from a combination of impaired vasconstriction and increased arterial pressure was paralleled by increased force of gastrocnemius-plantaris muscle contraction. Thus contraction-induced impairment of alpha 2-vasoconstriction can augment muscle blood flow and muscle contraction, but the degree of impairment depends on fiber type and intensity of muscle contraction.