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Biomedical subjects

S Hansen

Publications and source records attributed to S Hansen.

At least 217 records · Page 12Linked to original sources

A simple method of distinguishing the bacterial viruses T3 and T7, and a critical reevaluation of their heterologous and homologous exclusion.

A method is presented allowing a clear distinction between bacterial viruses T3 and T7 by plating on selectively permissive host cells. The indicator strains are Escherichia coli cells containing either cloned pif genes (exclusively permissive for T3) or the EcoRV DNA restriction system (permissive only for T7): The efficiencies of plating of the two phages on these hosts differ by more than 8 orders of magnitude. This method was applied to reinvestigate the controversial question of mutual exclusion between T3 and T7. Under single-burst conditions, about 50% of coinfected cells (permissive for both viruses) produced T3 and T7 progeny while about 25% reproduced only T3 and about 25% only T7. The burst size of co-infected cells was slightly reduced, compared to controls infected with only one virus type. Homologous exclusion among T3 phages was also not seen; rather, there was a gene dosage effect: T3-encoded RNA polymerase activity as well as T3-specific RNA synthesis increased proportionally to the multiplicity of infection (2.5-20 plaque-forming units/cell).

DNA Restriction Enzymes↗

Chromosomal rearrangement involving chromosomes 4, 6, 11 and 11.

The case of a healthy 29-year-old woman is reported who had a history of three early spontaneous abortions. Chromosomal analysis of the mother of the patient showed a balanced karyotype of 46,XX,t(6;11) (q24; q21), whereas the chromosomes of her father were normal. The karyotype of this patient is thus a combination of a familial translocation 6;11 and a de novo translocation 4;11, which is very rare.

Adult↗

2-Phenylpyridine and 3-phenylpyridine, constituents of tea, are unlikely to cause idiopathic Parkinson's disease.

Idiopathic Parkinson's disease (PD) is likely to be caused by one or more unidentified neurotoxins, present in the environment or formed endogenously, which progressively damage dopaminergic nigrostriatal neurons. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is an experimental neurotoxin which produces biochemical and neuropathological changes in lower primates and mice and in humans inadvertently exposed to it that closely resemble those found in PD. 2-Phenylpyridine (2-PP) and 3-phenylpyridine (3-PP), both of them present in tea, are the only MPTP analogues that are known to be present in the human diet. We exposed C57 black mice, animals very sensitive to the dopaminergic neurotoxicity of MPTP, to prolonged parenteral and oral administration of large doses of 2-PP, and to prolonged parenteral administration of the N-methylated tetrahydro derivatives of 2-PP and 3-PP. The latter are closer chemical analogues of MPTP than are 2-PP and 3-PP themselves. None of these MPTP analogues lowered the contents of dopamine and its metabolites in the striatum of mice. We speculate that the neurotoxins which cause PD are unlikely to resemble MPTP structurally, and we suggest that the search for chemical causes of PD should be directed to a wider variety of compounds encountered by humans.

3,4-Dihydroxyphenylacetic Acid↗

[High-resolution MRT with increased magnetic field gradients and a 512(2)-data matrix: initial clinical experiences].

By increasing the strength of the magnetic field gradients of a whole-body imager to 9.4mT/m, it was possible to obtain spin-echo images with short echo delays and high spatial resolution. The reduction of the pixel size was effected either by decreasing the field of view or by increasing the scan matrix (512(2) pixel). To prevent loss of signal-to-noise ratio, the scan parameters had to be carefully selected. With the 512(2) matrix, the resolution could be increased without decreasing the field of view, so that backfolding artifacts were avoided. In comparison with the 256(2) matrix, the 256 x 512 matrix provided improved resolution in the frequency encoded direction without an increase in acquisition time.

Humans↗

An improved method for rapid measurement of accommodation and firing frequency of single motor units in man.

A stimulator is described producing trapezoid wave forms with accurately defined linear rise and fall at pre-determined slopes independent of the maximum current which is limited at the threshold for a motor unit recorded by discriminative electrodes. The stimulation threshold, measured in rheobase units, is directly proportional to the latency of response and is more accurately measured by sweep expansion (by computer). Thresholds to linearly rising currents of pre-selected slopes are rapidly measured and plotted on a grid calibrated to allow immediate measurement of the time-constant of accommodation.

Electric Stimulation↗

Bone marrow karyotype and prognosis in primary myelodysplastic syndromes.

Bone marrow karyotype, survival time, and the rate of progression to leukaemia were studied in 111 unselected patients with primary myelodysplastic syndromes. The 49 patients (44%) with clonal chromosome aberrations had survival time (median 29 months) similar to that found in the 62 patients with normal bone marrow karyotype (24 months, p greater than 0.10). The presence of multiple (greater than 2) abnormalities (17 patients) was strongly associated with poor prognosis, with a median survival of only 7 months (p less than 0.001). Prognostic information could be attributed to 2 specific abnormalities, del(5q) and -7: Presence of del(5q) as the sole anomaly was associated with long survival (36+ months), whereas monosomy 7 was a bad prognostic sign (6 months). The risk for leukaemia development correlated neither with the number of chromosome abnormalities nor with any particular anomaly. Our findings demonstrate the prognostic importance of quantifying the complexity of bone marrow chromosome changes. They also emphasize that different specific abnormalities convey widely different prognostic information in primary myelodysplastic syndromes.

Bone Marrow↗

Brain amino acids and glutathione in progressive supranuclear palsy.

We measured amino acid contents in autopsied brains of seven patients with progressive supranuclear palsy (PSP) and in control subjects dying without brain disease. Glutathione was also quantitated in rapidly frozen brains of PSP patients, Parkinson's disease (PD) patients, and controls. In PSP, we found glutamic acid markedly increased in the nucleus accumbens; taurine significantly increased in nucleus accumbens, substantia nigra, and globus pallidus; and gamma-aminobutyric acid significantly increased in nucleus accumbens and putamen. Glycerophosphoethanolamine contents were significantly increased in most regions. Glutathione, which is significantly decreased in substantia nigra in PD, was increased in this brain region in PSP, suggesting that different mechanisms may be responsible for destruction of dopaminergic nigrostriatal neurons in these two disorders.

Aged↗

Postural hypotension--cochleo-vestibular hypoxia--deafness.

The postural hypotension syndrome i.e. a sudden fall in blood pressure as a result of sudden rising, leading to severe vertigo and fainting has been known for a very long time, but the diagnostic criteria for hypotension has changed recently. Medical textbooks claim that unless systolic B.P. falls more than 20 mm upon rising it is not hypotension. A recent British investigation employing radio-active isotope tomography has shown that an orthostatic fall in B.P. of 10 mm in elderly persons may cause a 60% decrease in cerebral blood-flow lasting several minutes (2). It has been estimated that at least 30% of the patients in nursing-homes suffer from vertigo. Last year 6000 elderly persons in Denmark were treated for fracture of the femoral neck. This study points out that concurrent with vertigo and fainting the cochlea does suffer from decreased blood supply, and hearing subsequently deteriorates. The reason why this has not been recognized until now is that while vertigo comes and disappears within minutes and is distinctly felt by the patient, the hearing loss develops nearly as slowly as does hearing loss caused by moderate noise exposure over many years. Axelsson et al. in a recent study point out that at least TTS is influenced by cochlear blood flow (4).

Adult↗

4-phenylpyridine and three other analogues of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine lack dopaminergic nigrostriatal neurotoxicity in mice and marmosets.

C57 black mice were injected repeatedly with maximal tolerated doses of 2 chemical analogues of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP); 4-phenylpyridine and 4-phenyl-1,2,3,6-tetrahydropyridine. Although both compounds were clearly acutely toxic to mice, neither caused any reduction in striatal dopamine content after chronic exposure. Two MPTP analogues which may be formed endogenously during the metabolism of brain monoamines, 2-methyl-1,2,3,4-tetrahydroisoquinoline and 2-methyl-1,2,3,4-tetrahydro-beta-carboline, were injected repeatedly into common marmosets. Again, although both compounds appeared highly toxic, neither caused any reduction in striatal dopamine content. It appears unlikely that any of these 4 MPTP analogues causes idiopathic Parkinson's disease.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

Offspring control of cerebrospinal fluid GABA concentrations in lactating rats.

The concentrations of gamma-aminobutyric acid (GABA) and its metabolic precursors glutamate (Glu) and ornithine (Orn) were measured in cerebrospinal fluid (CSF) samples obtained from the cisterna magna of freely moving lactating rats on: postpartum day 5 when the rats were with their pups, day 6, 6 h after removal of the pups, and day 7, 24 h after mother-pup reunion. The concentration of GABA was non-detectable in the absence of pups (condition 2) but forty-fold above the limit of detection whenever the rats and the pups were together (conditions 1 and 3). Glu and Orn were low in but increased in and still more so in. Thus, the CSF concentration of GABA, an inhibitory neurotransmitter which profoundly influences behavior and hormone secretion is markedly increased by the pup-related stimuli, which control the behavior and the endocrine secretions of the lactating rat.

Animals↗

Exposure to cigarette smoke does not decrease the neurotoxicity of N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in mice.

Epidemiological surveys have repeatedly shown that idiopathic Parkinson's disease (PD) occurs less frequently in persons who have smoked cigarettes for many years than among age-matched non-smokers. Since PD might be caused by neurotoxins chemically similar to N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), we explored the possible protective effect of repeated exposure to cigarette smoke against MPTP neurotoxicity in the C57 black mouse. Mice given MPTP and exposed to cigarette smoke suffered just as great a depletion of striatal dopamine as did mice treated only with MPTP. We discovered also that different lots of C57 black mice obtained from a single supplier can have markedly different sensitivities to MPTP.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

Amino acids, glutathione, and glutathione transferase activity in the brains of patients with Alzheimer's disease.

We measured the contents of amino acids and related amino compounds in autopsied brain from 22 patients with Alzheimer's disease (AD) and in cortical biopsy specimens from 2 other patients. The diagnosis of AD was established neuropathologically in all 24 patients by the presence of both neurofibrillary tangles and neuritic plaques in neocortex. The mean contents of gamma-aminobutyric acid (GABA), and of the GABA dipeptide homocarnosine, were significantly reduced in frontal and occipital cortices and in hippocampus of the autopsied brains of AD patients compared to control patients without neurological disease. However, GABA contents were normal in frontal cortex in biopsy samples from 2 patients. Phosphoethanolamine contents were significantly reduced at autopsy in frontal and occipital cortex, and in the substantia innominata. We found no evidence of a deficiency of glutamate, aspartate, or taurine in AD brain, as has been claimed. Glutathione contents and glutathione transferase activities were normal in frontal cortex and substantia innominata. The mechanism of neuronal death in patients with AD is unlikely to involve either insufficient synthesis of glutathione or failure to conjugate free radicals with glutathione.

Adolescent↗

Inability to produce a model of dialysis encephalopathy in the rat by aluminum administration.

We attempted to produce a rat model of brain aluminum toxicity in order to explore whether or not aluminum accumulation produces the neurochemical changes observed in brains of patients who die with dialysis encephalopathy. Daily subcutaneous injection of Al(OH)3 caused marked elevation of serum aluminum concentrations, but did not increase brain aluminum contents, either in rats with normal renal function, or in rats with unilateral or 5/6 nephrectomies. LiCl pretreatment, which has been reported to cause irreversible renal failure, did not impair renal function nor aid in achieving elevated brain aluminum contents. No reductions in brain contents of gamma-aminobutyric acid (GABA) or in glutamic acid decarboxylase (GAD, E.C.4.1.1.15) and choline acetyltransferase (ChAT, E.C.2.3.1.6) activities were observed in aluminum-treated rats. We conclude that the rat is not a suitable laboratory animal to explore the role of aluminum toxicity in causing the GABA and ChAT deficits present in brains of hemodialyzed human patients.

Aluminum Hydroxide↗

Tissue culture evidence for a circulating neurotoxin in Huntington's chorea.

We explored with tissue culture techniques the possibility that a circulating neurotoxin might cause the premature loss of certain populations of neurons that characterizes Huntington's chorea (HC). Explants of striatum from newborn rats were grown in culture media containing 30% by volume of serum from drug-free HC patients or from healthy control subjects. Glutamic acid decarboxylase (GAD), the enzyme which synthesizes gamma-aminobutyric acid (GABA), was later assayed in these explants as an indicator of the health of GABAergic striatal neurons. The sera of 7 of 8 HC patients decreased GAD activity markedly when present as 30% of the tissue culture medium. When present in lower concentration (15%), HC sera either decreased or increased GAD activity in explants. Deproteinization of sera with perchloric acid did not abolish these effects on GAD activity. A depressant effect on GAD activity was detected in the cerebrospinal fluid of 1 of 4 HC patients tested. These experiments suggest the presence of a circulating neurotoxin, possibly excitotoxic to GABAergic striatal interneurons, and probably a small molecule. Identification of this substance could lead to an effective preventive treatment for persons genetically at risk for HC.

Adolescent↗

Alpha-tocopherol and beta-carotene do not protect marmosets against the dopaminergic neurotoxicity of N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine.

Idiopathic Parkinson's disease (PD) may possibly be caused by one or more unidentified neurotoxins present in the environment, or formed endogenously, which progressively damage dopaminergic nigrostriatal neurons. N-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is an experimental neurotoxin which produces biochemical and neuropathological changes in humans, lower primates and mice that closely resemble those found in PD. Because the mechanisms of neuronal damage in both idiopathic PD and in the MPTP model of PD may involve free radical formation in the substantia nigra, antioxidants might protect dopaminergic neurons. Previously, we found that both alpha-tocopherol and beta-carotene partially protected mice against MPTP. However, in the experiments described in this paper, neither alpha-tocopherol nor beta-carotene, each administered in massive doses, had any demonstrable protective effect for dopaminergic nigrostriatal neurons in marmosets injected with low doses of MPTP. Without more knowledge about the identity of the neurotoxin(s) causing idiopathic PD, and their mechanism of action, it is not possible at this time to predict whether these 2 antioxidants might be clinically useful in preventing or ameliorating PD.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

Olfactory mechanisms in the control of maternal aggression, appetite, and fearfulness: effects of lesions to olfactory receptors, mediodorsal thalamic nucleus, and insular prefrontal cortex.

During lactation the female rat is hyperphagic, aggressive toward adult conspecifics, and less fearful than usual. In the first experiment the importance of olfactory receptors was investigated by surgically removing the olfactory epithelium of the nasal cavity. Mother rats subjected to this treatment consumed significantly less food and weighed less than sham-operated females. Moreover, experimental subjects displayed a dramatic decrease in maternal aggression. Fear behavior (sound-elicited freezing), on the other hand, was not affected by the lesions. The mediodorsal thalamic nucleus and the prefrontal insular cortex form part of the central olfactory system. The second experiment assessed the involvement of this olfactory-related thalamocortical system and the behavioral profile of mother rats. It was found that whereas the thalamic and cortical lesions left food intake and fear behavior unaffected, they significantly decreased the frequency with which the mother would attack an intruder male placed into her home cage. The sense of smell appears, according to the present experiments, to play a crucial role in maternal aggression.

Aggression↗

Development of partial tolerance to the gastrointestinal effects of high doses of recombinant tumor necrosis factor-alpha in rodents.

Treatment of healthy rats and mice with a single intravenous injection of recombinant human tumor necrosis factor-alpha (rHuTNF-alpha) caused a dose-dependent gastrointestinal inflammation. Within 30 min gastric emptying was blocked and tissue edema occurred in the small and large intestine. In the cecum hemorrhage occurred after 4 h at doses greater than or equal to 250 micrograms/kg. The cecum exhibited an acute inflammatory response following rHuTNF-alpha treatment similar to that seen in tumor necrosis at the same dose. The vascular endothelium became swollen, increased numbers of neutrophils and other leukocytes attached to and penetrated the endothelium, and finally hemorrhage occurred. Treatment of rats with daily injections of rHuTNF-alpha (250 micrograms/kg per d) for 3 wk failed to produce cachexia. Within 24-48 h rats became resistant to the hemorrhagic effect of rHuTNF-alpha, however, the cytokine still caused a transitory block of gastric emptying after 10 d of treatment. Treatment at 5- or 10-d intervals produced results similar to the initial injection. These results suggest that maximum hemorrhagic response will occur when rHuTNF-alpha is administered at intervals of 5-10 d rather than daily.

Animals↗