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Biomedical subjects

S Hansen

Publications and source records attributed to S Hansen.

At least 199 records · Page 11Linked to original sources
PubMed1990

Immunohistochemistry of Pneumocystis carinii infection.

Pneumocystis carinii is the pre-eminent pulmonary pathogen and leading cause of death in patients with acquired immunodeficiency syndrome (AIDS). The diagnosis of this organism depends upon the morphologic demonstration of the cyst wall, trophozoite, or sporozoite in specimens from the lower respiratory tract. A variety of histochemical stains have been used to identify P. carinii, each with considerable limitations in specificity. Extrapulmonary spread and unusually destructive pulmonary patterns associated with P. carinii, although once considered rare, are seen occasionally in patients with AIDS. Traditional stains have proven to be less reliable in extrapulmonary sites. In 13 patients with AIDS, we stained formalin-fixed paraffin-embedded autopsy lung and other visceral organ sections using monoclonal antibody 3F6 (Dako, Santa Barbara, CA) to P. carinii. The antibody stained P. carinii in the lungs of seven patients with P. carinii pneumonia by Gomori methenamine silver stain (GMS). Numerous aggregates of P. carinii cysts were marked within alveoli, as is usually seen with other stains. No antibody staining was present in autopsy lung sections from non-AIDS patients with viral, fungal, or bacterial pneumonia. Clinically occult extrapulmonary P. carinii infection was seen in 4/7 (57%) patients with P. carinii pneumonia at autopsy. Monoclonal antibody to P. carinii stained organisms in all four (100%) patients with disseminated disease, as compared with 1/4 (25%) staining with GMS. Antibody staining of P. carinii was demonstrated in sections of thyroid, adrenal, and carinal lymph node (one patient), esophagus (one patient), kidney (one patient), and heart, thyroid, kidney, adrenal, liver, stomach, pancreas, spleen, and bone marrow (one patient).(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome↗
PubMed1990

Transfection of cytochrome P450 cDNAs into mammalian cells used in mutation and transformation assays.

The present work demonstrates that cDNAs coding for cytochrome P450 enzymes can be transfected into mammalian cells and expressed. In the present studies, two different cell systems were used for transfection: 10T1/2 cells which can be used to study initiation and promotion (Diamond, 1984) and AHH-1 cells which can be used to study mutation and clastogenesis (Crespi and Thilly, 1984, Crespi and Penman, 1989). Thus, a diversity of endpoints can be studied in cells which have increased metabolic capability. By increasing the metabolic capability of the target cell, the effects of nongenotoxic as well as genotoxic chemicals, can be examined in the appropriate in vitro systems. For example, the 10T1/2 cells can be treated with a nontransforming dose of an initiator followed by continuous treatment with a second chemical that requires cytochrome P450 specific metabolism to manifest its promoting activity. By this approach, greater insight into the role of chemical metabolism in the promotion process (and presumably other nongenotoxic effects) can be obtained. Additionally, the role of specific cytochrome P450s in the metabolism of different classes of carcinogens/drugs can be elucidated. A major advantage of having the metabolizing enzymes actually present in the target cell is that effects of chemicals can be studied in long-term, low-dose exposure protocols which will eliminate the acute toxic effects which are associated with many current protocols. Thus, more realistic environmental exposure conditions can be achieved by using these in vitro systems containing endogenous metabolism systems.

Animals↗
PubMed1989

High-resolution (1.5 A) crystal structure of phospholipase C from Bacillus cereus.

Both the phosphatidylinositol-hydrolysing and the phosphatidylcholine-hydrolysing phospholipases C have been implicated in the generation of second messengers in mammalian cells. The phosphatidylcholine-hydrolysing phospholipase C (PLC) from Bacillus cereus, a monomeric protein containing 245 amino-acid residues, is similar to some of the corresponding mammalian proteins. This, together with the fact that the bacterial enzyme can mimic the action of mammalian PLC in causing, for example, enhanced prostaglandin biosynthesis, suggests that B. cereus PLC can be used as a model for the hitherto poorly characterized mammalian PLCs. We report here the three-dimensional structure of B. cereus PLC at 1.5 A resolution. The enzyme is an all-helix protein belonging to a novel structural class and contains, at least in the crystalline state, three Zn2+ in the active site. We also present preliminary results from a study at 1.9 A resolution of the complex between PLC and inorganic phosphate (Pi) which indicate that the substrate binds directly to the metal ions.

Bacillus cereus↗
PubMed1989

Schizophrenia, tardive dyskinesia, and brain GABA.

We measured the contents of gamma-aminobutyric acid (GABA) and of other amino compounds in five regions of autopsied brain from 18 patients with schizophrenia and from a large group of adult control subjects dying without any neurological or psychiatric disorder. In addition, concentrations of GABA were measured in the cerebrospinal fluid (CSF) of living schizophrenic patients and control subjects. No deficiency of GABA was found in the frontal cortex, caudate nucleus, putamen, nucleus accumbens, or medial dorsal thalamus of patients dying with schizophrenia, nor were GABA concentrations low in the CSF of living schizophrenic patients. These results do not confirm our earlier report of low levels of GABA in the nucleus accumbens and thalamus of some schizophrenic patients. We do not find neurochemical evidence favoring an involvement of GABAergic neuronal hypofunction in the etiology either of schizophrenia or of neuroleptic-induced tardive dyskinesia.

Adult↗
PubMed1989

Translocation trisomy 21 in CVS not found in embryoblast: three different cell lines in CVS, amnion- and placental culture.

Chorionic villus samples from a healthy pregnant female were obtained for first-trimester prenatal diagnosis. A translocation trisomy 21 was diagnosed. A consecutive amniocentesis revealed a normal male karyotype. At term a healthy boy was born. Cytogenetic analysis from cord blood showed a regular karyotype of 46,XY, whereas in term placenta a pathological karyotype of 47,XY, +mar was found.

Adult↗
PubMed1989

An unusual aminoacidopathy associated with mitochondrial encephalomyopathy.

Five patients from two unrelated pedigrees are affected by an inherited form or forms of mitochondrial encephalomyopathy in which the exact site of the block in the respiratory chain has yet to be identified. All five patients regularly exhibit an unusual aminoacidopathy evident both in fasting plasma and in CSF. Alanine concentrations are elevated, reflecting high tissue pyruvate and lactate levels. Concentrations of the four essential amino acids threonine, methionine, tryptophan and lysine are substantially reduced, as are those of citrulline, ornithine and arginine. This pattern of amino-acid deficiency is apparently not due to failure to absorb the dibasic amino acids, to any abnormality of the urea cycle, to excessive synthesis and turnover of creatine, or to protein malnutrition. The aminoacidopathy presumably is a metabolic consequence of one or more impairments in the electron transport chain in mitochondria. A detailed explanation of its aetiology needs to be sought.

Adolescent↗
PubMed1989

Dominantly inherited olivopontocerebellar atrophy from eastern Cuba. Clinical, neuropathological, and biochemical findings.

A form of dominantly inherited olivopontocerebellar atrophy (OPCA) occurs commonly in persons of Spanish ancestry in northeastern Cuba. Its prevalence in the Province of Holguin is 41 per 100,000, a figure much higher than that found in western Cuba or in other parts of the world. The high prevalence is probably the result of a founder effect, but might be due to an interaction between a mutant gene and an unidentified environmental neurotoxin. We describe the clinical features of this disorder, and the neuropathological abnormalities in 7 autopsied patients. In addition, we report biochemical findings in plasma, cerebrospinal fluid (CSF) and urine obtained from 10 living OPCA patients. Quantitation of amino acids in fasting plasma showed a number of differences between the Cuban patients and healthy Canadian controls, but these are likely to have been caused by dietary differences. Amino acid concentrations in the CSF of the Cuban OPCA patients were similar to those of healthy Cuban controls, except for a decreased concentration of ethanolamine. Mean concentrations of dopamine metabolites were significantly low in the CSF of the OPCA patients, corresponding to neuronal depletion observed in the substantia nigra of autopsied cases. Examination of the patients' urines provided no evidence that either cyanide or 3-acetylpyridine is involved in causing this form of OPCA.

Adult↗
PubMed1989

Beta-N-methylamino-L-alanine. Chronic oral administration is not neurotoxic to mice.

Repeated dietary consumption of the neurotoxic amino acid beta-N-methylamino-L-alanine (BMAA), found in the seeds of Cycas circinalis, has been postulated as causing both amyotrophic lateral sclerosis (ALS) and the parkinsonism-dementia syndrome (PD) that were formerly very prevalent among the indigenous people of the Marianas Islands. Cynomolgus monkeys fed BMAA have been reported to develop behavioral and neuropathological changes like those found in human ALS. We gave large amounts of BMAA, totaling 15.5 g/kg of the L-isomer, by gavage to mice over 11 weeks without observing any behavioral abnormalities. When killed, these animals showed none of the neurochemical or neuropathological changes that would be expected in ALS or Parkinson's disease. Their striatal dopamine contents were normal, and there were no reductions in the contents of glutamate and aspartate in cerebral cortex like those encountered in sporadic human ALS. The results of this experiment do not support chronic ingestion of BMAA as the causative factor for Guamanian ALS or PD.

Administration, Oral↗
PubMed1989

Sutured retropupillary posterior chamber intraocular lenses for exchange or secondary implantation. The 12th annual Binkhorst lecture, 1988.

The histopathologic findings of four eyes obtained postmortem with iris-sutured posterior chamber intraocular lenses (PC IOLs) are described. These IOLs were implanted as exchange procedures. In most instances, the loops were not situated in the ciliary sulcus but rather were suspended behind the iris and ciliary body. Therefore, the primary mechanism of fixation of iris-sutured PC IOLs appears to be the sutures themselves rather than adherence to the ciliary tissues. This report of four eyes is preliminary, but the pathologic analysis, showing few significant lesions attributable to the IOL, provides a reason for optimism for using this technique. A long-term clinical study comparing the results of sutured PC IOLs with those of anterior chamber IOLs (AC IOLs) used in secondary or exchange implantation, as well as collection and analysis of more pathologic specimens, should provide a more definitive answer as to the preferred procedure.

Aged↗
PubMed1989

Behavior of mother rats in conflict tests sensitive to antianxiety agents.

Previous studies of freezing and open-field activity have demonstrated that lactating rats are less fearful or less anxious than nonpregnant ones. The purpose of this investigation was to observe the behavior of mother rats in conflict tests, which are frequently used in studies on the neurobiology of anxiety. In the punished drinking test, in which licking from a water spout is punished by electric shocks, mothers (observed on Day 1 postpartum following 24 hr of water deprivation) were found to drink more than virgins. Mothers (Day 1 postpartum) also consumed more food than controls in an unfamiliar open field. In contrast, no difference between mothers (Day 5 postpartum) and virgins was present in the exploration of an electrified shock probe. The largest maternal anticonflict effects in the drinking and feeding tests were recorded when the females were tested with their pups. Increased punished drinking was also observed in virgin rats treated with the anxiolytic benzodiazepine midazolam. Water-deprived virgins and mothers did not differ in the shock titration test, a result suggesting that diminished pain reactivity was unlikely to account for the increased punished drinking in mothers. Moreover, females in late pregnancy, which are hypoalgesic (Gintzler, 1980), did not lick more than virgins in the punished drinking test. Following 24 hr of water deprivation, unpunished drinking was higher in lactating females than in virgins, so the increased acceptance of punishment by mothers might have been due to their being more thirsty than virgins.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Medial hypothalamic involvement in maternal aggression of rats.

Extensive electrolytic lesions of the medial hypothalamus, or more restricted ones in its ventral division, decreased maternal aggression in rats operated upon on postpartum Days 2 and 3 and tested with female intruders 4 days later. Maternal aggression was attenuated also in mothers receiving intrahypothalamic infusions with ibotenic acid or parasagittal knife cuts along the lateral border of the ventromedial hypothalamic nucleus; in addition, the females with ibotenate lesions or knife cuts showed impaired lordosis behavior. None of the hypothalamic interventions were associated with deficits in pup retrieval. Lactation was impaired in groups with hypothalamic electrocoagulations but not in mothers with ibotenate lesions or knife cuts. The results suggest that the ventromedial hypothalamus and its lateral connections participate in control of maternal aggression.

Aggression↗
PubMed1989

Plasma concentrations of cholecystokinin, CCK-8, and CCK-33, 39 in rats, determined by a method based on enzyme digestion of gastrin before HPLC and RIA detection of CCK.

A new specific method for determination of cholecystokinin, CCK-8, and CCK-33, 39 in rat plasma is described. Plasma CCK radioimmunoassay (RIA) is difficult, because of cross-reactivity with gastrin. In the rat, problems because of difficulties in separating gastrin from CCK by high performance liquid chromatography (HPLC) exist. These were solved by enzyme digestion of gastrin before HPLC separation of molecular variants of CCK from gastrin fragments. Cholecystokinin immunoreactive forms in the HPLC fractions were determined by an antibody, which recognises the carboxyl terminus of CCK and gastrin. Fasting concentrations of small (CCK-8) and large (CCK-33, 39) molecular forms of CCK averaged 1.9 (0.3) pM and were raised to 13.4 (3.8) pM in rats fed ad libitum. Cholecystokinin in lactating rats rose two-fold after suckling, compared with 2.8 fold in response to feeding. The basal ratio between CCK-8 and CCK-33, 39 was approximately 1:1, but increased in favour of CCK-8 after feeding and in response to suckling. Gastrin like immunoreactivity measured in unextracted plasma was found to rise after feeding, but was unchanged in response to suckling.

Animals↗
PubMed1989

Cerebral cortical potentials to pure non-painful temperature stimulation: an objective technique for the assessment of small fibre pathway in man.

In six healthy subjects cortical potentials were evoked by rapidly changing heating or cooling stimuli to the hand. Recordings were made from the contralateral scalp area overlying the sensori-motor cortex, referred to a frontal reference. The potential averaged from 25 stimuli comprised a large positive wave with a mean amplitude of 9.2, SD 1.1 microV for heat and 8.8 SD 1.2 micro V for cold stimulation. The heat evoked potentials had longer peak latencies (range: 280-350 ms) than those elicited by cold stimuli (range: 178-200 ms). A lower amplitude positive wave of a longer latency was also recorded to both modes of stimulation over the corresponding ipsilateral cortex. Cortical thermal evoked potentials were absent in two patients, one with severe selective small fibre neuropathy and the other with syringomyelia, both of whom had high thermal thresholds demonstrated by the technique of Jamal et al. Cerebral potentials evoked by thermal stimuli may represent an alternative approach to the investigation of the central projections of the human small fibre system with both clinical and research potential.

Adult↗
PubMed1989

Post-viral fatigue syndrome: evidence for underlying organic disturbance in the muscle fibre.

Ten patients with post-viral fatigue syndrome and abnormal serological, virological, immunological and histological studies were examined by the single-fibre electromyographic (EMG) technique after excluding concurrent problems in the neuromuscular system. No abnormality of fibre density was noted but all patients had abnormal jitter values. Very high jitter values were not associated with impulse or concomitant blocking. The findings confirm the organic nature of the disease. A muscle membrane disorder probably arising from defective myogenic enzymes is the likely mechanism for the fatigue and the single-fibre EMG abnormalities. This muscle membrane defect may be due to the effects of a persistent viral infection.

Adolescent↗
PubMed1989

On the design of urokinase-labile prodrugs II. Structure-activity relationships in the urokinase catalyzed hydrolysis of H-GluGlyArg-anilides and -benzylamide.

Six H-GluGlyArg-anilides with different ortho or para substituents in the aniline group, and H-GluGlyArg-benzylamide were synthesized. KM and kcat for the urokinase-catalyzed hydrolysis of the compounds were determined at 37 degrees C and pH 7.40. In the initial rate measurements, HPLC was used for product quantitation. KM varied between 0.20 mM and 8.9 mM, whereas kcat varied between 0.8s-1 and 16.5s-1 for the investigated substrates. A Hammett plot and a "Charton plot" of the rate data are presented. kcat were, to a minor extent, dependent on the pKa of the leaving group, whereas steric effects had a more marked influence on the overall rate constant. A o-benzyl substituent in the aniline-leaving group exerts less sterical hindrance to the enzymatic hydrolysis than expected from the Charton plot. The significance of the results in relation to the development of urokinase labile dextran prodrugs in discussed.

Drug Design↗
PubMed1988

Tetrahydroisoquinoline lacks dopaminergic nigrostriatal neurotoxicity in mice.

1,2,3,4-Tetrahydroisoquinoline (TIQ) has been reported to occur in human brain, with its content being 10-fold higher in the brain of a patient with Parkinson's disease (PD) than in that of a control subject. This congener of the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) could be formed in brain by the condensation of phenylethylamine with metabolically formed formaldehyde. Phenylethylamine contents are greatly increased in the tissues of untreated patients with phenylketonuria. We injected C57 black mice repeatedly with maximal tolerated doses of TIQ, but later found no reduction in the contents of dopamine and its metabolites in their striata. We doubt that TIQ is a cause of PD, especially since the disorder has not been reported to occur in elderly patients with phenylketonuria.

Animals↗
PubMed1988

Retinal is not formed in vitro by enzymatic central cleavage of beta-carotene.

Rat intestinal mucosa was prepared and incubated with beta-carotene by the procedure of Goodman and Olson [Goodman, DeW. S., & Olson, J.A. (1969) Methods Enzymol. 15, 462-475] to determine beta-carotene cleavage activity. A new detection system for the reaction products of the described enzyme beta-carotene 15,15'-dioxygenase (EC 1.13.11.21) employs solvent extraction of retinoids and carotenoids followed by high-performance liquid chromatography separation and photometric detection of the pigments. It has not detected any newly formed retinal or other retinoids in the intestinal protein preparations from normal or vitamin A deficient rats. The latter were chosen as a possible source of more active enzyme preparations. With corresponding blank samples subjected to identical conditions of incubation but without added protein, small amounts of beta-apocarotenals could be detected. They were previously reported as cleavage products of beta-carotene [Ganguly, J., & Sastry, P.S. (1985) World Rev. Nutr. Diet. 45, 198-220] but are clearly not formed as a result of an enzymatic reaction. The failure to detect in vitro enzymatic central or random cleavage of the beta-carotene molecule in extracts of rat intestinal mucosa emphasizes the need to reevaluate the existing theory of conversion of beta-carotene into vitamin A.

Animals↗