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Biomedical subjects

P Kozlowski

Publications and source records attributed to P Kozlowski.

At least 19 recordsLinked to original sources

Chronic cerebrovascular insufficiency induces dementia-like deficits in aged rats.

Young and aged rats were subjected to cerebrovascular insufficiency (CVI) for 3 and 9 weeks. At the end of each time period, local cerebral blood flow (lCBF), spatial memory function, 31P- and 1H-NMR spectroscopy and imaging of the brains were evaluated in vivo. Morphometric counts of CA1 hippocampal neuron damage and staining for glial fibrillary acidic protein (GFAP) were done post-mortem. Results show that after 3 weeks of CVI, cortical and hippocampal lCBF was significantly reduced in young and aged animals respectively. In addition, young and aged rats at 3 weeks following CVI showed spatial memory deficits in the Morris water maze and elevation of 31P-phosphomonoester as measured by non-invasive NMR spectroscopy. At the same time period, in vivo 1H-microimaging (MRI) of brains showed areas of high signal intensity (suggesting local edema) localized asymmetrically to the right hippocampal region in young and aged CVI rats. Morphometry of the hippocampal CA1 sector at post-mortem confirmed the in vivo MRI changes and demonstrated that a significant percentage of the CA1 pyramidal cells were damaged after CVI. Nine weeks after CVI, hippocampal CBF reductions, spatial memory impairment, spectroscopic-microimaging changes and CA1 sector cell damage continued to be observed in the aged animals but were resolved in the young rat brains. In addition, GFAP immunoreaction progressively increased in the hippocampus of aged rats subjected to CVI for 9 weeks. It is concluded that cognitive, metabolic and morphologic damage was significantly more severe and longer lasting in aged than young rat brain after chronic CVI. The deficits observed in this rat model appear to mimic the early pathology reported in Alzheimer's disease and suggest that the present model could provide fundamental clues relative to the etiology and possible management of this dementia.

Aging

Shielded gradient coils and radio frequency probes for high-resolution imaging of rat brains.

A shielded gradient system and radio frequency probes for a 4.7-T/30-cm horizontal bore magnet are described. The systems were designed principally to obtain images and localized spectra from rat brains. The gradients can operate in either a shielded or non-shielded mode. The rf probe, which combines both highest sensitivity and highest resolution, consists of a large modified saddle type transmitter and a small surface reception coil, actively decoupled using diodes. The system performance is demonstrated on phantoms and on a rat brain, where an image with in plane resolution of 80 microns and a slice thickness of 150 microns is obtained.

Animals

Forebrain ischemia in diabetic and nondiabetic BB rats studied with 31P magnetic resonance spectroscopy.

In spontaneously diabetic BB rats, the effect of chronically maintained blood glucose levels on the degree of energy failure and brain pH change during an ischemic insult, and on subsequent recovery after reperfusion, was studied with in vivo 31P magnetic resonance spectroscopy. Short duration forebrain ischemia (10-min carotid occlusion plus hypotension of 50 mmHg) was induced in diabetic and nondiabetic male BB rats whose blood glucose levels were maintained with insulin. Spectra were obtained in 1-min blocks before, during, and for 1 h after ischemia. Before ischemia, hypoglycemic (blood glucose less than 3 mM) diabetic rats had an increased Pi peak intensity, with no significant pH change, compared with other groups. During ischemia, the rate and extent of hydrolysis of high-energy phosphate metabolites (as measured by an increase in Pi) decreased, and the severity of tissue acidosis increased as preischemia blood glucose concentration increased. Among hyperglycemic BB rats, similar ischemia-induced changes were found for subgroups with blood glucose levels of 13.7 +/- 1.2 and 20.3 +/- 0.6 mM, in keeping with the known decrease in hexose binding sites associated with chronic hyperglycemia. Decline in PCr level during ischemia was not significantly different between groups. With reperfusion, both Pi and pH values rapidly returned to preischemia values. PCr levels, however, did not recover in hyperglycemic diabetic animals, with the degree of residual impairment dependent on the preischemia glucose level. Results suggest that optimal management of diabetes may lessen the degree of injury within the ischemic penumbra in diabetic patients who suffer a stroke.

Analysis of Variance

Magnetic resonance imaging and 31P magnetic resonance spectroscopy study of the effect of temperature on ischemic brain injury.

Transient forebrain ischemia was induced in rats whose brain temperature was 31, 33, 35, 38, or 40 degrees C. The development of regional injury was followed using magnetic resonance (MR) imaging, with the ultimate extent of neuronal injury quantified histopathologically. Animals in the hypothermic groups showed minimal changes in MR images over 4 days; normothermic animals showed intensity enhancement attributed to progressive edema developing in the striatum and, later, in the hippocampus. Ischemia at 40 degrees C resulted in widespread edema formation by 1 day post-ischemia; animals in this group did not survive beyond 30 hours. Histopathological analysis at 4 days (1 day for the hyperthermic group) post-ischemia showed that neuronal damage in the normothermic group was confined to the hippocampus and striatum. Minimal damage was found in the hypothermic groups; damage in the hyperthermic group was severe throughout the forebrain. There were no differences in the pre-ischemia 31P MR spectra for the different groups. During ischemia, the increase in intensity of the Pi peak and the fall in tissue pH increased with temperature in the order hypothermic less than normothermic less than hyperthermic group of animals. Post-ischemia energy recovery was similar in all groups, while pH recovered more rapidly in hypothermic animals.

Animals

Hexagonal surface gradient coil for localized MRS of the heart.

A surface gradient coil designed to obtain localized magnetic resonance spectroscopy of the heart in vivo is described. Images and 31P spectra from phantoms and both pig and dog hearts in vivo are shown. The coil was used in conjunction with a rf surface coil to obtain 31P spectra from transmural sections of the left ventricular wall of a dog heart in vivo to demonstrate differences between normal and ischemic tissue.

Animals

[Experience with hysteroscopy or ultrasound-controlled removal of an intrauterine spiral with no visible thread in early pregnancy].

In case of intrauterine pregnancy with an intrauterine device (IUD), it is recommended, to remove the device because of the risk of abortions or septic complications. If the thread of the IUD is not visible, which often occurs because of growth of the uterus in pregnancy, it is advisable, to perform extraction by hysteroscopy or ultrasonic guidance. We report on 13 cases with hysteroscopic or ultrasonic guided IUD extraction in early pregnancy. 11 resulted in healthy infants, two pregnancies are continuing without complications.

Female

Induction by transforming growth factor beta of pemphigus vulgaris antigen activity in mouse papilloma cells.

Induction of a marker of epidermal spinous cells, pemphigus antigen activity, was detected by indirect immunofluorescence in murine papilloma cells exposed to human transforming growth factor beta (TGF-beta). Detection of pemphigus antigen activity required exposure of cells to 1.4 mM Ca2+ for 3 h just prior to immunoassay. The brief exposure to Ca2+ may be necessary for translocation of intracellular pemphigus antigen to the cell surface, where it is accessible to antibody. Cells grown in medium containing 0.02-0.04 mM Ca2+ were shown previously to be primarily basal cells characterized by pemphigoid antigen activity. Following treatment with 0.25-25 pg/ml TGF-beta for 44 h under 0.02-0.04 mM Ca2+ conditions, 63 +/- 9% (SD) of cells were pemphigus positive. This percentage was comparable to that of positive control cultures exposed to 1.4 mM Ca2+ for 44 h (70 +/- 10%) and was up to 2-fold that of solvent control cultures. Pemphigus antigen activity was significantly induced by 0.1-25 pg/ml TGF-beta, out of a tested range of 10(-5)-10(3) pg/ml. The total number of papilloma cell colonies was unaffected by treatment with 0.1-25 pg/ml TGF-beta but was reduced greater than 90% by treatment with 10(3)-5 x 10(3) pg/ml TGF-beta. The described immunofluorescence assay for pemphigus antigen activity may be useful for preliminary evaluation of differentiation-inducing agents in anticarcinoma therapy.

Animals

Selective, delayed increase in transfer constants for cerebrovascular permeation of blood-borne 3H-sucrose following forebrain ischaemia in the rat.

Experiments were conducted to explore the time course of changes in blood-brain barrier (BBB) permeability that may occur in the 2-vessel occlusion model of stroke in the rat. Anaesthetized Sprague-Dawley rats underwent 10 min of cerebral ischaemia produced by bilateral carotid occlusion plus haemorrhagic hypotension. After 6 min, or 3, 6, 18, 24, 48 h recovery and re-anaesthetization, an i.v. injection of 3H-sucrose was permitted to circulate for 30 min. Regional transfer constants (Ki) for BBB permeation of sucrose were calculated from the ratio of sucrose concentration in parenchyma relative to the time-integrated plasma concentration. In the 6-min group, all cerebral regions showed evidence of early BBB leakiness (increase in Ki above non-stroke baseline) which was maximal in forebrain cortex. This effect was diminished at subsequent time points, except in striatum and hippocampus which exhibited delayed intensification of opening, maximal in the 6 h group. Ki values had largely normalized by 24 h. Ki values were also determined 6 min, 6 h and 24 h after a 20-min stroke procedure. Early and regionally selective, delayed BBB openings were also seen, but recovery was not evident in cerebral regions at 24 h. Cortex exhibited a large increase in Ki indicating that a delayed, marked deterioration of BBB integrity had developed between the 6 h and 24 h time points. It is concluded that the combination of transfer constant measurements and the 2-vessel occlusion model could provide a sensitive means for investigating the cerebrovascular consequences and therapy of stroke.

Animals

Pemphigoid, pemphigus and desmoplakin as antigenic markers of differentiation in normal and tumorigenic mouse keratinocyte lines.

The expression of differentiation stages in a murine epidermal cell transformation model has been investigated as a basis for studies of chemically-induced differentiation. Antibodies in sera of patients with the autoimmune diseases bullous pemphigoid and pemphigus vulgaris exhibit specific reactivity to antigenic determinants of basal and spinous cells, respectively, in sections of mouse and human epidermis. In addition, spinous cells in epidermis are reactive with a mouse monoclonal antibody to desmoplakin, a desmosomal component immunologically distinct from pemphigus. These antibodies were used to identify and attempt to quantify keratinocyte subpopulations in culture based on differentiation stage. Epidermal cell lines were cultured under conditions which favour proliferation (0.02 to 0.04 mM extracellular Ca2+, i.e. low Ca2+ conditions) or differentiation (0.1 mM to 1.4 mM Ca2+), as previously shown using primary cultures of mouse keratinocytes. Two independently-derived normal keratinocyte lines demonstrated Ca2(+)-dependent reactivity with pemphigoid and pemphigus antiserum, like that which has been observed in primary cultures. Furthermore, a Ca2+ and time-dependent reactivity with the three antisera was also observed in a papilloma cell line (derived from one of the normal cell lines after treatment in vitro with 7,12-dimethylbenz[alpha]anthracene). Papilloma cells cultured under conditions of low extracellular Ca2+ were comprised of three subpopulations: cells reactive only with pemphigoid anti-serum, cells reactive only with desmoplakin antibody. However, like the normal cell lines, papilloma cells underwent a transition to predominantly a spinous cell population (i.e. reactive with pemphigus and desmoplakin antibody) in response to extracellular Ca2+. A slower loss of pemphigoid antibody reactivity was noted in papilloma cells, consistent with an abnormal regulation of differentiation. The attempt to characterize these dynamic transitions from basal to spinous cell subpopulations in culture was considered to be prerequisite for the use of the model to investigate differentiation-inducing agents in carcinoma therapy.

Animals

[Changes in the diagnosis and therapy of extrauterine pregnancy with special emphasis on ultrasound. Study at the Gynecologic Clinic of the Düsseldorf University, 1962-1983].

The diagnosis and therapy of ectopic pregnancy underwent a change with the introduction of ultrasound and the sensitive beta-hCG test. The modified management of ectopic pregnancy at the Department of Gynaecology of the University of Düsseldorf was analysed by examining the case history of 938 patients with suspected ectopic pregnancy from 1962-1983. The diagnosis ectopic pregnancy was confirmed for 348 patients (37%), whereas it was excluded in 590 cases (63%). The Pregnosticon test and the Gonavislide test yielded positive results in only little more than half of the cases with ectopic pregnancy. The Neo-Pregnosticon test was positive for 13 out of 15 patients. There was no ectopic pregnancy with a negative beta-hCG test (n = 31). Out of 261 patients examined by ultrasound, an ectopic pregnancy was proved directly four times. Sonographic pointers to an ectopic pregnancy were found with equal frequency in patients with confirmed ectopic pregnancy and in patients with excluded ectopic pregnancy (79%). In 17% of the patients with confirmed ectopic pregnancy this could not be detected by ultrasound. Out of 92 patients who had an ultrasound examination and a beta-hCG test, an intrauterine pregnancy could be excluded in spite of a positive pregnancy test in 94% of the ectopic pregnancies (n = 31) and in 31% of the cases with excluded ectopic pregnancy (n = 61). The incidence rate of ruptured tubule pregnancy was 44% before the introduction of ultrasound in 1973; it dropped subsequently to 37%. Since the introduction of the beta-hCG test in 1981 the incidence dropped further to 21%.(ABSTRACT TRUNCATED AT 250 WORDS)

Diagnosis, Differential

Cerebellar atrophy diagnosed by computed tomography and clinical data.

The diagnostic relevance of computed tomography (CT) in the classification of cerebellar atrophy or degeneration is unclear. Twenty-one patients with cerebellar atrophy at CT were studied and the findings were correlated to clinical data. Based upon such data the material was divided into two groups. In the first group (12 patients), with signs of cerebellar deficiency, 6 cases presented familial hereditary ataxia, and olivopontocerebellar atrophy of the Menzl type, 3 ataxia telangiectasia (Louis-Bar syndrome), 2 olivopontocerebellar atrophy of the sporadic type, and 1 adrenoleukodystrophy. In the second group (9 patients), without cerebellar deficit, cerebellar atrophy was found only occasionally. In all of them, there was cerebral atrophy. Clinically manifest cerebellar deficiency and cerebellar atrophy as evident at CT was mainly found in patients with familial genetic disorders. Cerebellar and/or vermian atrophy without clinical signs of cerebellar deficiency were observed only occasionally and were not specific.

Adolescent

The value of ovarian and placental steroid determinations in abnormal early pregnancy.

Concentrations of estradiol (E2), progesterone (P), and 170H-progesterone (170H-P) were measured by radioimmunoassay in serum samples obtained from a group of 98 women with threatened (n = 60), incomplete (n = 22) or missed (n = 16) abortion between the 4th and 17th week of pregnancy. The diagnosis was based on the clinical symptoms and the results of ultrasound scanning. In threatened abortion 54, out of 60 E2 values were within the 95% normal range, including most of the cases in which abortion occurred later. In incomplete abortion 18 of 21 E2 values were below the lower 95% confidence limit. In missed abortion, 11 of 15 E2 values were abnormal, being below the 95% normal range. Similar patterns in women with threatened, incomplete or missed abortion can be observed for values of P and 170H-P. Our results indicate that serum determinations of ovarian and placental steroids in women with early pregnancy failure are not of great clinical value.

17-alpha-Hydroxyprogesterone