Hemolytic crisis: the Dialysis Center of Lincoln experience.
Explore the source record for details and available documents.
Aged↗
Biomedical subjects
M Schwarz
Publications and source records attributed to M Schwarz.
Conserved biological function between Pax-2 and Pax-5 in midbrain and cerebellum development: evidence from targeted mutations.
The development of two major subdivisions of the vertebrate nervous system, the midbrain and the cerebellum, is controlled by signals emanating from a constriction in the neural primordium called the midbrain/hindbrain organizer (Joyner, A. L. (1996) Trends Genet. 12, 15-201). The closely related transcription factors Pax-2 and Pax-5 exhibit an overlapping expression pattern very early in the developing midbrain/hindbrain junction. Experiments carried out in fish (Krauss, S., Maden, M., Holder, N. & Wilson, S. W. (1992) Nature (London) 360, 87-89) with neutralizing antibodies against Pax-b, the orthologue of Pax-2 in mouse, placed this gene family in an regulatory cascade necessary for the development of the midbrain and the cerebellum. The targeted mutation of Pax-5 has been reported to have only slight effects in the development of structures derived from the isthmic constriction, whereas the Pax-2 null mutant mice show a background-dependent phenotype with varying penetrance. To test a possible redundant function between Pax-2 and Pax-5 we analyzed the brain phenotypes of mice expressing different dosages of both genes. Our results demonstrate a conserved biological function of both proteins in midbrain/hindbrain regionalization. Additionally, we show that one allele of Pax-2, but not Pax-5, is necessary and sufficient for midbrain and cerebellum development in C57BL/6 mice.
Animals↗
Delayed treatment with rolipram protects against neuronal damage following global ischemia in rats.
In this study the effect of post-treatment with rolipram, an inhibitor of cAMP phosphodiesterase, on neuronal damage following global ischemia was evaluated. Global cerebral ischemia was induced in male Wistar rats by four-vessel occlusion for 20 minutes. Rolipram was administered 6 hours after onset of ischemia and thereafter the following 7 days daily once at a dose of 0.3 or 3.0 mg/kg intraperitoneally. Four weeks after ischemia the amount of intact neurons in the hippocampus and in the striatum was assessed following perfusion fixation. The ischemia-induced neuronal damage in the CA1 sector of the hippocampus and in the striatum was reduced by rolipram at either dose. The present results show that treatment with rolipram reduces ischemic neuronal damage at a therapeutic window of 6 hours.
3',5'-Cyclic-AMP Phosphodiesterases↗
MRI study on delayed ancrod therapy of focal cerebral ischaemia in rats.
The therapeutic window for efficient post-treatment of focal cerebral ischaemia with the fibrinogen lowering agent ancrod was studied by magnetic resonance imaging (MRI) in spontaneously hypertensive rats (SHR). Ancrod or vehicle solution (0.9% NaCl) were i.v. infused (0.12 IU/kg per min) via implanted mini pumps starting 0.5, 1.5, 3 or 6 h after permanent proximal middle cerebral artery occlusion and lasting until brain mapping by multislice T2-weighted magnetic resonance imaging in vivo 24 h after middle cerebral artery occlusion. Plasma fibrinogen concentrations were measured before middle cerebral artery occlusion, before pump implantation and after magnetic resonance imaging. Total brain lesion volumes as determined by magnetic resonance imaging 24 h after middle cerebral artery occlusion were 131 +/- 36 (188 +/- 28)*, 151 +/- 39 (194 +/- 39)*, 147 +/- 44 (207 +/- 33)* and 209 +/- 60 (214 +/- 42) mm3 in rats with 0.5, 1.5, 3 and 6 h, respectively, delay of ancrod treatment (means +/- S.D., 8-11 animals/group, corresponding control groups in parentheses, *P < 0.05). Continuous i.v. ancrod infusions reduced plasma fibrinogen levels significantly (P < 0.05) in all ancrod-treated groups as compared to vehicle-treated controls until the end of the experiments 24 h after middle cerebral artery occlusion. In conclusion, significant cerebroprotection was achieved even when the onset of ancrod therapy for lowering of the plasma fibrinogen level was delayed for up to 3 h. To the best of our knowledge no drug efficacy has been reported so far with a therapeutic window of 3 h after permanent middle cerebral artery occlusion in spontaneously hypertensive rats suggesting that ancrod may provide an efficient therapy of acute human stroke.
Ancrod↗
Identification and characterization of a mouse oxysterol 7alpha-hydroxylase cDNA.
The synthesis of essential 7alpha-hydroxylated bile acids in the liver is mediated by two pathways that involve distinct 7alpha-hydroxylases. One pathway is initiated in the endoplasmic reticulum by cholesterol 7alpha-hydroxylase, a well studied cytochrome P450 enzyme. A second pathway is initiated by a less well defined oxysterol 7alpha-hydroxylase. Here, we show that a mouse hepatic oxysterol 7alpha-hydroxylase is encoded by Cyp7b1, a cytochrome P450 cDNA originally isolated from the hippocampus. Expression of a Cyp7b1 cDNA in cultured cells produces an enzyme with the same biochemical and pharmacological properties as those of the hepatic oxysterol 7alpha-hydroxylase. Cyp7b1 mRNA and protein are induced in the third week of life commensurate with an increase in hepatic oxysterol 7alpha-hydroxylase activity. In the adult mouse, dietary cholesterol or colestipol induce cholesterol 7alpha-hydroxylase mRNA levels but do not affect oxysterol 7alpha-hydroxylase enzyme activity, mRNA, or protein levels. Cholesterol 7alpha-hydroxylase mRNA is reduced to undetectable levels in response to bile acids, whereas expression of oxysterol 7alpha-hydroxylase is modestly decreased. The liver thus maintains the capacity to synthesize 7alpha-hydroxylated bile acids regardless of dietary composition, underscoring the central role of 7alpha-hydroxylated bile acids in lipid metabolism.
Animals↗
High incidence of spontaneous and chemically induced liver tumors in mice deficient for connexin32.
Connexins are subunits of gap junction channels, which mediate the direct transfer of ions, second messenger molecules and other metabolites between contacting cells. Gap junctions are thought to be involved in tissue homeostasis, embryonic development and the control of cell proliferation [1,2]. It has also been suggested that the loss of intercellular communication via gap junctions may contribute to multistage carcinogenesis [3-5]. We have previously shown that transgenic mice that lack connexin32 (Cx32), the major gap junction protein expressed in hepatocytes, express lower levels of a second hepatic gap junction protein, Cx26, suggesting that Cx32 has a stabilizing effect on Cx26 [6]. Here, we report that male and female one-year-old mice deficient for Cx32 had 25-fold more and 8-fold more spontaneous liver tumors than wild-type mice, respectively. Incorporation of bromodeoxyuridine (BrdU) into the liver was higher for Cx32-deficient mice than for wild-type mice, suggesting that their hepatocyte proliferation rate was higher. Furthermore, intraperitoneal injection, two weeks after birth, of the carcinogen diethylnitrosamine (DEN) led, after one year, both to more liver tumors in Cx32-deficient mice than in controls, and to accelerated tumor growth. Loss of Cx32 protein from hepatic gap junctions is therefore likely to cause enhanced clonal survival and expansion of mutated ('initiated') cells, which results in a higher susceptibility to hepatic tumors. Our results demonstrate that functional gap junctions inhibit the development of spontaneous and chemically induced tumors in mouse liver.
Animals↗
Retinal ischemia induced by the intraluminal suture method in rats.
In a model of transient focal cerebral ischemia in male Sprague-Dawley rats, which is induced by the intraluminal suture method, the acute effects on the electrical function of the retina were monitored by recording the electroretinogram. The electroretinogram was recorded from halothane-anesthetized rats before, during and after vascular occlusion through the intraluminal suture method for 180 min. During vascular occlusion the amplitude of the a- and b-wave were markedly suppressed. Upon reperfusion the a-wave recovered immediately. During reperfusion up to 48 h the amplitude of the b-wave increased to approximately 50% of the pre-occlusion value did not fully recover. Immunohistochemistry of the retinas revealed that the vascular occlusion induced the expression of glial fibrillary acidic protein in retinal Müller cells. The present data suggest that the intraluminal suture method leads to retinal ischemia.
Animals↗
Cyp7b, a novel brain cytochrome P450, catalyzes the synthesis of neurosteroids 7alpha-hydroxy dehydroepiandrosterone and 7alpha-hydroxy pregnenolone.
Steroids produced locally in brain (neurosteroids), including dehydroepiandrosterone (DHEA), influence cognition and behavior. We previously described a novel cytochrome P450, Cyp7b, strongly expressed in rat and mouse brain, particularly in hippocampus. Cyp7b is most similar to steroidogenic P450s and potentially could play a role in neurosteroid metabolism. To examine the catalytic activity of the enzyme mouse Cyp7b cDNA was introduced into a vaccinia virus vector. Extracts from cells infected with the recombinant showed NADPH-dependent conversion of DHEA (Km, 13.6 microM) and pregnenolone (Km, 4.0 microM) to slower migrating forms on thin layer chromatography. The expressed enzyme was less active against 25-hydroxycholesterol, 17beta-estradiol and 5alpha-androstane-3beta,17beta-diol, with low to undetectable activity against progesterone, corticosterone, and testosterone. On gas chromatography and mass spectrometry of the Cyp7b metabolite of DHEA the retention time and fragmentation patterns were identical to those obtained with authentic 7alpha-hydroxy DHEA. The reaction product also comigrated on thin layer chromatography with 7alpha-hydroxy DHEA but not with 7beta-hydroxy DHEA; when [7alpha-3H]pregnenolone was incubated with Cyp7b extracts the extent of release of radioactivity into the medium suggested that hydroxylation was preferentially at the 7alpha position. Brain extracts also efficiently liberated tritium from [7alpha-3H]pregnenolone and converted DHEA to a product with a chromatographic mobility indistinguishable from 7alpha-hydroxy DHEA. We conclude that Cyp7b is a 7alpha-hydroxylase participating in the synthesis, in brain, of neurosteroids 7alpha-hydroxy DHEA, and 7alpha-hydroxy pregnenolone.
17-alpha-Hydroxypregnenolone↗
Disturbances of precision grip in Huntington's disease.
Disturbed motor control of the fingers, as revealed by the response to unexpected loading of an object held in a precision grip, or to finger perturbation during isometric holding, has been studied in patients with Huntington's disease (HD) and in normal subjects. In normal subjects unexpected loading elicited a reflex response (mean latency 73 ms) in the first dorsal interosseus muscle (FDI). This was accompanied by a clear increase in grip force, reaching a maximum at 200 ms, which stabilised block position. Index finger perturbation led to a long-latency reflex response in the FDI of all normal subjects. No such response was seen in the HD patients. The response to object loading, in contrast, was present, but significantly delayed (mean onset 95 ms; P = 0.0135). The response was qualitatively normal, with grip force reaching a maximum at 220-230 ms. It is suggested that the absence of the long-latency stretch reflex and the delay in the response to loading in HD patients may represent a reduction in somatosensory input to the cortex caused by disruption of basal ganglia structures.
Adult↗
Flupirtine reduces functional deficits and neuronal damage after global ischemia in rats.
Global cerebral ischemia leads to selective neuronal damage in the CA1 sector of the hippocampus and in the dorsolateral striatum. In addition, it results in deficits in spatial learning and memory as shown by an increase in escape latency and swim distance during the escape trials and a reduction of time spent in the quadrant of the former platform position during the probe trial of the water maze. Flupirtine is a non-opioid, centrally acting analgesic which has been shown to be neuroprotective against N-methyl-D-aspartate (NMDA)-mediated toxicity in vitro. The purpose of the present study was to investigate the potential protective effect of flupirtine in vivo with both behavioural and histological measures of global cerebral ischemia. Global ischemia was induced by four-vessel-occlusion (4VO) for 20 min in rats. Flupirtine was administered at a dose of 5 mg/kg i.p. either 20 min before and 50 min after occlusion (pre-treatment) or directly and 70 min after occlusion (post-treatment). 1 week after surgery, spatial learning and memory was tested in the Morris water maze. Pre-treatment with flupirtine reduced the increase in escape latency and in swim distance induced by 4VO. It also diminished the deficit in spatial memory as revealed by an increase in time spent in the quadrant of the former platform position during the probe trial which was reduced by 4VO. Post-treatment with flupirtine had no effect on the deficits in spatial learning and memory induced by 4VO. Neuronal damage in the CA1 sector of the hippocampus and in the striatum produced by 4VO was significantly attenuated with pre-treatment of flupirtine whereas post-treatment did not affect this neuronal damage. The present data demonstrate that pre-treatment with flupirtine exerts a protective effect on hippocampal and striatal neuronal damage and on deficits in spatial learning induced by 4VO.
Aminopyridines↗
[Antibiotic use in necrotizing pancreatitis. Results of a controlled study].
BACKGROUND AND OBJECTIVE: The clinical course and death rate in acute necrotizing pancreatitis (ANP) are largely determined by septic complications as part of bacterial invasion of the necrotic tissues. It remains unclear whether antibiotic prophylaxis reduces bacterial invasion of the necroses or septic complications. It was, therefore, the aim of this study to evaluate the effect of prophylactic administration of antibiotics to patients with ANP. PATIENTS AND METHODS: In a prospective randomized study 13 patients with ANP and sterile necroses (quantified by contrast-enhanced computed tomography) were given twice daily 200 mg ofloxacin and twice daily 500 mg metronidazole intravenously. The results were compared to those in a control group of patients with ANP (n = 13) who had not initially received antibiotics. In both patient groups fine-needle biopsies of the necrotic areas were performed on days 1, 3, 5, 7 and 10. If there was evidence of infection, antibiotics were then also given to patients of the control group. RESULTS: The extent of the necroses was the same, 40%, in both groups. These necroses became infected in a median of 9.5 (treated group) and 10 days (untreated group). The clinical course, documented by the APACHE II score, showed significant improvement under antibiotic treatment (days 1-5-10: scores 15-13.0-9.5). In the (initially untreated) control group the clinical condition deteriorated significantly (days 1-5-10: score 11.5-15.0-16.0). The changes from days 1 to 5, 5 to 10 and 1 to 10 were highly significant (Wilcoxon test, P < 0.01). None of the patients in the antibiotic group died within the first 3 weeks, but 2 of the 13 in the control group died. CONCLUSION: Antibiotic prophylaxis neither prevented nor delayed bacterial infection of the necrotic pancreas. But it significantly improved the clinical course if started before the onset of infection of the pancreatic necroses.
Adult↗
SSCP analysis: a blind sensitivity trial.
Studies of the sensitivity of SSCP analysis usually have been performed under conditions contrary to the rules of quality control trials and have produced widely different results. We have performed a blind trial of the sensitivity of SSCP analysis for the detection of mutations in fragments up to 500 bp in length under a fixed single set of electrophoretic conditions. The mutation detection rate was 84%. In addition, we have identified a second mutation in nine samples. All these mutations are polymorphisms, including a novel polymorphism 1248 + 52T/C first reported in the present work.
Cystic Fibrosis Transmembrane Conductance Regulato↗
Comparative chromosomal study of five taxa of genus Callithrix, group jacchus (Platyrrhini, Primates).
The karyotypes of four marmoset species of the Callithrix jacchus group (C. aurita, C. kuhlii, C. geoffroyi, and C. penicillata) were investigated. The patterns of G-, C-, and NOR-bands of these karyotypes were compared with those of C. jacchus, previously described, in order to clarify the taxonomic relationships of this species group. All species present 2n = 46, 14 uni- and 30 biarmed autosomes, a median size submetacentric X chromosome, and the same NOR-band patterns. No rearrangement or constitutive heterochromatic variation differentiate these species, which differ only in the morphology of the Y chromosome. The data obtained indicate that, from the chromosomal point stand, the marmoset species of C. jacchus group constitute a homogeneous clade.
Animals↗
Chromosomal similarities and differences between tamarins, Leontopithecus and Saguinus (Platyrrhini, Primates).
The karyotypes of two taxa of genus Leontopithecus (rosalia and chrysomelas) are studied. Their G-, C- and NOR-banding patterns are compared with those of representatives of the genus Saguinus to determine chromosomal similarities and differences between the two genera and thus contribute to explaining phylogenetic relations between the tamarins. Leontopithecus, like the Saguinus, presents 2n = 46, 14 autosomes plus the Y acrocentric and 30 autosomes plus the X biarmed. No chromosomal rearrangement distinguishes the karyotypes of the representatives of genus Leontopithecus or genus Saguinus. The two genera are distinguished from each other by a paracentric inversion and pericentric inversions on at least four pairs of acrocentric autosomes, displacing the NORs of the small short arms in Leontopithecus to the proximal region of the long arms in Saguinus or vice versa. The tamarins are also distinguished by the distribution of noncentromeric constitutive heterochromatin. The data obtained indicate that the two tamarin genera are closely related chromosomally, suggesting that they probably originated from the same ancestral branch.
Animals↗
Effects of antioxidants on ischemic retinal dysfunction.
Transient occlusion of both common carotid arteries in normotensive rats leads to a reduction in the amplitude of the b-wave of the electroretinogram (ERG). The present study investigated whether the antioxidants vitamin E and lipoate attenuate the depression and enhance the recovery of the b-wave of the ERG in response to retinal ischemia. The ERG was recorded from halothane-anesthetized rats before. during and after transient (24 min) occlusion of both common carotid arteries. The substances were administered 20 minutes before or at the onset of ischemia. Both vitamin E (100 mg kg-1) and lipoate (100 mg kg-1) significantly reduced the depression of the b-wave during occlusion and accelerated recovery during reperfusion at either time point of application. The present results suggest that antioxidants provide protection against ischemic retinal dysfunction.
Animals↗
DNA Damage from Endogenous Processes, Workshop: 16-17 September 1996, German Cancer Research Centre Heidelberg, Germany.
Explore the source record for details and available documents.
DNA Adducts↗
Neuroleptic treatment increases soluble IL-2 receptors and decreases soluble IL-6 receptors in schizophrenia.
The cytokines interleukin-2 (IL-2) and interleukin-6 (IL-6) increase during immune activation, they are released from activated astrocytes and microglial cells in the central nervous system (CNS), and they are able to enhance the catecholaminergic neurotransmission. This study focused on the soluble receptors of IL-2 and IL-6 (sIL-2R, sIL-6R) as a part of the regulation system of IL-2 and IL-6. We studied serum levels of sIL-2R in 30 schizophrenic patients not under neuroleptic medication during an acute exacerbation of the disease and reexamined these patients under neuroleptic treatment after clinical improvement. The sIL-6R levels of 39 schizophrenic patients were estimated under the same conditions. The results were compared with the levels of sIL-2R and sIL-6R in 42 healthy controls. No difference was found between the schizophrenic patients before neuroleptic treatment and the healthy controls. During neuroleptic treatment, however, there was a significant increase of sIL-2R levels and a significant decrease of the sIL-6R levels between the pre- and post-conditions. In comparison with healthy controls, the treatment group also showed increased sIL-2R levels and decreased sIL-6R levels. These results suggest that treatment with neuroleptics is associated with increased sIL-2R and decreased sIL-6R. Since sIL-2R bind and inactivate IL-2, whereas sIL-6R form an active complex with IL-6, the increase of sIL-2R and the decrease of sIL-6R together may reflect a functional down regulation of these activating cytokines. This suggests that neuroleptic therapy has a differentiated immunomodulatory effect.
Adolescent↗
Cerebral haemorrhage in long-term survivors of childhood acute lymphoblastic leukaemia.
Modern treatment of childhood acute lymphoblastic leukaemia (ALL) has dramatically improved the prognosis for children with this disease. Therapeutic approaches consist of multimodal chemotherapy and radiotherapy with significant long-term side-effects. We report on 4 children out of a group of 120 newly diagnosed patients with ALL, who survived the disease for more than 2 years and developed a cerebral haemorrhage after chemotherapy and fractionated cranial irradiation. Following a period of 2-12 years the four children presented with acute neurological signs and symptoms. i.e. seizures, ataxia and hemiparesis. CT and MRI revealed intracerebral mass lesions, interpreted as haemorrhage. After neurosurgery the patients neurological state improved. Histological examination confirmed the suspected diagnosis of bleeding cavernous haemangioma or capillary telangiectases. There are two possibilities to explain these rare alterations: they may be pre-existent to the disease and therapy or they may be caused by irradiation. CONCLUSION Acute neurological symptoms in patients treated for ALL may be caused by spontaneous cerebral haemorrhaging of cavernous haemangiomas or capillary telangiectases induced by chemotherapy and/or radiotherapy.
Adolescent↗