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Biomedical subjects

H Radner

Publications and source records attributed to H Radner.

At least 37 records · Page 2Linked to original sources
PubMed1998

Massive injury to the heart after attempted active compression-decompression cardiopulmonary resuscitation.

An 84-year-old woman was unsuccessfully resuscitated for 3 min using standard cardiopulmonary resuscitation (CPR), followed by 15 min of active compression-decompression (ACD). The autopsy revealed that death was due to myocardial infarction complicated by rupture of the infarcted area and pericardial tamponade was diagnosed. Furthermore, a series of rib fractures, a transverse fracture of the sternum, rupture of the pericardial sac, the right ventricle, both atria and lacerations of the ascending aorta, were found with no signs of a vital reaction. To our knowledge, such extensive cardiac injury after CPR has not been previously reported. It is suggested that the pre-existing pericardial tamponade, the age of the patient and the application of the ACD-device to incorrect areas of the chest contributed to the extent of the cardiac injury. This case further adds to the suspicion of an increased risk of cardiac injuries when using an ACD device for cardiac massage.

Aged↗
PubMed1998

Expression of blood group antigens A and/or B in diseased corneas.

PURPOSE: Only epithelial cells are thought to express blood group antigens (bga) A and/or B in normal corneas, and ABO blood group (bg) matching seems to reduce immune rejection in high risk transplantations. This study attempts for the first time to investigate to what extent the bga A and/or B are expressed in diseased corneas. METHODS: Thirty-nine diseased corneal buttons of 39 patients were examined. Immunohistochemical staining of paraffin-embedded sections was performed with monoclonal mouse anti human blood groups A and B antibodies using the Streptavidin-Biotin-peroxidase complex technique (LSAB Kit, Dako). RESULTS: The expression of blood group antigens A and/or B on the cornea was found to correlate directly with the blood group of the patients in all cases. The corneal epithelium of all 18 patients with blood groups A and/or B could be stained with antibodies to bga A and/or B. However, neither bga A nor bga B could be detected in any corneal cells of patients with the blood group O (21 patients). In addition to the epithelium, the stromal keratinocytes as well as the endothelium contained immunohistochemically detectable bga A and/or B in cases of keratitis or keratoconus, but not in stromal and/or endothelial cells of corneas with pseudophakic bullous keratopathy and Fuchs' dystrophy (all patients with the bgs A and/or B). CONCLUSION: These findings show that an up-regulation of bga A and/or B in corneal stromal and endothelial cells is possible in diseased corneas. This phenomenon might play an important role in graft rejection after corneal transplantation.

ABO Blood-Group System↗
PubMed1997

Lipoprotein lipase controls fatty acid entry into adipose tissue, but fat mass is preserved by endogenous synthesis in mice deficient in adipose tissue lipoprotein lipase.

Lipoprotein lipase (LPL) is the rate-limiting enzyme for the import of triglyceride-derived fatty acids by muscle, for utilization, and adipose tissue (AT), for storage. Relative ratios of LPL expression in these two tissues have therefore been suggested to determine body mass composition as well as play a role in the initiation and/or development of obesity. To test this, LPL knockout mice were mated to transgenics expressing LPL under the control of a muscle-specific promoter (MCK) to generate induced mutants with either relative (L2-MCK) or absolute AT LPL deficiency (L0-MCK). L0-MCK mice had normal weight gain and body mass composition. However, AT chemical composition indicated that LPL deficiency was compensated for by large increases in endogenous AT fatty acid synthesis. Histological analysis confirmed that such up-regulation of de novo fatty acid synthesis in L0-MCK mice could produce normal amounts of AT as early as 20 h after birth. To assess the role of AT LPL during times of profound weight gain, L0-MCK and L2-MCK genotypes were compared on the obese ob/ob background. ob/ob mice rendered deficient in AT LPL (L0-MCK-ob/ob) also demonstrated increased endogenous fatty acid synthesis but had diminished weight and fat mass. These findings reveal marked alterations in AT metabolism that occur during LPL deficiency and provide strong evidence for a role of AT LPL in one type of genetic obesity.

Adipose Tissue↗
PubMed1997

[Corneal Langerhans cells. Behavior during storage in organ culture].

BACKGROUND: Corneal HLA-DR antigens are going to be lost during organ culture storage. This study investigated if this phenomenon is based on down-regulation of the HLA-DR antigen, or on a loss of the HLA-DR-positive corneal Langerhans cells (LCs). MATERIAL AND METHODS: Corneal LCs were stained in situ by the method of fluorescence-associated immunohistochemistry, and the organ culture mediums underwent flow cytometric analysis for HLA-DR-positive corneal LC at the end of the storage period. RESULTS: All stored corneas were negative for HLA-DR after 14 days and HLA-DR antigens could be detected in culture medium at the end of the storage time. CONCLUSION: Flow cytometry showed that organ culture storage leads to loss of HLA-DR-positive cells and not only to a loss of antigen presentation.

Antigen Presentation↗
PubMed1996

Muscle-specific overexpression of lipoprotein lipase in transgenic mice results in increased alpha-tocopherol levels in skeletal muscle.

Lipoprotein lipase (LPL) has been implicated in the delivery of chylomicron-located alpha-tocopherol (alpha-TocH) to peripheral tissues. To investigate the role of LPL in the cellular uptake of alpha-TocH in peripheral tissue in vivo, three lines of transgenic mice [mouse creatine kinase- (MCK) L, MCK-M and MCK-H] expressing various amounts of human LPL were compared with regard to alpha-TocH levels in plasma, skeletal muscle, cardiac muscle, adipose tissue and brain. Depending on the copy number of the transgene, LPL activity was increased 3- to 27-fold in skeletal muscle and 1.3- to 3.7-fold in cardiac muscle. The intracellular levels of alpha-TocH in skeletal muscle were significantly increased in MCK-M and MCK-H animals and correlated highly with the tissue-specific LPL activity (r = 0.998). The highest levels were observed in MCK-H (21.4 nmol/g) followed by MCK-M (13.3 nmol/g) and MCK-L (8.2 nmol/g) animals when compared with control mice (7.3 nmol/g). Excellent correlation was also observed between intracellular alpha-TocH and non-esterified fatty acid (NEFA) levels (r = 0.998). Although LPL activities in cardiac muscle were also increased in the transgenic mouse lines, alpha-TocH concentrations in the heart remained unchanged. Similarly, alpha-TocH levels in plasma, adipose tissue and brain were unaffected by the tissue specific over-expression of LPL in muscle. The transgenic model presented in this report provides evidence that the uptake of alpha-TocH in muscle is directly dependent on the level of LPL expression in vivo. Increased intracellular alpha-TocH concentrations with increased triglyceride lipolysis and NEFA uptake might protect the myocyte from oxidative damage during increased beta-oxidation.

Adipose Tissue↗
PubMed1996

Microwave digestion methods for the determination of trace elements in brain and liver samples by inductively coupled plasma mass spectrometry.

Two microwave digestion systems (open-focused and closed-pressurized) were tested for the mineralization of human brain and bovine liver (NIST SRM 1577a) as dissolution steps prior to the determination of 16 trace elements (Bi, Cd, Co, Cs, Cu, Fe, Hg, Mn, Mo, Pb, Rb, Sb, Sn, Sr, Tl, and Zn) by inductively coupled plasma mass spectrometry (ICP-MS). Digestion parameters (mass of sample, digestion mixture, and power/time steps) were optimized using temperature and pressure sensors. Digestions with the open-focused microwave system require larger volumes of conc. HNO(3) and 30% H(2)O(2) than digestions with the closed-pressurized system. Both systems produce correct results for the bovine liver samples. The concentrations obtained for the digests of the open-focused system tend to be less precise than the concentrations from the "closed-pressurized" digests. Because the "open-focused" digests must be diluted to 50 mL to bring the acid concentration to 0.7-2.0 mol/L required by the ICP-MS (closed-pressurized digests need to be diluted to only 20 mL), the detection limits for the system with the open-focused digestion are higher than for the system with the closed-pressurized digestor. The open-focused digestor cannot handle more than 150 mg brain tissue, whereas the closed-pressurized system can mineralize 470 mg. The latter method gave better results with brain tissue than the open-focused system. The preparation of brain tissue as reference material for the determination of trace elements in brain samples is described.

Journal Article↗
PubMed1996

Magnetic resonance imaging and spectroscopy of progressive cerebral involvement in Kearns Sayre Syndrome.

Kearns Sayre Syndrome (KSS) belongs to the group of so called 'mitochondrial encephalopathies'. Magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) may have the potential to noninvasively detect and monitor disease specific cerebral involvement, as we wish to demonstrate in a patient whom we have followed for 3.5 years. At first presentation with incomplete external ophthalmoplegia, ptosis, pigmentary retinopathy and impaired hearing MRI demonstrated ill defined areas of symmetric T2-prolongation in the dorsal parts of the mesencephalon, the pons and in both cerebellar hemispheres. While the patients clinical symptoms deteriorated, including the onset of dysphagia, signal abnormalities spread downwards into the medulla oblongata involving the glossopharyngeal nuclei and supratentorially into the white matter. Proton MRS performed with the PRESS sequence (TR/TE 1500/136 ms) in the area of white matter damage showed a doublet at 1.33 ppm, which is characteristic for the presence of lactate. Our findings suggest MRI abnormalities to increase in parallel with neurologic progression of KSS and confirm the utility of 1H-MRS in supporting mitochondrial respiratory chain insufficiency as the underlying cause of parenchymal alterations.

Adult↗
PubMed1996

Na2B12H11SH (BSH) in combination with systemic hyaluronidase: a promising concept for boron neutron capture therapy for glioblastoma.

OBJECTIVE: In an attempt to optimize the therapeutic potential of Na2B12H11SH (BSH) for boron neutron capture therapy for glioblastoma, the present study investigates the influence of systemically applied hyaluronidase (a glycolytic enzyme that enhances the activity of chemotherapeutic agents in different types of cancer) on the biodistribution of BSH in patients with glioblastoma. METHODS: Patients in two uniform groups (Groups A and B, each of which had 10 patients with histologically confirmed glioblastomas) received BSH at a dose used in earlier therapeutic trials (75 mg/kg of body weight, administered intravenously) 24 hours before surgical debulkment. Patients from Group B received additional hyaluronidase (200,000 IU, administered intravenously) immediately before BSH infusion. Boron concentrations were analyzed by inductively coupled plasma-atomic emission spectroscopy. RESULTS: The application of hyaluronidase was associated with a statistically significant improvement in the tumor (maximum)-to-blood concentration ratio of 1.83 (range, 0.68-3.67) compared with 1.31 (range, 0.8-1.78) with BSH alone. Moreover, with the use of hyaluronidase, there was a tendency for a higher maximal concentration in tumor (not statistically significant). Boron accumulation in glioblastoma tissue was highly selective in both groups, with tumor-to-healthy brain concentration ratios ranging from 6:1 to 20:1. CONCLUSION: These preliminary data suggest that hyaluronidase improves BSH biodistribution and, consequently, the therapeutic potential of this boron carrier. This finding might be of clinical value in the future.

Adult↗
PubMed1995

Severe hypotension and coma secondary to unrecognized chronic anterior hypophysitis.

We report an endocrine emergency of a 52-year-old woman with chronic anterior-pituitary failure of autoimmune origin who developed hypopituitary crisis with coma and severe hypotension provoked by an intercurrent bronchopneumonia. At admission to the ICU hypopituitarism had not been diagnosed and only Hashimoto's thyroiditis with thyroid replacement therapy could be obtained from the patient's history. Although the patient presented with somatic signs suggestive of hypopituitarism, other causes of coma and hypotension had first to be excluded. In the absence of specific treatment the patient died 18 h later with refractory cardiac arrest. Diagnosis of acute decompensated chronic hypophyseal failure must be considered if hypothermia, refractory hypotension and signs of infection without fever are associated with a short stature and the loss of axillary and public hair. Waiting for laboratory confirmation of the diagnosis must not delay immediate life-saving specific glucocorticoid treatment.

Acute Disease↗
PubMed1995

Muscle-specific overexpression of lipoprotein lipase causes a severe myopathy characterized by proliferation of mitochondria and peroxisomes in transgenic mice.

In extrahepatic tissues lipoprotein lipase (LPL) hydrolyzes triglycerides thereby generating FFA for tissue uptake and metabolism. To study the effects of increased FFA uptake in muscle tissue, transgenic mouse lines were generated with a human LPL minigene driven by the promoter of the muscle creatine kinase gene. In these mice human LPL was expressed in skeletal muscle and cardiac muscle, but not in other tissues. In proportion to the level of LPL overexpression, decreased plasma triglyceride levels, elevated FFA uptake by muscle tissue, weight loss, and premature death were observed in three independent transgenic mouse lines. The animals developed a severe myopathy characterized by muscle fiber degeneration, fiber atrophy, glycogen storage, and extensive proliferation of mitochondria and peroxisomes. This degree of proliferation suggests that FFA play an important role in the biogenesis of these organelles. Our experiments indicate that LPL is rate limiting for the supply of muscle tissue with triglyceride-derived FFA. Improper regulation of muscle LPL can lead to major pathological changes and may be important in the pathogenesis of some human myopathies. Muscle-specific LPL transgenic mouse lines will serve as a useful animal model for the investigation of myopathies and the biogenesis of mitochondria and peroxisomes.

Animals↗
PubMed1995

Severe hypertriglyceridemia, reduced high density lipoprotein, and neonatal death in lipoprotein lipase knockout mice. Mild hypertriglyceridemia with impaired very low density lipoprotein clearance in heterozygotes.

Lipoprotein lipase (LPL)-deficient mice have been created by gene targeting in embryonic stem cells. At birth, homozygous knockout pups have threefold higher triglycerides and sevenfold higher VLDL cholesterol levels than controls. When permitted to suckle, LPL-deficient mice become pale, then cyanotic, and finally die at approximately 18 h of age. Before death, triglyceride levels are severely elevated (15,087 +/- 3,805 vs 188 +/- 71 mg/dl in controls). Capillaries in tissues of homozygous knockout mice are engorged with chylomicrons. This is especially significant in the lung where marginated chylomicrons prevent red cell contact with the endothelium, a phenomenon which is presumably the cause of cyanosis and death in these mice. Homozygous knockout mice also have diminished adipose tissue stores as well as decreased intracellular fat droplets. By crossbreeding with transgenic mice expressing human LPL driven by a muscle-specific promoter, mouse lines were generated that express LPL exclusively in muscle but not in any other tissue. This tissue-specific LPL expression rescued the LPL knockout mice and normalized their lipoprotein pattern. This supports the contention that hypertriglyceridemia caused the death of these mice and that LPL expression in a single tissue was sufficient for rescue. Heterozygous LPL knockout mice survive to adulthood and have mild hypertriglyceridemia, with 1.5-2-fold elevated triglyceride levels compared with controls in both the fed and fasted states on chow, Western-type, or 10% sucrose diets. In vivo turnover studies revealed that heterozygous knockout mice had impaired VLDL clearance (fractional catabolic rate) but no increase in transport rate. In summary, total LPL deficiency in the mouse prevents triglyceride removal from plasma, causing death in the neonatal period, and expression of LPL in a single tissue alleviates this problem. Furthermore, half-normal levels of LPL cause a decrease in VLDL fractional catabolic rate and mild hypertriglyceridemia, implying that partial LPL deficiency has physiological consequences.

Adipose Tissue↗
PubMed1994

Boron neutron capture therapy: boron biodistribution and pharmacokinetics of Na2B12H11SH in patients with glioblastoma.

Data on biodistribution and pharmacokinetics of Na2B12H11SH are few and lack in standardization. This study comprises a uniform series of 10 patients with glioblastoma administered Na2B12H11SH i.v. 24 h before surgery at a dose level used in earlier therapeutical trials (75 mg/kg body weight). Boron concentrations in tumor, normal brain, peritumoral edematous brain, blood, and urine were determined by inductively coupled plasma-atomic emission spectroscopy 24 h after Na2B12H11SH administration; boron uptake in tumor (mean, 12.2 micrograms/g) was sufficiently selective compared to concentrations in normal and edematous brain (1.2 and 2.3 micrograms/g, respectively). Mean concentration ratio of tumor:blood was slightly above unity. Boron concentration in blood decreased according to an open two-compartment model, mean excretion in urine over 24 h was 81.9%. The only side effect was an inconstant facial flush. Among efforts aiming at an optimized treatment protocol a dose escalation study seems to be justified.

Borohydrides↗
PubMed1994

Symmetric hypoplasia of the temporal cerebral lobes in an infant with glutaric aciduria type II (multiple acyl-coenzyme A dehydrogenase deficiency).

Symmetric hypoplasia of the temporal cerebral lobes was demonstrated by magnetic resonance imaging of the brain in a macrocephalic male patient with glutaric aciduria type II within the first week of life. Psychomotor development was normal until the age of 11 months, when the patient died of sudden cardiac arrest. Autopsy revealed symmetric hypoplasia of the temporal cerebral lobes with loss of axons and hypomyelination in the temporal medullary layers.

Fatal Outcome↗
PubMed1994

Subcellular boron-10 localization in glioblastoma for boron neutron capture therapy with Na2B12H11SH.

Because of the short range of the highly energetic particles helium-4 and lithium-7 that results from neutron-induced disintegration of boron-10, the efficacy of Boron Neutron Capture Therapy (BNCT) is heavily dependent on 10B-microlocation. Despite the crucial importance of boron-10, there is little specific information with regard to the agent currently used for inducing BNCT, namely Na2B12H11SH. In the present study, a subcellular 10B-location was investigated in tumor tissue obtained from seven patients with glioblastoma World Health Organization Grade IV. These patients received Na2B12H11SH at doses used in therapeutic trials (75 mg/kg body weight in five patients, and 150 mg/kg body weight in two patients, respectively). In three cases, boron-10 was identified in glioblastoma cells by laser microprobe mass analysis. In these tumors, boron-10 was found only in the nuclei of neoplastic cells but not in other cell compartments. These preliminary results suggest a predominant association of Na2B12H11SH with the nuclei of malignant glioma cells and thus support the value of Na2B12H11SH as a suitable boron carrier for BNCT.

Borohydrides↗
PubMed1993

Tumor induction by ras and myc oncogenes in fetal and neonatal brain: modulating effects of developmental stage and retroviral dose.

Introduction into fetal rat brain cells of a replication-defective retroviral vector harboring v-Ha-ras and v-gag-myc rapidly causes the induction of highly malignant undifferentiated neuroectodermal tumors following transplantation into the brains of syngeneic hosts [Wiestler, et al. (1992) Cancer Res. 52: 3760-3767]. In the present study, we have investigated the modulating effect of the developmental stage of neural target cells and of the dose of the retroviral vector used in the grafting experiments. Exposure of fetal cells from embryonic day (E)12 or E14 produced a 100% incidence of malignant neuroectodermal tumors which led to the death of recipient animals after a median latency period of 32 days. A 100-fold reduction of the virus dose from 2.062 x 10(6) to 2.062 x 10(4) focus-forming units/ml resulted in a lower tumor incidence of 25%. Of six neural grafts exposed to v-Ha-ras and v-myc at E16, only one showed evidence of tumorigenesis (low-grade astrocytoma and hemangioma). All other transplants were morphologically normal for observation periods of 26 weeks, indicating a marked loss of transforming activity of ras and myc in more advanced stages of brain development. In retrovirus-exposed donor cells which caused the development of neural tumors in recipient rats, malignant transformation was also evident during culture in vitro, usually after 9-12 days. Oncogene complementation was also studied in the newborn rat brain. After microinjection of the retroviral vector into the brain at postnatal day (P)0, P1 and P3, 5 out of 20 animals (25%) developed a total of seven brain tumors. Histopathologically, three of these neoplasms were malignant neuroectodermal tumors which, in contrast to those induced in fetal brain transplants showed evidence of focal glial and/or neuronal differentiation. In addition, we observed one oligodendroglioma, two hemangiomas and a malignant hemangioendothelioma. These data indicate that neural precursor cells and endothelia of the rat brain represent the major target cells for the complementary action of ras and myc and that the use of target cells from later developmental stages (E16 and postnatal) leads to the induction of both primitive and more differentiated neoplasms.

Animals↗
PubMed1993

Complementary tumor induction in neural grafts exposed to N-ethyl-N-nitrosourea and an activated myc gene.

Using a combination of transplacental carcinogen exposure and retrovirus-mediated oncogene transfer into fetal brain transplants, we have studied complementary transformation by N-ethyl-N-nitrosourea (NEU) and the v-myc oncogene in the nervous system. Previous experiments had demonstrated that both agents will not induce tumors independently whereas simultaneous expression of v-H-ras and v-gag/myc exerted a powerful transforming potential in neural grafts. In order to identify other genetic alterations that co-operate with an activated myc gene, the neurotropic carcinogen NEU was used to generate mutations of cellular genes. On embryonic day 14 (ED14), pregnant donor animals (F344 rats) received a single i.v. dose of NEU (50 mg/kg). Twenty-four hours later (ED15), the fetal brains were removed, triturated and incubated with a retroviral vector carrying the v-gag/myc oncogene. Subsequently, these primary cell suspensions were transplanted stereotactically into the caudate-putamen of syngenic adult recipients. After latency periods of 3-6 months, 5 of 10 recipients harboring ED15 fetal brain transplants developed malignant, poorly differentiated neuroectodermal tumors in the grafts. No tumor development was observed in seven recipients harboring ED16 neural grafts. Cell lines were established from three tumors and the 110 kd gag/myc fusion protein encoded by the retroviral construct was identified in the tumors by Western blotting. Several candidate genes for mutational activation by NEU including the H-ras, K-ras and neu oncogenes were analyzed for specific point mutations by polymerase chain reaction (PCR) and direct DNA sequencing of the PCR products. However, no mutations were found in any of these genes. These findings lend further support to the multistep hypothesis of neoplastic transformation in the brain. The tumors induced in this model provide an interesting tool for the identification of genes that co-operate with an activated myc gene in neurocarcinogenesis.

Animals↗
PubMed1993

Pathologic correlates of incidental MRI white matter signal hyperintensities.

We related the histopathologic changes associated with incidental white matter signal hyperintensities on MRIs from 11 elderly patients (age range, 52 to 82 years) to a descriptive classification for such abnormalities. Punctate, early confluent, and confluent white matter hyperintensities corresponded to increasing severity of ischemic tissue damage, ranging from mild perivascular alterations to large areas with variable loss of fibers, multiple small cavitations, and marked arteriolosclerosis. Microcystic infarcts and patchy rarefaction of myelin were also characteristic for irregular periventricular high signal intensity. Hyperintense periventricular caps and a smooth halo, however, were of nonischemic origin and constituted areas of demyelination associated with subependymal gliosis and discontinuity of the ependymal lining. Based on these findings, our classification appears to reflect both the different etiologies and severities of incidental MRI signal abnormalities, if it is modified to treat irregular periventricular and confluent deep white matter hyperintensities together.

Aged↗