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Biomedical subjects

L Becker

Publications and source records attributed to L Becker.

At least 91 records · Page 5Linked to original sources
PubMed1995

Immunocytochemical detection of androgen receptor in human temporal cortex characterization and application of polyclonal androgen receptor antibodies in frozen and paraffin-embedded tissues.

Immunocytochemical and biochemical studies have demonstrated the presence of androgen receptor protein in various regions of the rodent and non-human primate cortex. Localization of androgen receptor in the human brain has, however, not been studied as extensively, because of difficulties in obtaining suitable tissue samples. In the present study, we have localized androgen receptors in both frozen and paraffin-embedded temporal cortex from epileptic patients undergoing resection. Polyclonal antibodies were raised against fusion proteins containing fragments of the human androgen receptor protein. The antibodies were affinity-purified against the corresponding fusion protein. Immunoprecipitation and Western blotting using extracts from human cell lines demonstrated the specificity of the antibodies for the human androgen receptor and lack of cross-reactivity with other steroid hormone receptors. Immunocytochemistry was performed on frozen and paraffin sections of human temporal cortex and in paraffin-embedded benign hyperplastic prostates (BPH), as well as prostate and breast carcinomas, by the streptavidin-biotin-peroxidase method. Antigen-retrieval was performed in paraffin-embedded sections using microwave irradiation. Specific nuclear and cytoplasmic immunoreactivity for androgen receptor was detected in neurons, astrocytes, oligodendrocytes, and microglia cells of the temporal cortex. In contrast, only nuclear staining was observed in BPH, prostate and breast carcinomas. Immunoprecipitation of human temporal cortex lysate and subsequent Western blot analysis demonstrated the expression of a 98 kDa immunoreactive protein, slightly smaller than the reported molecular weight of the wild-type androgen receptor. These results provide further evidence for the expression of androgen receptor in the human temporal cortex. The use of these immunocytochemical techniques should enable the retrospective determination of possible changes in androgen receptor expression in a variety of archival paraffin-embedded tissues, including samples of the human central nervous system.

Adolescent↗
PubMed1995

Delayed myelopathy after trivial neck injury in a patient with a cervical neurenteric cyst.

BACKGROUND: Neurenteric cysts are rare spinal lesions of congenital origin. They usually present insidiously with a long history of local spinal pain, radiculopathy and myelopathy. We report a 14-year-old male with a high cervical neurenteric cyst who developed a progressive myelopathy after minor neck trauma. Full recovery followed a partial cyst excision and decompressive procedure. SIGNIFICANCE AND CONCLUSION: The possible pathogenic mechanisms for this unusual presentation include hemorrhage into the cyst, sudden mechanical compression from abnormal spinal movement of a chronically distorted and compressed spinal cord, or an increase in the size of the cyst secondary to accumulation of cyst fluid. In this case a small increase in the cyst size may have resulted in increased mechanical distortion and spinal cord dysfunction on a compressive and ischemic basis.

Adolescent↗
PubMed1995

Polyamines in human brain: regional distribution and influence of aging.

Although much evidence has implicated polyamines in brain development and function, little information is available on these substances in human brain. We examined the influence of regional distribution and aging on putrescine, spermidine, and spermine levels in autopsied human brain. In the adult brain, concentrations of spermidine were the highest, followed by spermine and putrescine. All three polyamines showed a distinct and uneven distribution profile among the 10 examined brain areas. Spermidine levels were especially high in white matter and thalamus (20 and 9.3 nmol/mg of protein, respectively), whereas spermine concentrations were highest in cerebellar cortex (3.4 nmol/mg of protein). High levels of putrescine were observed in cerebral cortices, putamen, and hippocampus (0.7-1.2 nmol/mg or protein), with lowest levels in cerebellum and thalamus (0.3-0.5 nmol/mg of protein). No statistically significant influence of aging (1 day to 103 years; n = 57) on either putrescine or spermine levels in occipital cortex was observed. In contrast, spermidine levels increased markedly from birth, reaching maximal levels at approximately 40 years of age (+228% increase in the mean 41-year-old group vs. 6-week-old group), which were maintained up to senescence. These observations in human brain thus differ from those reported in the rodent, in which levels of all three polyamines show a pronounced postnatal reduction. Our data support the notion that polyamines may have roles in both postnatal brain development and in mature brain function.

Adolescent↗
PubMed1995

Sequence analysis of the tumor necrosis factor gene in pediatric patients with autoimmunity.

Tumor necrosis factor-alpha (TNF) is a multifunctional protein hormone that contributes to host defense and perinatal immunologic development. Dysregulated TNF production, however, occurs during the pathogenesis of autoimmune diseases and may be inherent to their development. In animal models of autoimmunity, dysregulated TNF synthesis has resulted from mutations in TNF gene regulatory sequences, specifically those sequences involved in translational control of TNF gene expression. In this study, we have determined whether mutations in the TNF translational control sequences are present in pediatric patients with type I diabetes mellitus and connective tissue diseases. Blood samples were collected from 48 patients with connective tissue diseases, 32 patients with diabetes, and 29 controls. A 250-bp fragment of the translational control sequences present in the TNF 3'-untranslated region was amplified by the polymerase chain reaction, sequenced, and analyzed relative to the published TNF sequence. In this study, all patients and controls exhibited the normal sequence, with no insertions or deletions in the translational control motifs. We conclude that polymorphisms in the TNF 3'-untranslated region occur infrequently, if at all, in patients with diseases examined here.

Autoimmune Diseases↗
PubMed1995

Primitive neuroectodermal tumors of the cerebrum and cerebellum: absence of t(11;22) translocation by RT-PCR analysis.

Cytogenetic analysis of peripheral primitive neuroectodermal tumors (PNETs) has demonstrated a consistent primary chromosomal change characterized by a reciprocal translocation t(11;22)(q24:q12). In the central nervous system PNETs, most frequent of which are the cerebellar medulloblastomas, the most prevalent chromosomal abnormalities include deletions and unbalanced translocations. The recent cloning of the t(11;22) breakpoint has revealed the fusion of the human FLI-1 gene on chromosome 11q24 with a gene EWS on chromosome 22q12 and permitted detection of fusion transcripts. Molecular genetic analysis for the presence of EWS/FLI-1 fusion transcripts by the reverse transcriptase-polymerase chain reaction has recently been applied to peripheral PNETs. In the present study, we analyzed eight central PNETs by reverse transcriptase-polymerase chain reaction for EWS/FLI-1 fusion transcripts. The tumors included six PNETs of the cerebellum, one supratentorial PNET of the frontal lobe and one PNET of the pineal region. Polymerase chain reaction analysis in all eight cases failed to reveal a t(11;22) translocation indicating that this is not a cytogenetic abnormality of the central PNETs. Reverse transcriptase-polymerase chain reaction analysis of EWS/FLI-1 fusion transcripts provides a novel adjunctive tool in the differentiation of central versus peripheral PNET.

Adolescent↗
PubMed1995

Hypophysectomy-induced regression of female rat lacrimal glands: partial restoration and maintenance by dihydrotestosterone and prolactin.

PURPOSE: Previous studies have implicated androgens and one or more as yet unknown pituitary or pituitary-dependent factors in the regulation of certain lacrimal gland functions. Many observations suggest that prolactin (PRL) might well be one of these factors. This study was designed to determine the effect of hypophysectomy on biochemical markers of exorbital lacrimal gland secretory capacity and to determine the extent to which dihydrotestosterone (DHT) and prolactin reverse these changes. METHODS: Female rats were hypophysectomized and, 5 days later, were treated for 2 days with DHT (0.25 or 1 mg/kg), PRL (1 or 5 mg/kg), combinations of the low or high doses of DHT and PRL, or vehicle only. The animals were killed, and crude membrane fractions were isolated from their lacrimal glands. An untreated group served as control. RESULTS: Lacrimal glands atrophied rapidly after hypophysectomy, losing 40% of their total and membrane-associated protein and 50% of their total DNA within 5 days. Total Na+,K(+)-ATPase and acid phosphatase activities and beta-adrenergic receptor number were decreased by half, whereas alkaline phosphatase activity and muscarinic cholinergic receptor number were reduced by 25% to 30%. DHT treatment increased total DNA above control values; it partially restored the amount of protein in the gland, the Na+,K(+)-ATPase and acid phosphatase activities, and the beta-adrenergic receptor number; and it fully restored the alkaline phosphatase activity. Prolactin treatment partially restored the amount of protein in the gland and the Na+,K(+)-ATPase activity; it fully restored the alkaline phosphatase activity and cholinergic receptor number; but it had no effect on the acid phosphatase activity or the beta-adrenergic receptor number. The high dose of DHT reduced the increase in cholinergic receptor number elicited by PRL. The high dose of PRL reduced the increases of total Na+,K(+)-ATPase and acid phosphatase elicited by DHT. CONCLUSIONS: These findings suggest that DHT and PRL exert general trophic actions on the lacrimal gland and specifically on lacrimal Na+,K(+)-ATPase, acid phosphatase, and neurotransmitter receptors. They also suggest that excessive levels of either hormone may be deleterious to secretory function. Because sex hormone levels are prone to wide fluctuations in women, our results also suggest a plausible hypothesis to account for the greater incidence in women of lacrimal insufficiency.

Acid Phosphatase↗
PubMed1994

Fullerenes in the 1.85-billion-year-old Sudbury impact structure.

Fullerenes (C60 and C70) have been identified by laser desorption, laser desorption post-ionization, and high-resolution electron-impact mass spectrometry in shock-produced breccias (Onaping Formation) of the Sudbury impact structure in Ontario, Canada. The C60 isotope is present at a level of a few parts per million. The fullerenes were likely synthesized within the impact plume from the carbon contained in the bolide. The oxidation of the fullerenes during the 1.85 billion years of exposure was apparently prevented by the presence of sulfur in the form of sulfide-silicate complexes associated with the fullerenes.

Carbon↗
PubMed1994

Halothane decreases pontine acetylcholine release and increases EEG spindles.

This study tested the hypothesis that halothane anesthesia would cause decreased acetylcholine (ACh) release within the medial pontine reticular formation (mPRF). ACh was collected by microdialysis and measured by high pressure liquid chromatography during wakefulness and during halothane-induced anesthesia. The electroencephalogram (EEG) showed that spindles were a reliable indicator of anesthetic depth. There was a statistically significant disease in ACh release during halothane anesthesia compared with ACh release during wakefulness. Spindles always disappeared during noxious stimulation and during emergence from anesthesia when pontine ACh levels began to increase. These results are consistent with previous data concerning brain stem cholinergic influences on thalamocortical spindle generation, and suggest that similar mechanisms generate cortical spindles during natural sleep and halothane anesthesia.

Acetylcholine↗
PubMed1994

Standardizing glutaraldehyde use in a regional group of ten major medical centers.

The ICPs of 10 Southern California medical centers were able to coordinate efforts to standardize the use of glutaraldehyde for high-level disinfection. In implementing "APIC Guidelines for Selection and Use of Disinfectants," variations in practice similar to those recognized nationally were identified. Through coordinated efforts, the regional ICP group researched and developed a position paper to facilitate standardization of high-level disinfection practice.

Disinfection↗
PubMed1994

A randomized study of telephone contact following completion of radiotherapy.

The hypothesis tested was that routine contact by telephone might significantly improve the adequacy of support for patients during the potentially stressful period between completing radiotherapy and the first follow-up visit. The study was a randomized controlled trial in which 100 patients were allocated either to telephone contact (intervention arm) or usual care (control arm). Adequacy of support was assessed by a questionnaire administered at the first follow-up visit. There were no significant differences in the perceived adequacy of support between the two arms. Of the 72 patients who completed questionnaires, 76% of those in the intervention arm versus 61% in the control arm rated their support after radiotherapy as 'extremely adequate'. The 95% confidence interval (CI) for this 15% rate difference was -6- +36. Analysis by intention to treat showed a rate difference of only 4% (95% CI -17-(+)25) in favour of intervention. We conclude that, given the limited resources currently available, it is not possible to justify a policy of routine contact by telephone for all patients completing radiotherapy.

Adult↗
PubMed1994

Cytokine-induced expression of nitric oxide synthase in C2C12 skeletal muscle myocytes.

Nitric oxide (NO) is an important mediator of diverse physiological and pathological responses. To determine whether NO production can be induced in skeletal muscle, we stimulated C2C12 mouse skeletal muscle myocytes with putative inducers of nitric oxide synthase (NOS). Neither lipopolysaccharide (LPS), interleukin-1 alpha (IL-1), tumor necrosis factor-alpha (TNF), nor interferon-gamma (IFN) was able to stimulate nitrite production by C2C12 cells when administered alone. However, combinations of IFN with either TNF or IL-1 resulted in significant nitrite production; simultaneous stimulation of cells with all three cytokines resulted in significantly increased nitrite production compared with any combination of two cytokines. Northern analysis of RNA obtained from stimulated C2C12 cells revealed induction of a single mRNA band that precisely coincided with the mRNA band of mouse macrophage-inducible NOS (iNOS). Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis followed by sequencing of the 5' 765 bases of the skeletal muscle iNOS cDNA demonstrated exact homology with mouse macrophage iNOS. These findings indicate that combinations of cytokines stimulate NO production in skeletal muscle cells via induction of the macrophage-type iNOS gene.

Amino Acid Oxidoreductases↗
PubMed1993

S-adenosylmethionine decarboxylase in human brain. Regional distribution and influence of aging.

Recent experimental animal studies have implicated brain polyamines as having roles in both brain development and human brain neurodegenerative conditions. In order to provide baseline information, in normal human brain, on one of the key polyamine synthesising enzymes, S-adenosylmethionine decarboxylase (SAMDC), we examined the sensitivity of this enzyme to various cofactors/inhibitors, its regional distribution, and influence of aging in neurologically normal autopsied human brain. SAMDC in normal human brain is similar to that reported in other mammalian cells with regard to substrate affinity (Km = 39 microM), marked sensitivity to putrescine activation (+600%), inhibition (methylglyoxalbisguanidine and MDL 73811), and pH optimum (7.2). There was an uneven distribution of enzyme activity in human brain, and of the 12 brain regions examined, the highest activity was observed in occipital, parietal, frontal and temporal cortices (36-58 pmol/h/mg protein); intermediate activity in cerebellar and insular cortex, pulvinar thalamus, caudate and putamen (12-27 pmol/h/mg protein); and lowest activity in medial-dorsal thalamus, lateral globus pallidus and white matter (< 11 pmol/h/mg protein). The influence of aging (1 day to 103 years) on SAMDC activity in occipital cortex, the region showing the highest activity in human brain (n = 59) was also determined. Enzyme activity increased by approximately 600% from age 6 months to near maximal levels at age 10 years, then remained generally unchanged up to 103 years. Since SAMDC is a key regulatory enzyme in the synthesis of spermidine and spermine, the marked increase in SAMDC activity in the neonate and the sustained high enzyme levels throughout adulthood, imply a role for these polyamines in both development and mature brain function.

Adenosylmethionine Decarboxylase↗
PubMed1993

Female transgenic mice carrying multiple copies of the human gene for S100 beta are hyperactive.

Down syndrome (DS) (trisomy 21) is the most frequent genetic cause of mental retardation in man. The gene coding for the beta subunit of human S100 protein (S100 beta) has been mapped to chromosome 21. The dimeric form of S100 beta may function as a neurotrophic factor in the CNS and may also influence the establishment of hippocampal long-term potentiation (LTP). To study the behavioral consequences of overexpression of S100 beta in an animal model, we derived four lines of transgenic mice carrying multiple copies of the human S100 beta gene. The human S100 beta gene was expressed in the brain of these mice in a cell-specific and gene-dose-dependent manner. The motor and posture patterns of 16-month-old transgenic mice and their control (non-transgenic) littermates were studied in two tests, open field and bar-crossing, in order to examine novelty induced exploratory activities. Transgenic female mice were significantly hyperactive in both tests in comparison with their female control littermates. These differences were independent of the line of origin of the mice suggesting a causal relationship between the observed hyperactivity and the presence of multiple copies of the integrated human S100 beta gene. In contrast, transgenic males were not hyperactive in comparison with controls. Neither male nor female transgenic mice displayed any coordination defects. We speculate about how an interaction between the effects of elevated S100 beta levels and female specific hormonal changes could have resulted in the observed female restricted hyperactivity.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Optic glioma in children: surveillance, resection, or irradiation?

Eighty-seven consecutive children with newly diagnosed optic glioma were managed at University of Toronto hospitals 1958-1990. Overall the 10-year survival, relapse-free survival and freedom from second relapse rates were 84%, 68% and 85%. Twenty-seven patients relapsed or progressed, of whom 40% were free of a second relapse 10 years after the first relapse. Fourteen patients had a second relapse. Thirteen are dead. None survived 5 years after second relapse. Patients with anteriorly located tumors (N = 35), which involved the optic nerve, or chiasm and optic nerves, fared better than those with posteriorly located tumors (N = 52) with spread beyond the chiasm, 10-year survival 95% versus 76%, (p = .02), 10-year relapse-free survival 80% versus 59% (p = .02), respectively. For posterior tumors primary irradiation was more effective than primary subtotal resection for prevention of subsequent relapse, 10-year relapse-free survival 75% versus 41% (p = .02), but salvage therapy was, in part, successful and multivariate analysis of prognostic factors influencing survival for posterior tumors indicated that neither primary resection nor primary irradiation were significant factors. For first relapse, primary irradiation and the presence of neurofibromatosis were the significant favorable factors. Since 1977 and for posterior optic glioma subtotal resection or surveillance were used in 21/29 (72%) patients compared with 4/23 (17%) previously. Ten-year survival rates before and after 1977 were 78% and 67% and 10-year relapse-free survival 64% and 56%, respectively.

Adolescent↗