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Biomedical subjects

C Nolan

Publications and source records attributed to C Nolan.

At least 37 records · Page 2Linked to original sources

Expression of multiple neuregulin transcripts in postnatal rat brains.

The distribution of neuregulin transcripts in rat brains was studied by both RNA blotting and in situ hybridization. Our data demonstrate that multiple neuregulin transcripts are expressed in neurons of the basal forebrain, the hippocampus, the diencephalon, the cerebellum, the brainstem, and the spinal cord. Developmental changes in the distribution of neuregulin transcripts were observed only in the cerebellum and the hippocampus. The intense neuregulin hybridization signals in the brainstem motor and sensory nuclei and the spinal motor neurons are suggestive of a functional involvement of neuregulins in motor and sensory systems. The expression of neuregulins in other parts of the brain also indicates that these factors are involved in a variety of central nervous system functions.

Animals↗

Meeting report of the EC/US workshop on genetic risk assessment: "human genetic risks from exposure to chemicals, focusing on the feasibility of a parallelogram approach".

This workshop was the concept of Professor Frits Sobels who passed away on the 6th of July 1993. The underlying idea of the Sobels' parallelogram approach is that an estimate (corrected by DNA-adduct dosimetry) of the genetic damage in human germ cells can be obtained by measuring a common endpoint in human and mouse somatic cells (such as gene mutation in lymphocytes) and in germ cells of mice, the desired target tissue inaccessible in humans. The main objective of the workshop was to identify the methodology, data requirements and mechanistic research to understand the human health impact of germ-cell mutagens. 4 chemicals were selected for review at the meeting: ethylene oxide, 1,3-butadiene, acrylamide and cyclophosphamide. The first 3 are important industrial chemicals with substantial use worldwide and, therefore, considerable potential human exposure. The 4th, cyclophosphamide, is a commonly used cancer chemotherapeutic agent. This first EC/US workshop on risk assessment was highly focused on the feasibility of the parallelogram concept to estimate potential germ-cell effects in humans. It represented an evaluation of current knowledge and the identification of future research needs for a more precise assessment of human genetic risks from exposure to mutagenic chemicals.

Animals↗

Six years of clinical experience using postcoital contraception in college women.

Postcoital contraception (PCC), also known as the "morning-after pill," has been used at the University of Rochester Health Service for several years. In 1985, the healthcare providers developed a formal protocol for dispensing PCC to female students presenting with the complaint of unprotected intercourse within the previous 72 hours. Patients are screened for any absolute contraindications to using birth control pills, are asked to sign a consent form, and are told to schedule a follow-up visit to evaluate pregnancy status and contraceptive options. Data from 1985 to 1991 is presented and include total number of times PCC was dispensed, side effects of medication, patient profiles, and predicted and actual pregnancy rates. The authors compare the data from the University of Rochester with data described in the literature and discuss recommendations for practice.

Adult↗

Why do Asian-born women have a higher incidence of gestational diabetes? An analysis of racial differences in body habitus, lipid metabolism and the serum insulin response to an oral glucose load.

We have observed a higher incidence of gestational diabetes (GDM) in Asian-born than in Caucasian women. Body habitus, serum lipid levels and the serum insulin response to a glucose load in pregnancy were compared in 15 women with normal glucose tolerance, 16 Caucasian women with GDM and 19 Asian-born women with GDM. Caucasian women with GDM, unlike Asian-born women with GDM, were obese compared with control women as measured by body mass index (p = 0.022). Both groups of GDM women had similar patterns of insulin response to oral glucose with a delayed insulin peak and an elevated 2-hour insulin level (p = 0.0021). In addition, the insulin response per unit of glycaemic stimulus (incremental insulin area/incremental glucose area at 1 hour) was reduced in both GDM groups (p = 0.035). Fasting serum triglyceride levels were higher in women with GDM although this was only significant in the Caucasian group (p = 0.014). Asian-born women with GDM had significantly lower (p = 0.041) serum cholesterol levels than Caucasian women with GDM. There was a significant correlation (p = 0.025) between glucose tolerance (area under the curve) and fasting serum triglyceride values. The relationship between lipid and carbohydrate metabolism in Asian-born and Caucasian women in pregnancy requires further investigation.

Adult↗

Nontuberculous mycobacterial disease in adult cystic fibrosis patients.

This study was conducted to determine the prevalence of mycobacterial disease in an adult cystic fibrosis (CF) population and to determine if there were any patients at higher risk for this disease within the group. Sixty-four patients (28 women, 36 men), ranging in age from 17 to 50 years were screened. One-step purified protein derivative skin testing with controls was performed and sputum was taken for examination. Eight of 64 had positive sputum culture for nontuberculous Mycobacterium. The CF patients with positive mycobacterial sputum cultures tended to be older and to have lower clinical scores than those who did not have Mycobacterium organisms in sputum. Guidelines to determine whether mycobacterial disease or colonization is present should be pursued for the CF population.

Adolescent↗

Tuberculosis and the surgeon.

With the resurgence of active tuberculosis in the United States, surgeons may be called upon to participate in the management of primary tuberculosis as well as major complications of the disease. To define the role of surgery in the diagnosis and treatment of tuberculosis in the 1990s, a 5-year retrospective review of 121 tuberculosis patients requiring invasive procedures in the course of their work-up was performed. Mycobacterium tuberculosis was cultured in 68% of patients, and atypical mycobacteria in 19%. Tissue was required to achieve the definitive diagnosis in 36%. Of the 93 patients with pulmonary evidence of tuberculosis, 54% presented with a pulmonary complication, 19 of whom required operative intervention. Extrapulmonary tuberculosis affected 45% of patients, including nine with miliary tuberculosis. Patients testing seropositive for human immunodeficiency virus accounted for 11% of the patients seen, emphasizing that the re-emergence of tuberculosis is not confined to the immunosuppressed.

Adolescent↗

A comparison of the acute toxicity, neuropathology, and electrophysiology of N,N-diethyl-m-toluamide and N,N-dimethyl-2,2-diphenylacetamide in rats.

The insect repellent DEET and the structurally related herbicide diphenamid both cause ataxia associated with a spongiform myelinopathy largely confined to the cerebellar roof nuclei. This local myelinopathy was accompanied by the formation of neuronal cytoplasmic clefts and was produced by a single dose of 1 to 3 g/kg N,N-diethyl-m-toluamide (DEET). These dose levels also produced a severe and often fatal prostration and clear electrophysiological signs of prolonged suppressed seizure activity. Diphenamid produced an identical myelinopathy after doses of 0.8 to 1.5 g/kg but without the severe prostration, suppressed seizures, or neuronal clefts. The effects of diphenamid were shown to be reversible over 3 to 7 days by neuropathological, motor, and auditory evoked response indices. Both compounds caused characteristic changes in auditory evoked response which may be useful in clinical diagnosis. Six other alkyl amides, two of which produce signs of CNS excitation, failed to produce myelinopathy at the maximum tolerated doses. Our findings show close parallels with a number of human cases of DEET poisoning and indicate that other amides, like diphenamid, also pose a potential hazard.

Aging↗

Estrogen and progesterone receptors in the normal female breast.

We have studied estrogen receptor (ER) and progesterone receptor (PR) in normal breast by immunocytochemistry using tissue biopsies and fine needle aspirates (FNA) and, in the case of ER, by enzyme immunoassay. For ER we found a high degree of reproducibility for biopsies taken from the upper outer quadrant: FNA, r = 0.56 (P less than 0.002); tissue section immunocytochemistry, r = 0.89 (P less than 0.0001); and enzyme immunoassay, r = 0.76 (P less than 0.0001). For PR, FNA (r = 0.56, P less than 0.002) and tissue section (r = 0.97, P less than 0.0001) were also found to be reproducible techniques. Using enzyme immunoassay, we were able to measure ER accurately in normal breast tissue. In 59 samples we found a range of 0-37 fmol/mg cytosol protein (mean, 4 fmol/mg). In an age-matched group of 126 women with breast cancer, we found a significantly higher ER [range, 0-139 fmol/mg; mean, 37 fmol/mg (P less than 0.001)]. We then analyzed the ER and PR content of FNAs obtained from the upper outer quadrant of the normal breast in 143 normal women. We found that in only 23 of 143 samples (16%) were greater than or equal to 50% epithelial cells stained. There was a relationship between ER and PR (P = 0.03) and a higher ER content in European women than in non-European women (P less than 0.03). The PR content was related to high body mass index (P less than 0.02) and family history of breast cancer (P = 0.04). Samples tended to be more frequently ER positive by FNA if taken in the follicular phase of the menstrual cycle. We conclude that, although the levels of ER and PR are low in normal breast, they can be accurately measured. There is significant variation of ER and PR with several clinical parameters.

Adolescent↗

Autoantibodies to glycoprotein antigens mediate subacute demyelinating encephalomyelitis in the Lewis rat.

Serum autoantibodies were induced in Lewis rats by immunization with a mixture of lentil lectin-binding glycoproteins isolated from bovine brain myelin. Intraperitoneal administration of 2-10 million syngeneic myelin basic protein-activated spleen cells to these rats led within 4-5 days to paralysis which, in most cases, persisted for several weeks. The major neuropathological features of the disease were numerous macrophages in both brain and spinal cord and large areas of demyelination, generally with axon preservation, particularly adjacent to the pial surfaces of the cord. This model is easily induced and will be useful for studies of demyelination and remyelination.

Animals↗

Anatomical mapping of glucose transporter protein and pyruvate dehydrogenase in rat brain: an immunogold study.

The regional and cellular distributions of glucose transporter protein (GT) and pyruvate dehydrogenase (PDH) have been studied with an enhanced immunogold method. The results showed significant amounts of GT in neuropil within regions known to exhibit high demands for glucose whilst neuronal perikarya showed little immunostaining. In contrast PDH immunostaining was most intense in neuronal perikarya. The distributions of these proteins were compared and discussed in relation to existing data on local cerebral glucose utilization and the distribution of other important metabolic enzymes. The results suggest that glucose is transported and metabolised in neuropil and that metabolic products such as pyruvate are transported into the neuronal cell body to undergo further metabolism.

Animals↗

Diagnostic usefulness of mycobacterial skin test antigens in childhood lymphadenitis.

Nontuberculous mycobacterial (NTM) infections are a frequent cause of chronic lymphadenitis in children. Previous studies of NTM antigen skin testing were inconclusive as a result of problems with study design and antigen formulation. The present study was undertaken with the Centers for Disease Control to determine whether newly formulated NTM skin test antigens applied in a double blind manner with a standard purified protein derivative could accurately distinguish NTM infections from those caused by Mycobacterium tuberculosis. Among the 11 children enrolled at our institution the NTM antigens correctly identified the 5 children with culture-proved NTM infections, as well as 2 other children with clinical or histopathologic data consistent with NTM lymphadenitis (P = 0.003, Fisher test). None of the 11 children cross-reacted with the Centers for Disease Control-supplied purified protein derivative. The NTM antigens appear to be useful in the diagnostic evaluation of lymphadenitis and perhaps in the evaluation of children with positive purified protein derivative skin tests.

Adolescent↗

Identification of the plasma membrane proteolipid protein as a constituent of brain coated vesicles and synaptic plasma membrane.

We have analyzed brain coated vesicles and synaptic plasma membrane for the presence of the plasma membrane proteolipid protein. Coated vesicles were isolated from calf brain gray matter with a final purification on Sephacryl S-1000 and reisolated twice by chromatography to ensure homogeneity. Fractions were analyzed by gel electrophoresis, immunoblotting for clathrin heavy chain, and by electron microscopy. Using an immunoblotting assay we were able to demonstrate the presence of the plasma membrane proteolipid protein in these coated vesicles at a significant level (i.e., approximately 1% of the bilayer protein of these vesicles). Reisolation of coated vesicles did not diminish the concentration of the protein in this fraction. Removal of the clathrin coat proteins or exposure of the coated vesicles to 0.1 M Na2CO3 showed that the plasma membrane proteolipid protein is not removed during uncoating and lysis but is intrinsic to the membrane bilayer of these vesicles. These studies demonstrate that plasma membrane proteolipid protein represents a significant amount of the bilayer protein of coated vesicles, suggesting that these vesicles may be a transport vehicle for the intracellular movement of the plasma membrane proteolipid protein. Isolation of synaptic plasma membranes proteolipid adult rat brain and estimation of the plasma membrane proteolipid protein content using the immunoblotting method confirmed earlier studies that show this protein is present in this membrane fraction at high levels as well (approximately 1-2%). The level of this protein in the synaptic plasma membrane suggests that the synaptic plasma membrane is one major site to which these vesicles may be targeted or from which the protein is being retrieved.

Animals↗

Purification of T47D human progesterone receptor and immunochemical characterization with monoclonal antibodies.

In order to obtain steroid-independent probes for human progesterone receptor (PR), the A [88-93 kilodalton (kDa)] and B (109-119 kDa) forms of PR from T47D human breast cancer cells were partially purified and used to generate a series of 14 monoclonal antibodies. Initially, unoccupied PR was isolated from cytosol extracts by steroid affinity chromatography, followed by chromatography on diethylaminoethyl Bio-Gel. The partially pure (3-15%) PR consisted of two steroid-binding components that migrated at 89 kDa and 109 kDa in reducing sodium dodecyl sulfate gels after being photoaffinity labeled with the synthetic progestin [3H]R5020. Two unique monoclonal antibodies to PR were derived from a male Lewis rat immunized with this material. One of these antibodies (JU601) was coupled to Sepharose 4B and used to purify T47D nuclear PR for additional immunizations. Highly purified (30-70%) PR migrated as 93 kDa and 119 kDa progestin-binding proteins in sodium dodecyl sulfate gels. In all, thirteen monoclonal antibodies were obtained that recognized epitopes shared by both receptor forms. One mouse immunoglobulin G (KC146) was completely specific for the larger B form. Interestingly, the epitope for this antibody was present on all PRs tested, including the B form of PR from chicken oviduct, whereas nine other antibodies recognized only human PR and the remaining four cross reacted with rabbit PR. With the exception of the JU145 and JU601 rat immunoglobulin Ms, all antibodies appeared to be completely specific for the A or B forms of PR. Each recognized the cytosol and nuclear forms of occupied as well as unoccupied PR. Although the relationship between B and A was not established, it is clear that an amino-terminal region of B is not present in A, and that a significant portion of A and B are either identical or very similar in amino acid sequence.

Antibodies, Monoclonal↗

Mouse hybrid sterility and testicular function.

Crosses of BALB/c female mice and inbred wild male mice (PWD, PWK) produce fertile female progeny, but the male offspring are sterile. The hybrid male sterility is a direct action of the hybrid sterility genes Hst-1s and Hstws. Previous reports concluded that spermatogenic arrest effected the sterility. However, the testicular steroidogenesis of hybrid sterile male mice has not been elucidated. In the present report, the steroidogenic capacity of hybrid sterile and parental strain males was directly assessed by quantifying testosterone secretion by maximally stimulated testes perfused in vitro. Additionally, Leydig cell mass and germ cell volumes were morphometrically determined. The experimental results confirm the deleterious impact of the Hst-1s/Hstws genotype on spermatogenesis and demonstrate for the first time that the steroidogenic capacity of hybrid sterile testes is reduced. The biochemical defects that cause the impairment of testicular function are unknown.

Animals↗

Cerebral cysticercosis: a case report with particular reference to recent advances in diagnosis and treatment.

Cerebral cysticercosis is becoming more common in Australia as the immigrant population from areas of endemic disease increases. The case reported exemplifies the common presentation of this interesting infestation. Treatment consists primarily of Praziquantel with or without steroids and anti-seizure medication if indicated. Follow-up is by both clinical and radiological assessment.

Australia↗

The effects of cisplatin on rat spinal ganglia: a study by light and electron microscopy and by morphometry.

Cisplatin given in doses of 0.5-2 mg to Wistar and to Sprague-Dawley rats produced nucleolar segregation of the dense fibrillar from the granular component in spinal root ganglion cells. The nucleolar segregation, found to the same extent in large and small neurons, was confirmed by specific silver staining and by electron microscopy. After repeated doses of 1 mg or 0.5 mg, up to 40% of affected nucleoli were observed by light microscopy. Focal clearing of the nucleoplasm of nuclei also occurred. Disorganisation of ribosomes was found in more severely intoxicated animals, especially in large light cells with shrinkage of the Nissl substance and apparent increase in neurofilaments, the latter occasionally distending the initial segment of the axon, but never extending further. Hypertrophy of the satellite cells with increase in the perineuronal intercellular spaces, often associated with irregular, scalloped nuclear and cell outlines, suggested that neuron shrinkage had occurred. This was confirmed by morphometry and marked alterations were found in nucleolar-to-nuclear and nucleolar-to-cell diameter ratios, nuclear and cell diameters were also somewhat reduced without change in the nucleus-to-cell ratios. Peripheral sensory nerve degeneration was not seen, and the animals died from non-neural causes. The probable role of these events in the production of sensory neuropathy is discussed.

Animals↗

Metabolism in the rat of cadmium biocomplexes from edible mussel exposed to 109CdCl2.

The metabolism in the rat of 109Cd biocomplexes present in the tissues of the edible mussel Mytilus galloprovincialis, previously exposed to 109CdCl2, was studied. The tissue distribution and binding of 109Cd were compared to those caused by an equal dose of 109Cd as CdCl2 or rat liver Cd-metallothionein. Administration of mussel 109Cd to rats resulted in an initial accumulation of 109Cd in the kidneys due to the presence of 109Cd-metallothionein, which constituted 25% of the 109Cd in the tissues of the mussels. Other 109Cd biocomplexes present in the mussel tissues were metabolized in the rat in a way similar to that of inorganic cadmium, i.e., initial accumulation in the liver. These findings indicate that the ingestion of seafood rich in metallothionein may give rise to a faster increase of renal cadmium levels than the consumption of a similar amount of inorganic cadmium.

Animals↗