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N Solomon

Publications and source records attributed to N Solomon.

At least 19 recordsLinked to original sources

The glucocorticoid receptor is essential for maintaining basal and dexamethasone-induced repression of the murine corticosteroid-binding globulin gene.

We have investigated hepatic expression and glucocorticoid regulation of the corticosteroid-binding globulin (CBG) gene in mice lacking a functional glucocorticoid receptor (GR). GR-/- mice show impaired negative feedback in the hypothalamic-pituitary-adrenal axis, resulting in elevated circulating levels of ACTH and corticosterone. This is seen in the neonatal period and continues into adulthood where ACTH and corticosterone levels are increased up to 4-5 fold. Despite high elevation of corticosterone we find no change in mean arterial blood pressure in GR-/- mice and no change in the renal activity of the glucocorticoid-metabolising enzymes 11beta-hydroxysteroid dehydrogenase type-1 (HSD1) and type-2 (HSD2). We do find markedly increased hepatic expression of CBG with a 50% increase in plasma CBG levels. Increased expression of CBG was detected in adult GR-/- mice and also at birth with a greater than 10-fold increase in CBG hepatic mRNA in day-18.5 embryonic GR-/- mice. Adult GR-/- mice were also resistant to dexamethasone-induced repression of CBG expression in the liver. These results indicate that in mice, GR is essential for maintaining the basal level of CBG gene expression in the liver, and is also required for dexamethasone-induced repression of the CBG gene in the adult.

Adrenocorticotropic Hormone

Detection of GB virus C by the RT-PCR LCx system.

The recent publication of representative genomic sequences of GBV-C has permitted the selection of PCR primers for detection of GBV-C in clinical samples by PCR techniques. Traditional amplification methodologies which couple reverse transcription polymerase chain reaction (RT-PCR) and Southern blot detection are slow, cumbersome, and can be technique dependent. This has hampered studies to determine the clinical significance of GBV-C. We report the selection of highly conserved PCR primers and a probe useful for semi-automated RT-PCR using the Abbott LCx system. This adaptation of the LCx system expands its capabilities to include the detection of RNA by RT-PCR, in addition to DNA detection by ligase chain reaction (LCR).

Automation

Exposure to GB virus type C or hepatitis G virus in selected Australian adult and children populations.

BACKGROUND: The epidemiology and disease association for the GB virus type C (GBV-C) or hepatitis G virus (HGV) are poorly understood. STUDY DESIGN AND METHODS: This study describes the exposure rates to GBV-C/HGV in diverse Australian population groups by testing for current infection and evidence of past infection with a reverse transcriptase polymerase chain reaction and an anti-E2 enzyme-linked immunosorbent assay, respectively. Subjects included volunteer blood donors, hepatitis C antibody (anti-HCV)-positive donors, children, hemodialysis patients, pregnant women attending a prenatal clinic, injecting drug users (IVDUs), and adult hemophiliacs. RESULTS: Combined GBV-C RNA and E2 antibody prevalence was 6.5 percent (6/93) in children, 13.3 percent (75/565) in blood donors, 14 percent (14/99) in pregnant women, 22.5 percent (18/80) in hemodialysis patients, 80 percent (56/70) in anti-HCV-positive donors, 88.6 percent (31/35) in IVDUs, and 85.7 percent (54/63) in adult hemophiliacs. Children had the lowest antibody rate, 1.1 percent, whereas the rate was 10.8 percent for blood donors and rose to 45.7 percent for IVDUs, 57.1 percent for anti-HCV-positive donors, and 74.6 percent for hemophiliacs. In contrast, current infection rates were comparable for children, blood donors, and pregnant women (5.4, 2.6, and 6%, respectively), rising to 11.1 percent for hemophiliacs, 24.3 percent for anti-HCV-positive donors, and 48.6 percent for IVDUs. Ten of 12 blood donors had persistent viremia, while 2 had recent infections, 1 with apparent resolution. CONCLUSION: Exposure to GBV-C can commence at an early age, although ongoing exposure may also occur among adults with no apparent risk factors. GBV-C RNA positivity was not associated with abnormal plasma alanine aminotransferase levels among blood donors.

Adult

GB virus C/hepatitis G virus infection: a favorable prognostic factor in human immunodeficiency virus-infected patients?

To investigate a possible influence of GB virus C (GBV-C) in immunocompromised patients, the prevalences of GBV-C RNA and anti-E2 antibody in 197 human immunodeficiency virus (HIV)-infected patients and in 120 control blood donors were studied. GBV-C RNA was detected in 33 of 197 HIV-infected patients (16.8%) compared with 1 in 120 blood donors (0.8%) (P < .001). Previous exposure to GBV-C (anti-E2 antibody-positive) was shown in 56.8% of HIV patients and in 9% of blood donors. GBV-C viremia was not associated with hepatitis. Despite approximately equal duration of HIV infection in all subgroups, the CD4 cell counts were significantly higher in GBV-C-viremic patients (344 cells/microL) compared with exposed (259 cells/microL) and unexposed (170 cells/microL) patients (P = .017 and P < .001). Furthermore, Kaplan-Meier analysis demonstrated significantly better cumulative survival in GBV-C RNA-positive HIV-infected patients, suggesting that GBV-C might be a favorable prognostic factor in HIV disease.

AIDS-Related Opportunistic Infections

Prevalence of stroke and stroke-related disability. Estimates from the Auckland stroke studies.

BACKGROUND AND PURPOSE: To provide estimates of the prevalence of stroke and stroke-related disability for international comparisons and for planning purposes. METHODS: Estimates of prevalence were derived from two population-based studies conducted 10 years apart in Auckland, New Zealand. The first, carried out in 1981, included information on survival and stroke-related disability to 14 years after stroke, and the second, undertaken in 1991 to 1992, included this information up to 3 years after stroke. An actuarial model was developed that took into account changes in incidence, long-term survival, and population structure. RESULTS: Overall, it was estimated that 7491 people (3793 men and 3698 women) living in Auckland (total population 945,000) in 1991 had experienced a stroke at some stage in the past. This represents an age-standardized rate of 833 per 100,000 (991 per 100,000 in men and 706 per 100,000 in women) in the population aged 15 years and older. When only those who have made an incomplete recovery are considered, prevalence falls to 461 per 100,000. Of this group, one third (173 per 100,000 population 15 years and older) required assistance in at least one self-care activity. CONCLUSIONS: Usual estimates of stroke prevalence, which include all people who have ever experienced a stroke, may overestimate by almost twofold the prevalence of stroke-related disability, since many have either recovered or have no continuing dependency related to stroke. Overall prevalence does not provide information with sufficient precision for planning and purchasing ongoing services for stroke patients.

Activities of Daily Living

A genetic analysis of the 63E-64A genomic region of Drosophila melanogaster: identification of mutations in a replication factor C subunit.

We have performed an F2 genetic screen to identify lethal mutations within the 63E-64A genomic region. We have isolated 122 mutations in 20 different complementation groups. Of these groups, 16 are represented by multiple alleles. We have also established that the Rop and Ras2 genes are located within the 63E-64A genomic domain at 64A10,11. We have sequenced 10.2 kb of DNA surrounding this gene pair and find that in addition to Rop and Ras2 there is another gene located within this DNA sequence. The gene product, which we have named Rfc40, shows 68% identity to the 40-kDa subunit of replication factor C. We find that the members of one complementation group (13 alleles) derived from our screen correspond to mutations in the Rop gene, whereas the members of another (five alleles) correspond to mutations in the Rfc40 gene. In addition we have isolated 11 new mutant alleles of the disembodied gene.

Amino Acid Sequence

Cancer rates.

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Humans

Incidence of cancer among Pacific Island people in New Zealand.

AIM: to describe the epidemiology of new cancer registrations among Pacific Island people in New Zealand with a view to identifying important cancers for preventive activities. METHODS: new cancer cases registered with the New Zealand Cancer Registry of the Health Statistical Services for the decade 1979-88 were analysed. Cancer cases among Pacific Island people were compared with cancer cases among Maori and the remainder of the New Zealand population (other). RESULTS: while the number of cases reported among Pacific Island people was relatively small (1884), age standardised rates for cancer of all sites were much higher than age standardised rates for Maori and other populations. The age standardised rate (per 100,000 person years) for cancer of all sites among males in all age groups was 400 for Pacific Island, 308.8 for Maori and 295.3 for others. The age standardised rate for cancer of all sites among women in all age groups was 373.3 for Pacific Island women, 324.2 for Maori and 313.4 for other women. Liver cancer was more common among Pacific Island men than could be explained by temporary migration from the Pacific Islands for treatment. The age standardised rate for liver cancer was 28.2 for Pacific Island men, 11.4 for Maori and 1.9 for other men. Cancer of the cervix was the leading site among Pacific Island women as in Maori women, compared with breast cancer among women in the rest of the population. The age standardised rate for cervical cancer was 61.8 for Pacific Island, 69.0 for Maori and 59.3 for other women. CONCLUSION: in the decade 1979-88 there was an excess number of new registrations for some cancers described among Pacific Island people compared with Maori and other ethnic groups. Temporary migration from the Pacific Islands for treatment may explain some of the excess cases.

Adolescent

The consequences of expressing hsp70 in Drosophila cells at normal temperatures.

In Drosophila cells, regulatory mechanisms not only act to provide rapid induction of hsp70 during heat shock but also to prevent expression at normal temperatures. To determine whether expression of hsp70 is detrimental to cells growing at normal temperatures, we used heterologous promoters to force expression of the protein in tissue culture cells and in larval salivary glands. Initially, constitutive expression of hsp70 substantially reduces the rate of cell growth. With continued expression, however, growth rates recover. At the same time, the intracellular distribution of hsp70 changes. Immediately after induction, the protein is diffusely distributed throughout the cell, but as growth resumes it coalesces into discrete points of high concentration, which we term hsp70 granules. hsp70 granules are also observed both in wild-type Drosophila tissue culture cells and in salivary glands after extended periods of recovery from heat shock. The protein in these granules appears to be irreversibly inactivated. It cannot be dispersed with a second heat shock, and cells containing these granules do not show thermotolerance. Only partial overlap between hsp70 granules and lysosomes indicates that the granules form independently of lysosomes. We conclude that expression of hsp70 is detrimental to growth at normal temperatures. We suggest that the change in hsp70 distribution, from diffuse to granular, represents a mechanism for controlling the protein's activity by sequestration.

Animals

Intravascular stents in the management of superior vena cava syndrome.

Superior vena cava syndrome can be effectively palliated with the use of intravascular stents. Adjunctive modalities which may be utilized prior to stent placement are thrombolytic therapy and balloon angioplasty. Six patients with an underlying malignancy were treated with these modalities. Complete resolution of symptoms occurred in five patients, and partial resolution occurred in the sixth. Two of the patients who had initial, complete resolution of symptoms had recurrences. One involved rethrombosis of the superior vena cava which occurred twice and required percutaneous thrombectomy, and the second involved restenosis requiring a percutaneous transluminal angioplasty of the SVC just distal to the stent. Both of these patients with second procedures, again, had complete resolution of symptoms. Intravascular stents are a valuable additional treatment of superior vena cava syndrome.

Adult

Breast cancer incidence and mortality in Auckland, 1981-6.

Age standardised incidence and mortality rates were calculated for breast cancer for the Auckland area. Incidence of female breast cancer for 1981-4 was significantly higher in Auckland compared with all New Zealand, with a standardised incidence ratio of 1.11. While total incidence was the same across the three Auckland districts, there were wide discrepancies in mortality rates. Women in Takapuna had a far lower risk of dying of breast cancer compared with all New Zealand for 1981-6 and had a standardised mortality ratio of 0.86. Central Auckland and south Auckland women had increased risks--1.10 and 1.18 respectively. Similar discrepancies were evident in the important 45-64 age group. Possible reasons for the reported differences are discussed with socioeconomic factors seeming the most likely agency.

Age Factors

Scintigraphic differentiation of bone infarction from osteomyelitis in children with sickle cell disease.

Bone scans or bone marrow scans or both were obtained during 42 episodes of bone pain in 40 children with sickle cell disease, and the usefulness of these procedures was compared. On the basis of the subsequent clinical course, a diagnosis of bone infarction was made in 34 episodes, and osteomyelitis in eight. Among 22 patients with bone infarction, uptake on bone scan was increased in 14, decreased in three, and normal in five. Seven of eight patients with osteomyelitis had increased uptake on bone scan; one had normal uptake. In contrast, marrow scan uptake was markedly decreased in 15 of 16 patients with bone infarction, and was normal in five of five patients with osteomyelitis. Thus, decreased uptake on bone marrow scan in a patient with sickle cell disease and bone pain almost invariably indicates infarction, whereas normal uptake strongly suggests the diagnosis of osteomyelitis. We found marrow scans more useful than bone scans for this differential diagnosis.

Adolescent

Kinetics and energetics of intramolecular electron transfer in yeast cytochrome c peroxidase.

The oxidation of ferric cytochrome c peroxidase by hydrogen peroxide yields a product, compound ES [Yonetani, T., Schleyer, H., Chance, B., & Ehrenberg, A. (1967) in Hemes and Hemoproteins (Chance, B., Estabrook, R. W., & Yonetani, T., Eds.) p 293, Academic Press, New York], containing an oxyferryl heme and a protein free radical [Dolphin, D., Forman, A., Borg, D. C., Fajer, J., & Felton, R. H. (1971) Proc. Natl. Acad. Sci. U.S.A. 68, 614-618]. The same oxidant takes the ferrous form of the enzyme to a stable Fe(IV) peroxidase [Ho, P. S., Hoffman, B. M., Kang, C. H., & Margoliash, E. (1983) J. Biol. Chem. 258, 4356-4363]. It is 1 equiv more highly oxidized than the ferric protein, contains the oxyferryl heme, but leaves the radical site unoxidized. Addition of sodium fluoride to Fe(IV) peroxidase gives a product with an optical spectrum similar to that of the fluoride complex of the ferric enzyme. However, reductive titration and electron paramagnetic resonance (EPR) data demonstrate that the oxidizing equivalent has not been lost but rather transferred to the radical site. The EPR spectrum for the radical species in the presence of Fe(III) heme is identical with that of compound ES, indicating that the unusual characteristics of the radical EPR signal do not result from coupling to the heme site. By stopped-flow measurements, the oxidizing equivalent transfer process between heme and radical site is first order, with a rate constant of 0.115 s-1 at room temperature, which is independent of either ligand or protein concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

Cytochrome-c Peroxidase