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J Wiley

Publications and source records attributed to J Wiley.

At least 37 records · Page 2Linked to original sources
PubMed1997

Specific chromosomal changes in albumin simian virus 40 T antigen transgenic rat liver neoplasms.

Hepatocytes isolated from 3-month-old female rats bearing the albumin promoter/enhancer SV40 T antigen construct as a transgene demonstrated a 20% aneuploidy rate and a significant duplication of chromosome 1. Other chromosome changes were observed but were not statistically significant. At this time in the development of hepatic lesions, only a relatively small number of microscopic altered hepatic foci could be noted. By contrast, hepatocytes isolated from the age-matched nontransgenic controls demonstrated only 1% aneuploidy. One hundred % of the metaphase spreads isolated from hepatocellular neoplasms in transgenic rats were aneuploid. Although there were many random changes, 70% of the neoplastic cells demonstrated an amplification of all or portions of chromosome 1q. Only 2% of the neoplastic cells had both a trisomy and a duplication. The smallest region of chromosome 1 that was duplicated was that between bands q3.7 and q4.3. A loss of chromosome 3 was detected in 50% of the neoplasms, as well as a loss of chromosome 6 in 72% of the neoplastic cells. The carcinomas with the highest proliferation rate had also lost at least one copy of chromosome 15 in 70% of the cells. The loss of chromosomes 3, 6, and 15 indicates that these regions may harbor one or more tumor suppressor genes. The amplification of a specific region of chromosome 1 is thus the first karyotypic alteration that can be identified in hepatocytes from livers from which hepatic neoplasms will arise. This indicates that expression or repression of one or more genes in this region may confer a growth advantage to preneoplastic hepatocytes, facilitating their transit to the neoplastic state in the stage of progression. Changes in chromosomes 3, 6, and 15 that occur subsequent to duplication of the q3.7-q4.3 region of chromosome 1 are changes possibly reflecting alteration of tumor suppressor genes with further enhancement of neoplastic growth.

Animals↗
PubMed1997

Thromboelastographic changes in healthy parturients and postpartum women.

Thromboelastography (TEG) using disposable plastic cups and pins was performed with native whole blood (native group) in 17 nonpregnant volunteers, 134 healthy term pregnant women (>36 wk gestation), and 69 postpartum women. Thromboelastography was also performed with celite-activated whole blood (celite group) in 15 nonpregnant female volunteers, 38 healthy term pregnant women, and 34 postpartum women. The thromboelastographic parameters r and K were significantly decreased in pregnant and postpartum women compared with nonpregnant women in both groups (P < 0.05). The maximum amplitude MA, elastic shear modulus, and alpha angles were significantly increased in pregnant and postpartum women compared with nonpregnant women in both groups (P < 0.05). The TEG coagulation index was significantly greater in pregnant and postpartum women compared with nonpregnant women in both groups. In this study, TEG showed that pregnancy is a hypercoagulable state and that postpartum women remain hypercoagulable through the first 24 h postdelivery. The use of celite in TEG accelerated the speed of TEG analysis.

Blood Coagulation↗
PubMed1997

The functional phenotype of the primitive plasma cell in patients with multiple myeloma correlates with the clinical state.

The malignant plasma cells from patients with multiple myeloma display considerable phenotypic heterogeneity. All plasma cells express high intensity CD38 (CD38++), cytoplasmic immunoglobulin and either kappa or lambda light chains. Subpopulations of mature (CD45-), immature (CD45+) and primitive (CD45++, CD19+) plasma cells can be defined but little is known about the functional differences and clinical significance of these subpopulations. Three colour flow cytometry and permeabilisation was used to determine the expression of functionally important antigens in plasma cell subpopulations. These antigens included the labelling index (LI, bromodeoxyuridine), number of nucleoside transporter per cell, p-glycoprotein (JSB-1), and oncoprotein expression (c-myc, c-fos, c-neu, bcl-2, p-ras, p53m, p-53w, and Rb). In progressive disease there was an increase in the absolute number but not the percentage of CD45++ plasma cells. There was a significant difference in the mean LI of the CD38++, CD45++ population in progressive disease compared with stable disease (9.2% vs 2.2%; z = 19.9, p < 0.001). The LI of CD45++ cells ranged up to 45% and provided a better correlation with disease status than the LI of the total cell population. Any increase in nucleoside transporters or p-glycoprotein expression was almost entirely attributable to an increase in the primitive plasma cell population. In 96% (n = 28) of samples from patients in progressive disease there was at least one abnormality in the functional phenotype of the primitive plasma cells. This is in contrast with 44% of samples from patients in stable disease (n = 58). These studies suggest that the functional phenotype of the primitive plasma cell determines the clinical phenotype of patients with myeloma.

ADP-ribosyl Cyclase↗
PubMed1997

Collaborative multicenter investigation of marrow transplantation for sickle cell disease: current results and future directions.

We present updated results of a multicenter collaborative investigation of bone marrow transplantation for sickle cell disease. Between September 1991 and April 1997, thirty-four children less than 16 years of age with severe sickle cell disease received marrow allografts from HLA-identical siblings. Indications for transplantation included a history of stroke (n = 17), recurrent acute chest syndrome or sickle pulmonary disease (n = 10), and recurrent vaso-occlusive crises (n = 7). Twenty-one patients received regular red blood cell (RBC) transfusions to prevent complications of sickle cell disease. Patients were prepared for transplantation with busulfan, cyclophosphamide, and antithymocyte globulin or CAMPATH (Cambridge Pathology) antibody. Thirty-two of the 34 patients survived, with a median follow-up of 26.5 months (range, 0.2-66.9 months); and 28 patients demonstrated stable engraftment of donor hematopoietic cells. Graft rejection or recurrence of sickle cell disease occurred in four patients, and two patients died of intracranial hemorrhage or graft-vs.-host disease. In the group of 34 children with symptoms of advanced sickle cell disease, current Kaplan-Meier estimates of survival and event-free survival are 93% and 79%, respectively.

Adolescent↗
PubMed1996

Karyotypic changes in a multistage model of chemical hepatocarcinogenesis in the rat.

Karyotypic analysis of the stages of rat hepatocarcinogenesis has been facilitated by the development of an initiation-promotion-progression (IPP) protocol that permits separation and characterization of morphologically normal and altered hepatocytes in each of these three stages. The expression of the membrane antigen gamma-glutamyl transpeptidase (GGT) during the promotion and progression stages of rat hepatocarcinogenesis permits the isolation, culture, analysis, and comparison of hepatocytes in the two stages, which express this marker of carcinogenesis. Female rats were administered 10 mg diethylnitrosamine/kg at 5 days of age. One group of initiated rats was maintained on dietary phenobarbital admixed into a laboratory chow diet at 0.05% for 9 months after weaning (promotion protocol). This initiation-promotion (IP) group was compared with one subjected to the complete IPP protocol. The IPP group was initiated with diethylnitrosamine, maintained on phenobarbital for 6 months after weaning, and then subjected to a 70% partial hepatectomy and administered 100 mg ethylnitrosourea/kg 24 h later. These rats on the IPP protocol were then maintained on phenobarbital for an additional 3 months prior to sacrifice. At sacrifice, single hepatocyte suspensions were obtained and separated into populations of cells expressing or not expressing GGT. These hepatocyte populations were cultured separately and subjected to standard cytogenetic analysis. At least five animals per treatment and 100 metaphase spreads of good morphology per animal were examined. Although GGT- cells from the IP protocol were 80% tetraploid and 20% diploid, the GGT+ hepatocytes were greater than 90% diploid. The GGT+ cells from this protocol had a low rate of random aneuploidy (4.0 +/- 1.3%) compared with corresponding cells from the IPP protocol, but a higher level of background aneuploidy compared with GGT- cells from the IP protocol. The GGT+ hepatocytes from animals on the IPP protocol had a 35% incidence of aneuploidy. In addition, the GGT+ population had a 28 +/- 5% incidence of chromosomal breakage and a 17 +/- 5% incidence of chromosomal rearrangements. The primary nonrandom chromosomal changes observed in cells from the IPP protocol included duplication of all or part (1q37-43) of chromosome 1 and the loss of chromosomes 3p and/or 6q. These studies indicate that rat hepatocytes in the stage of promotion are euploid, whereas those in the stage of progression exhibit considerable genetic instability. The presence of multiple copies of chromosome 1 or a duplication of a region of this chromosome indicates that alteration of gene dosage for one or more of the genes present in this region is critical to the neoplastic conversion of rat hepatocytes, whereas the loss of all of 3p and the last light band of 6q may indicate the presence of tumor suppressor genes. Thus, the IP and IPP protocols coupled with the ability to isolate GGT+ and GGT- hepatocytes permit the differential cytogenetic characterization of the stages of promotion and progression in rat hepatocarcinogenesis.

Animals↗
PubMed1996

Cytogenetic analysis of three rat liver epithelial cell lines (WBneo, WBHa-ras, and WBrasIIa) and correlation of an early chromosomal alteration with insulin-like growth factor II expression.

Cytogenetic changes that occur during the progression of rat hepatocarcinogenesis were assessed with three rat liver epithelial cell lines derived from WB cells. Previously characterized WBneo, WBras, and WBrasIIa cells were grown in culture and analyzed for structural and numerical chromosomal integrity by banded karyotype analysis. The WBneo cells had a low level of aneuploidy with a consistent loss of the Y chromosome by passage 7. The ras-transfected cell line selected for growth in soft agar, WBras, had acquired a loss of chromosome 3 (12%) or 3p (34%), a trisomy of chromosome 1, as well as the chromosome Y loss. The cell line produced from tumors generated by injection of the WBras cells into a syngeneic F344 rat, WBrasIIa, contained additional chromosomal changes. The WBrasIIa line comprised cells retaining a trisomy of chromosome 1 (55%) and cells with two copies of chromosome 1, with a minimal duplication of 1q3.7 to 1q4.3 (45%). This tumor-derived cell line contained, in addition, a higher percentage of cells with a loss of all or part of chromosomes 3 and 6, indicating the possible presence of tumor suppressor genes in this region. The smallest region of duplication of chromosome 1 was bands 1q3.7-4.3. The insulin-like growth factor II (IGF-II) gene is located within the region of duplication on chromosome 1. Because IGF-II is both a rat liver mitogen and an inhibitor of apoptosis, its expression was examined in these three rat liver epithelial cell lines. Northern blot analysis demonstrated an increase in IGF-II mRNA expression in the WBras and WBrasIIa cell lines relative to the WBneo control cell line. Several IGF-II transcripts analogous to those detected in fetal rat liver were observed. An additional IGF-II transcript that migrates above the 28S ribosomal marker was also observed. These results were confirmed at the protein level by immunohistochemical and Western blot analysis. This increased expression of IGF-II may confer a selective growth advantage to rat liver epithelial cells with a duplication of 1q3.7-4.3. This growth advantage may be enhanced by the further sequential loss of putative tumor suppressor genes on chromosomes 3 and 6.

Animals↗
PubMed1996

Highly purified CD34-positive cells reconstitute hematopoiesis.

PURPOSE: The objective of this study was to characterize CD34+ cell grafts, obtained using a novel technique, from children undergoing autologous bone marrow transplantation (BMT) for cancer therapy. In particular, we wanted to determine if the CD34+ marrow cell grafts generated hematopoietic reconstitution, since a positive result would motivate further development and use of this methodology. PATIENTS AND METHODS: This pilot feasibility clinical trial involved 13 patients < or = 25 years of age with advanced solid tumors, including seven children with neuroblastoma. Harvested bone marrow underwent immunomagnetic CD34+ selection. RESULTS: In three of 13 enrolled patients, low purities of the CD34+ preparations disqualified the use of the CD34+ marrow grafts. Ten patients received myeloablative chemotherapy with etoposide, carboplatin, and cyclophosphamide, then were transplanted with CD34+ marrow grafts. In the 10 patients transplanted with CD34(+)-selected cells, the CD34+ cell purity (nucleated RBCs excluded) in the cell graft preparation was 91% total cell recovery from the starting light-density cells 2.2%, CD34+ cell recovery 38%, colony-forming unit-granulocyte-macrophage (CFU-GM) recovery 23%, and estimated tumor-cell depletion 2.6 logs (medians). The CD34+ marrow grafts administered to these patients contained a median of 2.3 x 10(6) nucleated cells, 1.4 x 10(6) CD34+ cells, and 1.3 x 10(4) CFU-GM per kilogram patient weight. Most patients experienced only the toxicities previously observed with this myeloblative chemotherapy regimen, although two unusual toxicities were observed. All 10 patients transplanted with CD34+ cell grafts engrafted. CONCLUSION: The CD34+ purified grafts were enriched in stem/progenitor cells, with five of these 10 preparations containing > or = 94% CD34+ cells. Engraftment with CD34(+)-purified cell grafts as pure as 99% confirms that autologous CD34+ cells, alone, are sufficient to provide hematopoietic rescue for myeloablated patients. The best purification results were obtained on small marrow harvests from patients with neuroblastoma. The engraftment of highly purified CD34+ cells obtained by this technology and the antitumor effect of the transplant, by which two of 10 poor prognosis patients remain clinically free of tumor, have stimulated further clinical trials.

Adolescent↗
PubMed1995

Discriminative stimulus effects of anandamide in rats.

Anandamide (arachidonylethanolamide), a putative endogenous ligand for the cannabinoid receptor, produces a tetrad of behavioral effects in mice characteristic of psychoactive cannabinoids including catalepsy, antinociception, hypothermia, and hypomobility. The present study examined the discriminative stimulus effects of anandamide in rats trained to discriminate delta 9-tetrahydrocannabinol or the potent cannabinoid receptor ligand CP 55,940 [(-)-cis-3-[2-hydroxy-4-(1,1-dimethylheptyl)-phenyl]-trans-4-(3- hydroxypropyl)cyclohexanol)] from vehicle. Intraperitoneal injections of anandamide substituted for delta 9-tetrahydrocannabinol and for CP 55,940; however, unlike substitution dose-effect curves with the training drugs, anandamide substitution occurred at a single dose (30 or 45 mg/kg) and was accompanied by severe decreases in response rates. The results of the present study suggest that, although systemic anandamide administration may have cannabimimetic effects similar to those of delta 9-tetrahydrocannabinol and CP 55,940, some differences in the behavioral effects of anandamide and other psychoactive cannabinoids also are apparent.

Animals↗
PubMed1995

Cytogenetic and flow cytometric analysis of a pancreatoblastoma.

A pancreatoblastoma from a 4-year old male was examined by flow cytometric ploidy analysis and cytogenetics. To detect differences within the tumor, the specimen was divided into four portions and sampled separately. Flow analysis revealed that each sample contained a diploid and a tetraploid population of tumor cells. These findings correlated well with the cytogenetic analysis, which also revealed differences in structural rearrangements between samples. A t(13;22)(q10;q10) was the only rearrangement found in near-diploid cells as well as one near-tetraploid line. Other common structural changes in near-tetraploid cells included t(13;13)(q10;q10), i(6p)(p10), and del(1). Chromosomes 1, 6, 13, and 22 were consistently missing from all near-tetraploid cells lines. To our knowledge, this is the first flow cytometric and cytogenetic study of a pancreatoblastoma.

Child, Preschool↗
PubMed1995

A clinical and pharmacokinetic study of high-dose carboplatin, paclitaxel, granulocyte colony-stimulating factor, and peripheral blood stem cells in patients with unresectable or metastatic cancer.

We have developed a regimen incorporating multiple cycles of high-dose carboplatin and fixed-dose paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) with granulocyte colony-stimulating factor and peripheral blood stem cell support given every 21 days for up to four cycles. Our phase I study of this regimen has treated 26 patients with good performance status and histologically documented unresectable or metastatic carcinoma, sarcoma, or melanoma, 21 of whom received all planned courses every 21 days. Paclitaxel 250 mg/m2 was infused over 24 hours, followed by a 1-hour carboplatin infusion, with doses escalated between area under the concentration-time curve (AUC) targets of 8 and 20. Considering the carboplatin doses administered (two to three times those generally achieved with growth factor support), toxicity has been relatively modest. The median duration of grade 4 neutropenia and thrombocytopenia was not significantly different between the AUCs of 8 and 18, which proved to be the maximum tolerated carboplatin dose. Twelve courses were associated with hospitalization for neutropenic fever or catheter-related thrombophlebitis. One treatment-related death occurred, and severe toxicity caused withdrawal of two patients treated at the AUC of 20. Peripheral neuropathy was the most common serious nonhematologic complication. Pharmacokinetic analysis showed significantly lower measured versus predicted AUC values. Among 25 evaluable patients, preliminary results show one complete response (ovarian cancer) and 11 partial responses, including four in patients with non-small cell lung cancer. Additional issues to be addressed include the effect of a shorter (or longer) paclitaxel infusion on the carboplatin AUC (and the incidence of toxicity) and whether the discrepancy between actual and predicted AUCs (greater in our study than reported elsewhere) is due to the variability of creatinine clearance-determined glomerular filtration rate or to altered carboplatin pharmacokinetics when a short high-dose infusion follows paclitaxel. Additional patients are being accrued at the AUC of 18.

Adult↗
PubMed1994

HIV infection in homosexual and bisexual men 18 to 29 years of age: the San Francisco Young Men's Health Study.

OBJECTIVES: Recent studies suggest very high human immunodeficiency virus (HIV) infection rates in some populations of younger homosexual men, but these studies may represent only particularly high-risk populations. The current study obtained population-based data on the HIV epidemic in young homosexual/bisexual men. METHODS: A household survey of unmarried men 18 through 29 years of age involved a multistage probability sample of addresses in San Francisco. A follow-up interview and HIV test for men who were HIV negative at baseline were completed; the median follow-up was 8.9 months. RESULTS: Sixty-eight of 380 homosexual/bisexual men (17.9%) tested HIV seropositive. Sixty-three percent of men reported one or more receptive anal intercourse partners in the previous 12 months, and 41% of those men did not use condoms consistently. The HIV seroincidence rate among those seronegative at first study was 2.6% per year. CONCLUSIONS: HIV infection rates in young homosexual men in San Francisco are lower than those in the early 1980s; however, the rate of infection in these men, most of whom became sexually active after awareness of AIDS had become widespread, threatens to continue the epidemic in the younger generation at a level not far below that of a decade ago.

Adolescent↗
PubMed1993

Mosaic tetrasomy 8p.

We report on a patient with mosaic tetrasomy 8p [46,XX/47,XX+i(8p)]. The patient has 2 fused vertebrae, abnormal ribs, congenital heart defects, agenesis of corpus callosum, hypotonia, and delayed development. The patient's developmental delays are most marked in receptive and expressive language skills, with more moderate delays on cognitive, sensorimotor, and motor skill testing. These findings are similar to those of the 3 previously reported patients with mosaic i(8p).

Abnormalities, Multiple↗
PubMed1993

Inhibition by a stable factor derived from neutrophils of endothelium-dependent relaxation in rat aorta.

Polymorphonuclear leukocytes (PMNs) may play an important role in many pathophysiological states. The effect of a factor derived from PMNs on endothelium-dependent relaxation was studied using rat aortic rings in organ chambers. PMNs were obtained from cardiac surgical patients and healthy volunteers. After incubation in Krebs solution for 3 h, supernatants of PMN suspensions were isolated and used to pretreat the aortic rings for 30 min. The results showed that the supernatants derived from 1 x 10(4) to 5 x 10(6) cells/ml PMNs produced a concentration-dependent inhibition of endothelium-dependent relaxation to acetylcholine but not endothelium-independent relaxation to sodium nitroprusside. The effect could not be prevented by oxygen free radical scavenger superoxide dismutase (150 U/ml), catalase (1,200 U/ml), or mannitol (20 mM) used alone or in combination. Heating the supernatants at 95 degrees C for 30 min did not reduce the inhibitory effect. L-Arginine at 3 x 10(-5) to 3 x 10(-3) M did not significantly reverse the inhibitory effect of the PMN-derived factor. In conclusion, this study reveals that a heat-stable factor derived from human PMNs potently inhibits acetylcholine-induced endothelium-dependent relaxation but not sodium nitroprusside-induced endothelium-independent relaxation in rat aorta. This inhibitory effect is not caused by oxygen free radicals, a limitation of nitric oxide precursor or other unstable factors.

Animals↗
PubMed1992

Prevalence of AIDS-related risk factors and condom use in the United States.

A national probability survey of human immunodeficiency virus (HIV)-related risk factors among the general heterosexual population, the National AIDS (acquired immunodeficiency syndrome) Behavioral Surveys, has obtained data from 10,630 respondents. Data are presented on the prevalence of HIV-related risks in the general heterosexual population, on the distribution of the three largest risk groups across social strata, and on the prevalence and distribution of condom use among heterosexuals reporting a risk factor. Between 15 and 31 percent of heterosexuals nationally and 20 and 41 percent in cities with a high prevalence of AIDS reported an HIV risk factor. Condom use was relatively low. Only 17 percent of those with multiple sexual partners, 12.6 percent of those with risky sexual partners, and 10.8 percent of untested transfusion recipients used condoms all the time. Overall, the results suggest that current HIV prevention programs have, to a very limited extent, reached those heterosexuals with multiple sexual partners but have failed to reach many other groups of the heterosexual population at risk for HIV. New public health strategies may be needed for these specific risk groups.

Acquired Immunodeficiency Syndrome↗