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Biomedical subjects

A Wu

Publications and source records attributed to A Wu.

At least 181 records · Page 10Linked to original sources

Integrated human T-cell leukemia virus II genome in CD8 + T cells from a patient with "atypical" hairy cell leukemia: evidence for distinct T and B cell lymphoproliferative disorders.

We previously reported isolation of human T-cell leukemia virus II (HTLV-II) from a second patient (N.R.A.) with atypical hairy cell leukemia. Follow-up analysis of the characteristics of the patient's HTLV-II infection over a 2-year period has revealed that the patient had two coexistant lymphoproliferative disorders. Oligoclonally integrated HTLV-II was detected in DNA extracted from the patient's peripheral blood mononuclear cells on separate occasions greater than 1 year apart, similar to integration of HTLV-I seen in adult T cell leukemia/lymphoma. Although integrated provirus was readily detected, no HTLV-II viral RNA expression was seen in fresh peripheral blood lymphoid cells. Although the patient's peripheral blood consistently contained a majority of atypical lymphoid cells with a T cell antigenic phenotype, he ultimately developed extensive pleural, hepatic and soft tissue infiltration with malignant Tac+, tartrate-resistant, acid phosphatase-positive (TRAP+) B cells of clonal origin. To further characterize the role of HTLV-II, the patient's peripheral blood mononuclear cells were fractionated into four enriched subpopulations at autopsy. Oligoclonally integrated HTLV-II was detected in DNA from a T cell-enriched fraction and a CD8+ T cell-enriched fraction, but not in a CD4+ T cell-enriched fraction, a non-T cell fraction, or in B cells obtained from the malignant pleural effusion. We conclude that the patient harbored two distinct lymphoproliferative disorders, a TRAP+, Tac+ B cell malignancy consistent with hairy cell leukemia that did not contain HTLV-II and a Tac-, CD8+ lymphoproliferative syndrome with oligoclonally integrated HTLV-II.

Aged↗

Effects of acute hypoxia and reoxygenation in a blood-perfused neonatal heart model.

Newborn (less than 4-day old) piglet hearts (n = 7) were isolated and perfused with blood from a support pig. With use of a reservoir and membrane oxygenator, each heart was perfused for 90 minutes with blood at an O2 saturation of 40% and a pH of 7.4-7.5, at a left atrial pressure of 9 mm Hg, and at an aortic root pressure of 80 mm Hg. Blood saturation was increased to 100%, and the left atrial pressure decreased to 6 mm Hg for 60 minutes. Minute work indexes were calculated for each heart before hypoxia, every 30 minutes during hypoxia, and at 30 and 60 minutes of reoxygenation. Control hearts (n = 8) were treated in an identical fashion, but O2 saturation was maintained at 100%. Myocardial function decreased in the neonatal hearts exposed to hypoxia and reoxygenation. Control hearts did not suffer any significant decrease in function. Nucleotide levels were similar in both groups at the completion of the experiment. Anaerobic metabolism was demonstrated in the hypoxic hearts by net release of lactic acid during the period of hypoxia. This model can be used to study methods of intervention in the working hypoxic neonatal heart.

Acute Disease↗

Antineoplastic drug cytotoxicity in a human bladder cancer cell line: implications for intravesical chemotherapy.

The clonogenic survival of MGH-U1 human bladder carcinoma cells treated with melphalan, cisplatin, mitomycin-C, adriamycin, vincristine and 5-fluorouracil was measured to determine the relative contribution of drug concentration and duration of exposure to cytotoxicity and to measure the relative cytotoxic effects of these agents used in intravesical chemotherapy. The survival curves were plotted as a function of log (C X T) and were fitted using a linear least squares analysis. The survival was the same for any given C X T whether this was determined by varying concentration or by varying the duration of exposure in the cases of melphalan, cisplatin, adriamycin, mitomycin-C and 5-fluorouracil. However, duration of exposure was more important than was drug concentration in the case of vincristine cytotoxicity. By utilizing the slope of the log (survival fraction) as a function of log (C X T), the relative cytotoxicity of each agent was determined. Mitomycin C, melphalan, adriamycin and cisplatin had comparable activity in this cell line, whereas vincristine and 5-fluorouracil demonstrated much lower cytotoxicity. We conclude that: mitomycin-C, adriamycin and melphalan were the agents with the greatest cytotoxic efficacy; determination of survival as a function of C X T can be used to separate the relative importance of concentration and of duration of exposure. the cytotoxicity of 5/6 drugs studied was equal when the C X T was kept constant but concentration and exposure times were varied.

Administration, Intravesical↗

Stability of heating temperature on cytotoxicity.

Chinese hamster V79 cells were used to test the cytotoxic effect of heat which alternates between high and low temperatures during the treatment period. This type of temperature fluctuation is often encountered in clinical hyperthermia. Two sets of heating protocols were used in the experiments: Temperature alternates (a) between 42 and 43 degrees and (b) between 42 and 44 degrees in cycle with equal total "thermal dose," that is heating temperature X heating time. The effectiveness of these heating protocols expressed in average percentage of cell survival depend on the initial temperature attained and the length of the time of this temperature alternation. If the period of temperature change is short such as every 5 or 10 minutes, the cytotoxicity shows very little difference whether the initial treatment temperature is low or high. However, when the period is longer than 20 minutes, the difference in cell survival between the initial temperature at 42 degrees and at higher temperatures is substantial. Cells obtained from logarithmic or plateau phases of growth yield the same result. The difference is likely resulted from a combination of thermotolerance and step-down heating mechanisms. In addition, the effects of heating temperature fluctuation on cytotoxicity is not altered by a 500 cGy of gamma-ray radiation applied either immediately before or after the heat treatment.

Animals↗

Concurrent presence of two clonal populations in small lymphocytic lymphoma of the lung.

In a patient with small lymphocytic proliferation (SLP) involving the right middle and right lower lobes of the lung, immunophenotypic studies showed that the neoplastic lymphoid cells in the right middle lobe expressed kappa light chains, whereas those in the right lower lobe expressed lambda light chains on their surface. Gene rearrangement studies with Southern-blot hybridization confirmed the disparate surface immunoglobulin expression, and showed that the SLPs in the two lobes were derived from separate clones. The findings indicate that even morphologically identical lymphomas in the same organ may be immunophenotypically and genotypically heterogeneous. Our findings demonstrate that immunologic and DNA gene rearrangement analyses may complement each other in the study of lymphomas. This case is unique in that it is the first reported case of the concurrent presence of two immunologically distinct clonal populations in an extranodal site.

B-Lymphocytes↗

Sonography of pelvic masses in children: diagnostic predictability.

The usefulness of sonography in determining the location and internal consistency of a pelvic mass and in predicting a specific diagnosis was assessed in 70 girls ranging in age from neonate to 19 years. Sonography was correct in determining the site of origin in 39 of 40 surgically proven cases. Among the various sonographic patterns observed, cystic uterine masses and cystic adnexal masses were the most specific, representing hydrometrocolpos or intrauterine pregnancy and benign ovarian cysts, respectively. A nonspecific sonographic pattern was encountered with complex or solid adnexal masses, which were proven to be ovarian teratomas, hemorrhagic ovarian cysts, and pelvic abscesses. Occasionally, a specific diagnosis of ovarian teratoma could be made when echogenic foci produced shadowing in a complex adnexal mass. Our results indicate that sonography in girls is reliable in determining the site of origin of a mass and can suggest a specific diagnosis of hydrometrocolpos, benign ovarian cyst, or intrauterine pregnancy.

Abscess↗

Leu-9 (CD 7) positivity in acute leukemias: a marker of T-cell lineage?

Monoclonal antibody Leu-9 (CD 7) has been reported to be a sensitive and specific marker for T-cell lineage in leukemic processes, since it is positive in patients whose leukemic cells fail to express other T-cell antigens. To test whether Leu-9 is indeed specific for T-cell leukemias, we examined in detail 10 cases of acute leukemia in which reactions were positive for Leu-9 and negative for other T-cell-associated markers including T-11, Leu-1, T-3, and E-rosettes. Morphologically and cytochemically, 2 of these 10 leukemias were classified as lymphoblastic, 4 as myeloblastic, 2 as monoblastic, 1 as megakaryoblastic, and 1 as undifferentiated. The case of acute megakaryoblastic leukemia is the first reported case to be Leu-9 positive. None of the 10 were TdT positive. Of six cases (two monoblastic, one lymphoblastic, one myeloblastic, one megakaryoblastic, and one undifferentiated) in which we evaluated for DNA gene rearrangements, only one, a peroxidase-positive leukemia, showed a novel band on study of the T-cell-receptor beta-chain gene. We therefore conclude that Leu-9 is not a specific marker to T-cell lineage and that, in the absence of other supporting data, Leu-9 positivity should not be used as the sole basis of classifying an acute leukemia as being T-cell derived.

Acute Disease↗

Rearrangement of kappa-chain and T-cell receptor beta-chain genes in malignant lymphomas of "T-cell" phenotype.

Detection of immunoglobulin gene rearrangements by molecular hybridization is considered to be a highly sensitive approach to the evaluation of clonality of B-cell-derived neoplasms. Like monoclonal surface immunoglobulin in B cells, which serves as a reliable immunophenotypic marker for clonality, rearrangement of the genes encoding immunoglobulin light chains has been accepted as a reliable genotypic marker for the presence of a clonal expansion of B lymphocytes. The authors now report 3 cases of non-Hodgkin's lymphoma that were immunologically classified as having a T-cell phenotype and in which, in addition to rearrangements of the T-cell receptor beta-chain gene, a rearrangement of an immunoglobulin light-chain gene was clearly identified by Southern blot hybridization. The results demonstrate that the data obtained by molecular hybridization should be interpreted with caution when the immunogenetic findings do not correlate with immunophenotypic expression, and that the results of molecular genetics studies should be interpreted in conjunction with morphologic and immunologic findings.

Aged↗

Fetal malignant melanoma: ultrasound presentation and review of the literature.

Malignant melanoma is an infrequently described type of congenital neoplasm. We report a case of primary fetal malignant melanoma. A review of the literature yielded six previous cases, four of which were due to metastasis from advanced maternal disease, and two of which were fetal (primary) in origin. Recommendations are discussed for management of this rare fetal malignancy.

Adult↗

Membrane tolerance to ethanol is rapidly lost after withdrawal: a model for studies of membrane adaptation.

The structural properties of liver microsomes and erythrocytes obtained from rats that had been chronically administered ethanol were examined by electron spin resonance (ESR) following ethanol withdrawal for 1-10 days. Membranes obtained from control animals exhibited considerable molecular disordering upon the addition of ethanol in vitro (50-100 mM). Conversely, microsomal and erythrocyte membranes from alcoholic animals were resistant to this disordering by ethanol (membrane tolerance). These membrane properties were also apparent in lipid bilayers comprised of either total lipids or phospholipids isolated from the control and alcoholic animals. While several weeks of ethanol administration were required for both erythrocytes and microsomes to develop membrane tolerance, erythrocytes from alcoholic animals were disordered by ethanol in vitro after the animals had been withdrawn from ethanol for only 1 day. The same rapid loss of tolerance was observed in microsomes after 2 days of withdrawal. The same time course for the loss of tolerance was observed in lipid bilayers prepared from the total lipid and phospholipid extracts. No significant differences in the cholesterol/phospholipid ratio were observed between the microsomal or erythrocyte membranes isolated before and after withdrawal. Thus, alterations in the microsomal and erythrocyte phospholipids, and not cholesterol content, were responsible for conveying membrane tolerance. Membrane structural properties can be rapidly adjusted in a mammalian system in response to the withdrawal of the external membrane perturbant ethanol. The withdrawal model, which begins with established membrane tolerance and leads to rapid and complete loss of tolerance, provides a model to analyze the compositional changes responsible for this tolerance to disordering by ethanol.

Adaptation, Physiological↗

Immunoglobulin and T-cell receptor beta-chain gene rearrangement analysis of Hodgkin's disease: implications for lineage determination and differential diagnosis.

The lineage and clonality of Hodgkin's disease (HD) were investigated by analyzing the organization of the immunoglobulin and T-cell receptor beta-chain (T beta) gene loci in 18 cases of HD, and for comparison, in a panel of 103 cases of B- and T-cell non-Hodgkin's lymphomas (NHLs) and lymphoid leukemias (LLs). Sizable clonal B- or T-cell populations, representing greater than or equal to 10% of the pathologic sample, were readily detectable by immunogenotypic analysis in all 103 NHLs and LLs but not in any of the 18 cases of HD. However, extremely minor clonal populations (less than or equal to 1%) were detectable in 3 of 18 cases of HD. We demonstrated that these minor clonal populations do not correspond to Reed-Sternberg (RS) cells since clonal immunoglobulin or T beta gene rearrangements are not detectable in cases of HD containing greater than 25% RS cells. The number of RS cells present in these samples appeared to correlate directly with the pattern of gene rearrangements characteristic of polyclonal T cells. These studies demonstrate that Southern blot hybridization analysis for clonal immunoglobulin and T beta gene rearrangements represents an accurate, objective tool in the differential diagnosis between HD and NHL; that HD is predominantly composed of polyclonal B and T cells; that minor clonal B- or T-cell populations unrelated to RS cells occasionally can be found in HD; and that RS cells do not represent clonal B- or T-cell expansions. Finally, our data preliminarily suggest that RS cells may represent polyclonal T-cell populations.

Adolescent↗

Phosphatidylinositol from ethanol-fed rats confers membrane tolerance to ethanol.

The presence of ethanol disorders (fluidizes) biological membranes, but its chronic administration confers resistance to this perturbation (membrane tolerance). The latter effect has been invoked as an explanation for behavioral tolerance in alcoholics, but the molecular basis for membrane tolerance is obscure. To study the molecular mechanisms of this acquired resistance to disordering, we fed rats ethanol (36% of total calories) for 35 days, after which we quantitatively separated the phospholipids of hepatic microsomal membranes by high-performance liquid chromatography. Multilamellar vesicles were prepared from the recombined phospholipid classes, and their physical properties were examined by electron spin resonance. Vesicles composed of phospholipids from untreated rats were disordered (fluidized) in the presence of ethanol, whereas those made from phospholipids of ethanol-fed rats were resistant to this effect. When phosphatidylcholine (66.5 mol %), phosphatidylethanolamine (21 mol %), or phosphatidylserine (4.0 mol %) from ethanol-fed rats replaced their corresponding phospholipids in vesicles prepared from microsomal phospholipids from untreated rats, the membranes were still disordered by ethanol. In contrast, when 2.5-8.5 mol % phosphatidylinositol from ethanol-fed rats replaced phosphatidylinositol from untreated rats, the reconstituted membranes were rendered resistant to ethanol-induced disordering. Liver microsomal phosphatidylinositol (2.5-8.5 mol %) from ethanol-fed rats also conferred membrane tolerance to vesicles composed of bovine liver and brain phospholipids, an effect which demonstrates that the ability of phosphatidylinositol to confer membrane tolerance is not restricted to the microsomal membrane.

Alcoholism↗

Protein selectivity in IgA nephropathy.

The protein selectivity index was measured in 68 patients (53 males, 15 females) with proteinuria due to IgA nephropathy to determine whether it bore any relationship to other clinical and pathological features of known prognostic significance. The mean age of the patients was 25 +/- 8 years with a follow-up period of 42 +/- 35 months. Forty-six presented with asymptomatic haematuria and proteinuria, 17 with macroscopic haematuria and 5 with the nephrotic syndrome. Twenty-three (34%) patients had selective proteinuria and 45 (66%) had non-selective proteinuria. Patients with non-selective proteinuria had more glomerulosclerosis (29% +/- 20 vs. 16% +/- 20, p less than 0.02), higher serum creatinine (1.47 mg/dl +/- 0.70 vs. 1.17 mg/dl +/- 0.33, p less than 0.02), lower creatinine clearance (79 ml/min +/- 28 vs. 95 ml/min +/- 25, p less than 0.02), and higher incidence of hypertension (chi 2 = 3.84, p less than 0.05) when compared to those with selective proteinuria. The protein selectivity was measured at the end of the study. Of the 5 patients with the nephrotic syndrome, 1 had poorly selective proteinuria and failed to remit and 4 had highly selective proteinuria who either remitted spontaneously (1 patient) or with treatment (3 patients). The results suggest that patients with IgA nephropathy and poorly selective proteinuria are more likely to have other features indicating a poor prognosis such as glomerulosclerosis, renal impairment and hypertension.

Adult↗

Phospholipid spin probes measure the effects of ethanol on the molecular order of liver microsomes.

Ethanol, in vitro, is known to perturb the molecular order of the phospholipids in biological membranes, while chronic ethanol exposure, in vivo, leads to resistance to disordering. Such changes have usually been measured by electron spin resonance, utilizing fatty acid spin probes. The use of such probes is controversial, since their orientation in the membrane may not accurately represent that of individual phospholipids. We, therefore, compared ethanol-induced structural perturbations in the membranes of rat hepatic microsomes measured with the spin probe 12-doxylstearic acid (SA 12) with those assayed with various phospholipid spin probes. With SA 12, the addition of increasing amounts of ethanol (50-250 mM) in vitro caused a progressive decrease in the membrane molecular order, as measured by electron spin resonance (ESR). By contrast, microsomes obtained from rats chronically fed ethanol were resistant to the disordering effect of ethanol. Microsomes labeled with the phospholipid spin probes 1-palmitoyl-2-(12-doxylstearoyl)phosphatidylcholine, -phosphatidylethanolamine, or -phosphatidic acid also exhibited increased disordering with the addition of increasing amounts of ethanol. However, the effect noted with phospholipid spin probes was less than that observed with the fatty acid probe. Microsomes obtained from the livers of chronically intoxicated animals labeled with the phospholipid probes were also resistant to the disordering effects of ethanol in vitro. These results suggest that fatty acid spin probes are qualitatively valid for measuring membrane perturbations in biological membranes, ethanol affects all microsomal phospholipids, regardless of chemical dissimilarities (e.g., head-group structure), in a qualitatively similar fashion, and the fluidization of fatty acyl chains in microsomal membranes is comparable in different membrane phospholipids.

Animals↗

Peak temperature influences on heating rate effect in hyperthermic cytotoxicity.

Exponentially growing Chinese hamster V79 cells were heated from 37 degrees C up to 42 degrees C or 43 degrees C at four different heating rates: immediate exposure, 1/2 hour, 1 hour, and 2 hours. The D0's of the heat survival curves for both 42 degrees C and 43 degrees C were determined for the different heating rates. The results show that the decrease in toxicity to cells at 43 degrees C resulting from a slower heating rate appears to be less pronounced than that at 42 degrees C. However, the thermotolerance ratio is found to depend on the specific heating time (the reciprocal of the heating rate), in a linear fashion and it does not seem to depend on the peak temperature. We propose that the difference in the heat exchange on cell membranes at different rates of heating may contribute to the causes for the difference in cell sensitivity to hyperthermia.

Animals↗