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Biomedical subjects

D Lawrence

Publications and source records attributed to D Lawrence.

At least 73 records · Page 4Linked to original sources
PubMed1994

Human wild type p53 inhibits cell proliferation and elicits dramatic morphological changes in human glioma cell lines in vitro.

A human pilocytic astrocytoma-derived cell line, a grade III astrocytoma-derived cell line, and a glioblastoma-derived cell line were transfected with the human wild-type p53 gene, in order to demonstrate the possible suppressor role of this gene in low grade as well as in high grade human astrocytomas. p53 exhibited a strong growth suppressor effect on the three cell lines studied, irrespective of the grade of malignancy of the tumours from which they originate. Furthermore, the p53 gene elicited important morphological changes in these cell lines. p53-Transfected cells displayed a flat morphology, a large cell body, and a stellate shape with long processes, characteristic of differentiated astrocytes. In addition, the growth inhibitory effect of p53 was found not to be due to induction of apoptosis. These results indicate that p53 plays a tumour suppressor role in low grade and high grade human astrocytomas and raise the possibility of the involvement of p53 in glioma cell differentiation in vitro.

Astrocytoma↗
PubMed1994

Interpreting HIV serodiagnostic test results in the 1990s: social risks of HIV vaccine studies in uninfected volunteers. NIAID AIDS Vaccine Clinical Trials Group.

OBJECTIVE: To evaluate the influence of a human immunodeficiency virus (HIV) vaccine given to uninfected volunteers on the interpretation of serodiagnostic HIV test results. DESIGN: Retrospective cohort study. SETTING: 5 AIDS Vaccine Evaluation Units funded by the National Institute of Allergy and Infectious Diseases. PARTICIPANTS: The first 266 healthy adult volunteers (aged 18 to 60 years) who did not have HIV infection and whose history suggested that they were at low risk for acquiring HIV infection. MEASUREMENTS: HIV antibody was measured by enzyme-linked immunosorbent assay (ELISA) and Western blot test, the results of which were interpreted on the basis of four different published criteria. RESULTS: At some time during the first 12 months of the vaccine studies, 68% of volunteers were positive for HIV antibodies by ELISA. Depending on criteria used to interpret Western blot test results, 0% to 44% of volunteers had positive results that might have caused them to be incorrectly labeled as HIV infected. CONCLUSIONS: Significant social risks to volunteers participating in HIV vaccine studies were identified. Persons interpreting HIV serodiagnostic test results must consider that an HIV vaccine can cause a positive result in persons who are not infected.

AIDS Vaccines↗
PubMed1994

Use effectiveness of the Creighton model ovulation method of natural family planning.

OBJECTIVE: To determine the use effectiveness of the Creighton model ovulation method in avoiding and achieving pregnancy. DESIGN: Prospective, descriptive. SETTING: A natural family planning clinic at a university nursing center. PARTICIPANTS: Records and charts from 242 couples who were taught the Creighton model. The sample represented 1,793 months of use of the model. MAIN OUTCOME MEASURE: Creighton model demographic forms and logbook. RESULTS: At 12 months of use, the Creighton model was 98.8% method effective and 98.0% use effective in avoiding pregnancy. It was 24.4% use effective in achieving pregnancy. The continuation rate for the sample at 12 months of use was 78.0%. CONCLUSION: The Creighton model is an effective method of family planning when used to avoid or achieve pregnancy. However, its effectiveness depends on its being taught by qualified teachers. The effectiveness rate of the Creighton model is based on the assumption that if couples knowingly use the female partner's days of fertility for genital intercourse, they are using the method to achieve pregnancy.

Adult↗
PubMed1994

Hepatic arterial infusion of floxuridine, leucovorin, doxorubicin, and cisplatin for hepatocellular carcinoma: effects of hepatitis B and C viral infection on drug toxicity and patient survival.

PURPOSE: To conduct a pilot trial of hepatic arterial infusion (HAI) of floxuridine (FUDR), leucovorin, Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), and cisplatin (FLAP) in nonresectable hepatocellular cancer (HCC) confined to the liver and assess the effects of hepatitis B (HBV) and hepatitis C (HCV) viral markers on toxicity, response to treatment, and patient survival. PATIENTS AND METHODS: Of 31 HCC patients, 13 were HBV- and HCV-nonreactive, and 18 had evidence of either current or prior HBV and/or HCV infection. Treatment was delivered through percutaneous hepatic arterial catheters, and Infusaid pumps (Shiley Infusaid, Norwood, MA) were placed in responding patients. Cisplatin (100 mg/m2) and Adriamycin (30 to 35 mg/m2) were administered on day 1, followed by a continuous 24-hour HAI of an admixture of floxuridine (60 mg/m2) and leucovorin (15 mg/m2) daily for 4 days. Treatment was repeated every 5 weeks. RESULTS: Twelve (41%) of 29 assessable patients had a partial response (PR), with a median time to disease progression of 13 months. Six (50%) of 12 HBV-negative (HBV-)/HCV-negative (HCV-) and six of 17 (35%) HBV-positive (HCV+) and/or HCV-positive (HCV+) patients achieved a PR. Eight patients have been maintained in remission for a median duration greater than 15.5 months. The median survival duration of all 31 patients was 15 months, 7.5 months among HBV+ and/or HCV+ patients, and significantly longer among hepatitis-non-reactive patients (P = .007). (A median has not yet been reached.) Granulocylopenia (< 0.1 x 10(3)/microL), thrombocytopenia (< 25 x 10(3)/microL), and hospitalizations for infectious complications were significantly more common among HBV-HCV-reactive than -nonreactive patients: 56%, 50%, and 67% versus 15%, 15%, and 8%, respectively (P < .05 for all). CONCLUSION: HAI of FLAP has induced long-term PR and has palliated extensive nonresectable HCC. Positive hepatitis serology appeared to increase bone marrow susceptibility to myelotoxic drugs. Conceivably, one or both viruses may have a direct inhibitory effect on bone marrow progenitors and thereby contribute to the observed myelotoxicity.

Aged↗
PubMed1993

Health status, health perceptions, and health behaviors of young adult women.

A descriptive, exploratory study of 76 young adult women enrolled in a women's health course at a large, midwestern university was undertaken to identify their current health status, health perceptions, and general health behaviors. Two groups of young adult females participated, nursing students (n = 38) and non-nursing students (n = 38). The panel of young adult women in this study reported their health as good or excellent, viewed health as very important and generally used positive health practices. However, data revealed that the lifestyles of many respondents were not conducive to promoting or maintaining health. Negative health practices identified were drinking and driving, non-performance of self breast examinations, ineffective stress management strategies and poor dietary and exercise habits. No significant differences were noted between nursing and non-nursing students.

Adult↗
PubMed1993

Erythrocyte membrane structure in bipolar affective disorder: a non-replication.

Fifteen bipolar patients were compared with sixteen controls in an attempt to replicate the findings of Pettegrew et al. in 1982 of decreased fluidity in the hydrocarbon core of the erythrocyte membrane. No significant differences were seen between groups. The present control group shows very similar membrane characteristics to the original control series; however, the bipolar patient group is not similar. Possible explanations are discussed.

Adult↗
PubMed1993

Nonenzymatic glycosylation of laminin and the laminin peptide CIKVAVS inhibits neurite outgrowth.

Nerve regeneration in diabetic animals is delayed and qualitatively impaired, but the mechanisms responsible for these defects have not been elucidated. The extracellular matrix protein laminin promotes the extension of neuronal processes, and recent studies have localized neurite-promoting activity to a lysine-containing sequence (IKVAV) within the laminin molecule. Because long-lived molecules such as laminin are likely to accumulate excessive amounts of nonenzymatic glycosylation products in diabetic subjects, we have investigated whether such adduct formation on laminin or the IKVAV peptide affects their neurite-promoting properties. These studies used the murine neuroblastoma cell line NB2a, which extends neurites on laminin when differentiated by cAMP. Neurite outgrowth in NB2a cells plated on glycosylated laminin was significantly decreased from that occurring on unmodified laminin. Similarly, neurite outgrowth in NB2a cells plated on glycosylated IKVAV peptide was inhibited compared with that observed on native IKVAV. These data suggest that nonenzymatic glycosylation of a biologically active domain within laminin may contribute to impaired nerve regeneration in diabetes.

Amino Acid Sequence↗
PubMed1993

The CAT-CAM socket and quadrilateral socket: a comparison of energy cost during ambulation.

Twenty unilateral trans-femoral amputees fitted with either the Contoured Adducted Trochanteric-Controlled Alignment Method (CAT-CAM) socket (n = 10) or the quadrilateral (QUAD) socket (n = 10), and a "non-amputee" control group (n = 10) participated in the study. Subjects meeting the following criteria were studied: healthy males between the ages of 18 and 55 years, amputation due to non-vascular pathology, an unaffected sound limb, at least six months use of the test prosthesis, and a minimal stump length of 15 cm. Subjects ambulated in two randomized trials separated by 20 minutes of rest at 2 assigned speeds: a pace reflecting normal walking speed (97 m/min = 2.5 mph) or a slower speed (48.5 m/min = 1.25 mph). Heart rate (HR) and Oxygen uptake (VO2) measured during steady state walking were analyzed via two-way ANOVA. Differences among means were further analyzed using Tukey post hoc and simple effects tests. Significant differences were observed between the control group and CAT-CAM subjects with respect to VO2 (p < 0.05) and HR (p < 0.01) at the slower speed. The control group and subjects using the QUAD socket also differed with respect to VO2 (p < 0.01) and HR (p < 0.01) at the slower pace. Faster pace required more energy expenditure (p < 0.01) and produced higher HR (p < 0.01) than slower speeds. At faster pace, a significantly higher energy expenditure in the QUAD than the CAT-CAM group was observed (p < 0.01). It is concluded that ambulating at normal pace using the CAT-CAM socket design uses less energy than when using a QUAD socket design.

Adolescent↗
PubMed1992

Results of surgical management of portosystemic shunts in dogs: 20 cases (1985-1990).

Serum bile acid (SBA) values were obtained in 20 dogs, 2.5 to 60 months (mean, 18.6 months) after surgery for occlusion of a congenital portosystemic shunt. The SBA values obtained after food was withheld were significantly (P < 0.005) reduced at follow-up, compared with preoperative values. In 85% of the dogs (17/20), response to surgery was graded by the owners as excellent or good, although most dogs had abnormal SBA values at follow-up. Significant difference in clinical results or follow-up SBA values was not found in dogs that had complete or partial occlusion of the shunting vessel. Correlation between clinical results and SBA values also was not detected. Dogs that were > 2 years old at the time of diagnosis and surgery had a significantly (P = 0.012) poorer clinical result than that of dogs < 1 year old.

Animals↗
PubMed1992

Growth in serum-free medium of NIH3T3 cells transformed by the EJ-H-ras oncogene: evidence for multiple autocrine growth factors.

Rodent fibroblastic cells transformed by ras oncogenes can grow in serum-free (S-) medium. We have studied clonal lines of mouse NIH3T3 fibroblasts transfected with the EJ-H-ras oncogene, and observed that practically all become independent of exogenous growth and attachment factors shortly after transfection. Moreover, all the clones tested soon form anchorage-independent (AI) colonies in S- medium, and most give rise to spheroids able to grow in suspension. The cell-conditioned S- medium of the transformed (TR) cells stimulates autocrinally the AI and anchored growth of these cells, in the absence of serum, and it contains growth factors related to TGF-alpha (or EGF), PDGF and bFGF, and other uncharacterized factors. Some of these factors are not found, or are found only in very small amounts, in the S- medium of non-transformed NIH3T3 cells, which also stimulates the growth of the TR cells, in the absence of serum. In addition, the TR cells contain 4-6 times more cell-associated bFGF than the non-transformed cells and release more latent TGF-beta activatable by acid treatments. However, no active TGF-beta is secreted by either cell type. Activated TGF-beta and pure TGF-beta 1 stimulate the growth of the anchored TR and NIH3T3 cells, but inhibit the AI growth of the TR cells. Another inhibitor of this growth is also found in the concentrated medium of the NIH3T3 cells.

3T3 Cells↗
PubMed1992

Morphologic characteristics of acute lymphoblastic leukemia (ALL) with abnormalities of chromosome 8, band q24.

The CALGB prospectively studied 140 adult acute lymphoblastic leukemia (ALL) patients for cytogenetic abnormalities. Seven (5%) patients with adequate cytogenetic preparations had t(8;14)(q24;q32) or t(8;22)(q24;q11). Patients were compared with non-8q24 patients for clinical and laboratory characteristics, response to therapy, and survival. The median age of patients with translocations involving 8q24 (71% males) was 40 years. Forty-three percent had lymphadenopathy, 29% splenomegaly, and 29% hepatomegaly. None exhibited central nervous system (CNS), skin, or gum involvement. These features did not differ significantly from non-8q24 ALLs. Patients with 8q24 translocations had higher hemoglobins (11.5 vs. 9.8 g/dl; P = 0.04) and lower percentage of blasts in the peripheral blood (8.5% vs. 69%; P = 0.007). Although all seven were finally categorized as ALL-L3, a marked variation in the proportion of typical L3 blasts was observed that initially resulted in the diagnoses of ALL-L2 in three cases and prolymphocytic leukemia in one. In five of five patients, the blasts typed as B cells (SIg+ and CD19+). Complete remission rates for patients with 8q24 translocations were 43%, whereas they were 68% for non-8q24 ALLS (P = 0.22). Furthermore, patients with 8q24 abnormalities exhibited significantly shorter survival (4.8 vs. 18.4 mo; P less than 0.001). We conclude that ALL with translocations of 8q24 in adults shows a mature B-cell immunophenotype (SIg+), poor prognosis and morphology ranging from classical ALL-L3 to ALL with a subpopulation of L3 cells. Thus, the diagnosis of ALL-L3 should be made when blastic cells possess a mature B-cell immunophenotype (SIg+) and an 8q24 translocation, even though the number of L3 cells is low.

Adult↗
PubMed1992

Distribution of beta-adrenergic receptor subtypes in human post-mortem brain: alterations in limbic regions of schizophrenics.

The distribution of the beta 1 (beta 1) and beta 2 (beta 2) subtypes of the beta-adrenergic receptor was examined in rat and nondiseased control human tissue. The distribution of the beta 1 and beta 2 receptors was also examined in schizophrenic cases, with additional studies in schizophrenic suicide and nonschizophrenic suicide cases. Scatchard analysis of the binding of [125I]iodopindolol (IPIN) to cortical membranes showed a similar Kd in human (177 pM) and rat (161 pM), but a lower maximum binding site (Bmax) in the human tissue (18.7 fmol/mg protein and 55.6 fmol/mg protein). For the autoradiographic studies [125I]IPIN was used to visualize both subtypes (total) or was displaced with the selective beta 1-receptor antagonist ICI-89,406 to visualize beta 2 sites, or with the selective beta 2-receptor antagonist ICI-118,551 to visualize beta 1 sites. Important differences in the regional distribution of the two subtypes of the beta-adrenergic receptors were noted between rat and human. In the nucleus accumbens and ventral putamen (ventral striatum), a patchy distribution of beta 1 receptors was observed that was not evident in the rat. These patches were aligned with markers of the matrix compartment of the striatum. The schizophrenic cases showed significant increases in the labeling of the beta 1-receptor patches with [125I]IPIN. In contrast to the frontal cortex of the nondisease controls, the parietal and temporal cortex showed a high ratio of beta 1 to beta 2 receptors and a highly laminar organization of the subtypes. [125I]IPIN binding to beta 1 receptors was highest in the external laminae with the reverse gradient for the beta 2 subtype. The medial temporal cortex displayed an alteration in the ratio of the 2 subtypes of the beta-adrenergic receptor, with the parahippocampus and hippocampus of the human, in contrast to the rat brain, predominantly expressing the beta 2 receptor. Moreover, there were consistently higher densities of beta 2 receptors in the hippocampus of the right hemisphere than the left hemisphere of the nondisease controls. There was not a left and right hemispheric asymmetry of beta 2 receptors in the hippocampus of elderly schizophrenics or in young schizophrenics who committed suicide. The asymmetry was evident in nonschizophrenic suicides, suggesting that the lack of asymmetry in the hippocampus of schizophrenics is evident early in the disease process. Thus limbic structures show alterations in the patterning of beta 1 and beta 2 receptors in the schizophrenic cases.

Adult↗
PubMed1992

Regulation of adrenal atrial natriuretic hormone receptor subtypes.

Regulation of atrial natriuretic hormone (ANH) receptor binding and aldosterone suppression was studied in isolated adrenal glomerulosa cells from rats fed a high-salt (HS) or low-salt (LS) diet for 3 days. In plasma of HS rats, aldosterone levels were 5 times lower and immunoreactive ANH two times higher than in LS rats. Competitive binding studies showed the same affinity for human atrial natriuretic hormone (hANH) in both pools of cells, but receptor density was 50% higher on LS cells. A linear ANH analog that binds to non-guanylate-cyclase-coupled receptors did not show increased binding to LS cells. Cyclic GMP production in response to hANH was identical in both groups. The aldosterone-inhibitory effect of hANH on both groups of basal and angiotensin II-stimulated cells was also identical. Thus a short-term high-salt diet causes decreased density of ANH receptors in glomerulosa cells without changing biological activity of ANH. These results suggest that dietary salt content changes the number of ANH receptors and that non-guanylate-cyclase-coupled receptors contain at least two classes of receptors.

Aldosterone↗
PubMed1992

Human immunodeficiency virus infection due to clotting factor concentrates: results of the Seroconversion Surveillance Project.

From 1987 to the present, the Seroconversion Surveillance Project has provided the means by which to monitor the risk of transmission of human immunodeficiency virus (HIV) by clotting factor concentrates. One hundred thirty-one hemophilia treatment centers in the United States are contacted regularly, and data on HIV testing of patients are collected. To date, 4366 (46.0%) of 9496 patients have been reported to be seropositive, and 37 new seroconversions have been identified. Nine of these have met the Centers for Disease Control criteria for seroconversion while the patient was taking factor concentrate. None of the nine seroconversions were due to concentrates that had been treated to inactivate viruses and made from plasma that had been tested for HIV antibody. These results indicate that there is a high prevalence of seropositivity in affected patient groups, but that the risk of HIV infection from currently available clotting factor concentrates is extremely low.

Blood Coagulation Disorders↗