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Biomedical subjects

B Patterson

Publications and source records attributed to B Patterson.

At least 37 records · Page 2Linked to original sources

Immature human cord blood progenitors engraft and proliferate to high levels in severe combined immunodeficient mice.

Unseparated or Ficoll-Hypaque (Pharmacia, Piscataway, NJ)--fractionated human cord blood cells were transplanted into sublethally irradiated severe combined immunodeficient (SCID) mice. High levels of multilineage engraftment, including myeloid and lymphoid lineages, were obtained with 80% of the donor samples as assessed by DNA analysis, fluorescence-activated cell sorting (FACS), and morphology. In contrast to previous and concurrent studies with adult human bone marrow (BM), treatment with human cytokines was not required to establish high-level human cell engraftment, suggesting that neonatal cells either respond differently to the murine microenvironment or they provide their own cytokines in a paracrine fashion. Committed and multipotential myelo-erythroid progenitors were detected using in vitro colony assays and FACS analysis of the murine BM showed the presence of immature CD34+ cells. In addition, human hematopoiesis was maintained for at least 14 weeks providing further evidence that immature hematopoietic precursors had engrafted the murine BM. This in vivo model for human cord blood-derived hematopoiesis will be useful to gain new insights into the biology of neonatal hematopoietic cells and to evaluate their role in gene therapy. There is growing evidence that there are ontogeny-related changes in immature human hematopoietic cells, and therefore, the animal models we have developed for adult and neonatal human hematopoiesis provide useful tools to evaluate these changes in vivo.

Animals

Acinic cell carcinoma of salivary glands. Prognostic relevance of DNA flow cytometry and nucleolar organizer regions.

OBJECTIVE: To test the prognostic ability of flow cytometry and counts of silver-enhanced intranuclear nucleolar organizing regions (AgNORs) in acinic cell carcinoma. DESIGN: Using statistical methods to establish if analysis of DNA content, percentage DNA synthetic (S)-phase, and the AgNOR counts on 45 cases of acinic cell carcinoma with clinical follow-up ranging from 10 to 379 months are predictors of time to recurrence or time to death due to acinic cell carcinomas. MAIN OUTCOME MEASURES: Whether tumors with low AgNOR counts and diploid DNA are favorable acinic cell carcinomas and the converse, aneuploid DNA and elevated AgNOR count, predict unfavorable neoplasms. RESULTS: Tumors with a diploid DNA content had as unfavorable a clinical course as aneuploid acinic cell carcinomas. Similarly, S-phase and AgNOR count results showed considerable overlap when separated into carcinomas with or without local recurrence, metastasis, or death due to tumor. Statistical evaluation also failed to provide predictors of clinical course based on ploidy, percentage S-phase, or AgNOR counts. CONCLUSION: The results, although negative, are important in showing that data on DNA content, cell cycle, and nuclear limits useful in other neoplasms are of limited practical application in establishing predictors of time to recurrence or time to death in acinic cell carcinomas. Solving the enigmas, for clinicians and pathologists, associated with acinic cell carcinomas will require further information about the biology of this neoplasm.

Adult

Risk taking and its influence on metabolic control: a study of adult clients with diabetes.

Clients afflicted with diabetes are routinely faced with making decisions about insulin control, diet, exercise and skin care. The specific aims of this study were (a) to determine if clients with controlled blood sugar levels were more likely to have risk-averse information processing styles and, (b) to determine the extent to which the differences in blood sugar levels were attributed to information processing styles, after controlling for knowledge of diabetes, participation in home monitoring, and age. A comparative design utilizing 86 insulin-dependent male and female clients with diabetes was used. Findings indicated that there were no differences in risk scores between uncontrolled and controlled diabetics. Additionally, in this study there were no differences in control between clients who were knowledgeable and those who were not. This study has several implications for nursing practice. As taking risks may not be as dangerous to the diabetic client's wellbeing as many believe, there may be a need to consider this behaviour in developing the client's plan of care. Questions are also raised about the influence of knowledge on control.

Adult

Stage-specific requirement for myosin II during Dictyostelium development.

Dictyostelium cells that lack a functional myosin II heavy chain are motile and are capable of aggregation, but fail to undergo further multicellular development. We have used a Dictyostelium mutant expressing a cold-sensitive myosin heavy chain to examine the requirement for myosin throughout the course of development. The loss of myosin function upon cooling is rapid and reversible. Temperature-shift experiments reveal that myosin is essential during two different stages of development. During aggregation, myosin function appears to be necessary for cells to sort correctly in a way that allows further development to occur. During the final stage of development, it is required for the formation of a complete stalk and the raising of the spore head. Development between those stages, however, proceeds normally in the absence of myosin function. Aggregates at non-permissive temperature undergo an aberrant form of development resulting in a ball of cells. Calcofluor staining and reporter gene fusions reveal that these structures contain defective spores and a miniature stalk.

Animals

"Eat for Health": a supermarket intervention for nutrition and cancer risk reduction.

OBJECTIVES: The results of an evaluation of "Eat for Health," a supermarket nutrition intervention, are presented. The study tested whether such a program could be successfully carried out and whether it could effect changes in knowledge, attitudes, and food purchasing behavior in line with nutrition and cancer risk reduction guidelines. METHODS: The evaluation consisted of an in-store monitoring element, an in-store and telephone consumer survey, and an analysis of sales data on selected foods. A matched-pair design, using a total of 40 stores in the intervention and comparison groups, was used. RESULTS: The intervention was successfully implemented and had limited success in changing some food purchasing behaviors. There appeared to be no effect on knowledge and attitudes except for increased awareness of a link between diet and cancer and of the program itself. CONCLUSIONS: Despite the intervention's success, limitations of the consumer survey and sales data analyses and the continuing diffusion of nutrition messages throughout society make it difficult to specify the impact of this program on consumer nutrition knowledge and behaviors.

Adult

SCID mice as an in vivo model of human cord blood hematopoiesis.

Cord blood is increasingly used as an alternative stem cell source for autologous and allogeneic transplantation, particularly in pediatric patients. We therefore adopted our protocol for transplanting human adult bone marrow cells into severe combined immunodeficient (SCID) mice [1] to develop an in vivo model for cord blood hematopoiesis. Intravenous injection of unfractionated or Ficoll-separated cord blood cells into sublethally irradiated SCID mice led to high levels of human hematopoiesis in the majority of the recipients [2]. Multilineage human hematopoiesis including committed and multipotential myeloerythroid progenitors as well as CD19+ B-lymphoid cells were observed in the murine bone marrow for at least 18 weeks. Together, these data indicate that the SCID mice were engrafted with an immature cell that was able to maintain multiple progenitor lineages in vivo. In contrast to our experiences with adult bone marrow, high levels of human cell engraftment in the mouse could be achieved without exogenous cytokine treatment, suggesting that the cord blood cells respond differently to the murine microenvironment. Alternatively, the cord blood cells might have been able to provide themselves with the necessary growth factors in a paracrine fashion. This model will be useful in gaining new insights into the biology of immature human cord blood progenitors and cord blood transplantation.

Animals

Pneumatosis intestinalis with free air mimicking intestinal perforation in a bone marrow transplant patient.

A case of pneumatosis intestinalis with perforation is reported in a patient after bone marrow allograft for chronic myeloid leukemia. Risk factors included the transplant, prolonged immunosuppression and neutropenia, graft-versus-host disease, extended use of corticosteroids, infection and lower gastrointestinal endoscopic biopsy. The literature is reviewed and a management plan for patients presenting with this complication is discussed.

Adult

A hematopoietic protein tyrosine phosphatase (HePTP) gene that is amplified and overexpressed in myeloid malignancies maps to chromosome 1q32.1.

Tyrosine phosphorylation is an important regulator of cell growth and differentiation reflecting the interaction of protein tyrosine kinases (PTK) and protein tyrosine phosphatases (PTP). Although excessive PTK activity can result in hematopoietic cell transformation, perturbation of either of these two modulators may result in uncontrolled cell growth. Myeloid cells are responsive to growth factors and cytokines that induce tyrosine phosphorylation and can become ligand independent when endogenous PTKs become dysregulated. Specific PTPs, through mutation or altered expression, may enhance PTK activities and also cause myeloid ligand independence, though this has not yet been demonstrated. We have previously reported the isolation of a hematopoietic specific cytoplasmic PTP (HePTP). We now report that this gene maps to chromosome 1q32.1 utilizing fluorescent in situ chromosomal hybridization (FISH). This site is frequently amplified in preleukemic myeloproliferative diseases. FISH analysis of a patient with myelodysplastic syndrome characterized by myeloid hypoplasia and monocytosis reveals triplication of the HePTP gene on one allele with elevated protein expression in neoplastic myelomonocytic cells. Elevated expression is also identified in blasts from some patients with acute leukemia. These observations prompted us to examine the experimental effects on cell growth of HePTP overexpression. Though normal myeloid cells show minimal HePTP expression, all hematopoietic cell lines tested show high expression of HePTP. Gene transfer of HePTP into NIH 3T3 cells was therefore performed, which caused altered cell morphology, disorganized growth, anchorage independent colony formation and subtle differences in the pattern of tyrosine phosphoproteins compared to control cell lines. We conclude that amplification and overexpression of HePTP may be an important cofactor contributing to abnormal myeloid cell growth.

Adult

Zygotic transcription and cell proliferation during Drosophila embryogenesis.

The zygotic expression of only a few Drosophila genes is known to be required for completion of the normal embryonic mitoses. Molecular genetic analyses of these genes reveal that they fall into two classes, those whose mRNA levels are regulated in a stage and/or tissue-specific fashion to control cell cycle events during embryogenesis, and those in which, in the absence of functional zygotic expression, the maternal mRNA contribution does not provide sufficient product to complete the normal embryonic mitoses. Genes that comprise the first class are involved in the developmental control of the cell cycle, while those of the second class identify components of the cell cycle machinery.

Animals

Engraftment of human lymphoid cells into newborn SCID mice leads to graft-versus-host disease.

Although there has been considerable progress in transplanting normal human hematopoietic cells into immune-deficient mice, the establishment of a functional human immune system has proved to be difficult. Current methods of introducing mature human lymphoid cells into adult SCID mice lead to oligoclonal engraftment with restricted dissemination to various organs. We have attempted to improve human lymphoid cell engraftment in mice, both qualitatively and quantitatively, by injecting human bone marrow cells and peripheral blood leukocytes intraperitoneally into newborn SCID mice. Newborn mice were used as recipients because certain immune functions such as natural killer cell activity do not develop until several weeks after birth and the numerous growth factors secreted in young mice may facilitate the engraftment and proliferation of transplanted human cells. At various times after transplantation, the presence of human cells in different organs was determined by Southern blot analysis using a human specific probe. Within 4 weeks, 70% of the mice were engrafted with human cells. Human cell engraftment of the bone marrow, spleen, lungs, kidneys, liver, and thymus exceeded 10% in at least 40% of the transplanted mice; most of these highly engrafted mice were sick. Flow cytometry and immunocytochemistry indicated these organs were heavily infiltrated with mature T and B lymphocytes. Histologic and molecular analysis showed massive human cell infiltrates within the liver, lung and spleen. The presence of human IgG and IgM antibodies against mouse red blood cells provided evidence that the engrafted human cells retained some immune function. Mice transplanted with peripheral blood leukocytes from donors that were allergic to mouse antigens engrafted to the same extent as normal cells but in addition developed the classical symptoms of acute allogeneic graft-versus-host disease (GVHD) including infiltrates of the skin, gut, and liver. The newborn SCID system provides a new in vivo model to study human xenoreactivity and GVHD.

Animals

Neurologic prognosis of cytomegalovirus polyradiculomyelopathy in AIDS.

Cytomegalovirus (CMV) polyradiculomyelopathy is an uncommon but distinctive clinical syndrome in HIV-infected patients in which ascending motor weakness, areflexia, loss of sphincter control, paresthesias, and varying sensory impairment develop subacutely in association with a polymorphonuclear pleocytosis, increased protein, and hypoglycorrhachia in CSF. Responses to treatment with ganciclovir have varied in reported cases. We report three additional cases: two of these patients responded to treatment and the third was demonstrated to have CMV resistant to ganciclovir. We review other reported cases and identify factors predictive of ganciclovir resistance, which include persistent polymorphonuclear pleocytosis and hypoglycorrhachia on serial CSF studies, and positive CMV cultures from CSF or blood after induction therapy. We conclude that ganciclovir may be an effective therapy for CMV polyradiculomyelopathy, but the presence of these factors, or the development of the syndrome in a patient already being treated with ganciclovir, should prompt consideration of alternative antiviral therapy.

AIDS-Related Opportunistic Infections

A preliminary study of the relationship between central auditory processing disorder and attention deficit disorder.

Fifteen boys aged six to ten who met the criteria for attention deficit disorder (ADD) were compared with ten boys who did not have ADD in a double-blind, placebo-controlled, single-crossover study of methylphenidate. To assess the degree of overlap between ADD and central auditory processing disorder (CAPD), all subjects were assessed on parent and teacher behavior rating scales, as well as a battery of CAPD tests at baseline and after three and six weeks of treatment. Twelve of the 15 subjects with ADD and none of the subjects without ADD met the criteria for CAPD. The subjects with ADD also responded to stimulant treatment on the measures of both ADD and CAPD. The overlap in the symptomatology of these disorders, the finding that the criteria for both disorders were met in 12 of 15 cases and the sensitivity of both ADD and CAPD measures to treatment with methylphenidate suggest that ADD and CAPD are closely related disorders. The implications of these results are three-fold. First, sustained attention is a critical feature of performance on CAPD tests and the current diagnostic criteria for CAPD make a clinical separation of the two disorders problematic. Second, stimulants appear to be a useful treatment for the symptoms of both ADD and CAPD. Third, CAPD tests may be a useful measure of ADD symptomatology and response to stimulants.

Analysis of Variance

Fruit, vegetables, and cancer prevention: a review of the epidemiological evidence.

Approximately 200 studies that examined the relationship between fruit and vegetable intake and cancers of the lung, colon, breast, cervix, esophagus, oral cavity, stomach, bladder, pancreas, and ovary are reviewed. A statistically significant protective effect of fruit and vegetable consumption was found in 128 of 156 dietary studies in which results were expressed in terms of relative risk. For most cancer sites, persons with low fruit and vegetable intake (at least the lower one-fourth of the population) experience about twice the risk of cancer compared with those with high intake, even after control for potentially confounding factors. For lung cancer, significant protection was found in 24 of 25 studies after control for smoking in most instances. Fruits, in particular, were significantly protective in cancers of the esophagus, oral cavity, and larynx, for which 28 of 29 studies were significant. Strong evidence of a protective effect of fruit and vegetable consumption was seen in cancers of the pancreas and stomach (26 of 30 studies), as well as in colorectal and bladder cancers (23 of 38 studies). For cancers of the cervix, ovary, and endometrium, a significant protective effect was shown in 11 of 13 studies, and for breast cancer a protective effect was found to be strong and consistent in a meta analysis. It would appear that major public health benefits could be achieved by substantially increasing consumption of these foods.

Diet Surveys

Osseous expansion of the cranial vault by craniotasis.

A study of cranial vault lengthening using a custom expandable fixation-distraction (craniotatic) appliance was performed in the young-adult rabbit model. Ten 24-week-old rabbits underwent circumferential suturectomy plus expansion (expanded group), 10 underwent circumferential suturectomy without expansion (sham control group), and 10 served as normal controls. The appliance was lengthened at a rate of 2.5 mm per week for 5 weeks. Serial lateral cephalometry, comparative dry-skull anthropometric measurements, and histologic examinations were performed. The expanded group demonstrated a significantly longer skull, cranial vault, anterior cranial base, posterior face, and orbit as compared with the control groups (p less than 0.05). Callus bone filled the distracted suturectomy and united the frontofacial complex to the posterior cranium. In conclusion, skull lengthening by distraction osteogenesis is possible in the rabbit model and offers a new technique for future investigation in the treatment of coronal synostosis.

Analysis of Variance

Synthetic lethal mutations suggest interactions between U5 small nuclear RNA and four proteins required for the second step of splicing.

To investigate the function of the U5 small nuclear ribonucleoprotein (snRNP) in pre-mRNA splicing, we have screened for factors that genetically interact with Saccharomyces cerevisiae U5 snRNA. We isolated trans-acting mutations that exacerbate the phenotypes of conditional alleles of the U5 snRNA and named these genes SLU, for synergistically lethal with U5 snRNA. SLU1 and SLU2 are essential for the first catalytic step of splicing, while SLU7 and SLU4 (an allele of PRP17 [U. Vijayraghavan, M. Company, and J. Abelson, Genes Dev. 3:1206-1216, 1989]) are required only for the second step of splicing. Furthermore, slu4-1 and slu7-1 are lethal in combination with mutations in PRP16 and PRP18, which also function in the second step, but not with mutations in factors required for the first catalytic step, such as PRP8 and PRP4. We infer from these data that SLU4, SLU7, PRP18, PRP16, and the U5 snRNA interact functionally and that a major role of the U5 snRNP is to coordinate a set of factors that are required for the completion of the second catalytic step of splicing.

Base Sequence

Growth of human lymphoma cells in SCID mice.

Two EBV-negative human lymphoma cell lines raised in this laboratory and peripheral blood cells of a patient with large cell lymphoma in leukemic phase were injected intravenously or intraperitoneally into C.B.17 SCID mice. One line (OCI-LY18) was derived from the pleural fluid of a patient with a large cell, immunoblastic malignant lymphoma. Cells of this line are of B cell origin and characterized by multiple rearrangements of the JH locus. The second line (OCI-LY17) was grown from the peripheral blood of a patient with a large cell lymphoma of T-cell phenotype which has characteristic rearrangement of the T-cell receptor beta chain. The cells directly obtained from a patient with large cell non-cleaved malignant lymphoma were of B-cell origin. Animals carrying OCI-LY18 developed large tumor masses within 6-8 weeks of inoculation. The tumors were detected in the intestine, mesentery, retroperitoneum, lymph nodes, spleen, lung and kidney. The masses resembled the primary tumor with respect to histological appearance and immunological phenotype. It was possible to generate secondary cell lines from the tumors found in the inoculated SCID mice. Injection of one of these secondary cell lines into SCID mice resulted in the rapid development of lymphoma and as few as 10 cells were sufficient to establish the disease in the inoculated animals. In contrast cells of OCI-LY17 produced small tumor aggregates that did not appear to progress over time and did not cause death of the animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Surrogate decision-maker preferences for medical care of severely demented nursing home patients.

BACKGROUND: In the absence of advanced directives, physicians treating demented patients rely on surrogates to help make medical care decisions. METHOD: We surveyed family members of severely demented nursing home residents to determine preferences for medical intervention in five hypothetical situations involving tube feeding, hospitalization, intensive care unit admission, mechanical ventilation, and cardiopulmonary resuscitation. RESULTS: Only 11.8% of surrogates rejected all interventions. Cardiopulmonary resuscitation and tube feeding were accepted least frequently (31.6% and 36.4%, respectively). Mechanical ventilation, hospitalization, and intensive care unit admission were accepted by 43.6%, 63.4%, and 75.2%, respectively. There was no correlation between previous surrogate experience with an intervention and its acceptance. Nearly 70% of surrogates indicated that decisions were independent of any previously expressed resident views. CONCLUSIONS: In this study, surrogates of even the most demented nursing home patients prefer hospital level services including intensive care unit care for the treatment of acute illness. Efforts to control access to services on ethical or economic grounds may meet with resistance.

Aged