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Biomedical subjects

E Richie

Publications and source records attributed to E Richie.

18 recordsLinked to original sources

Safety and immunogenicity of combined diphtheria-tetanus-pertussis (whole cell and acellular)-Haemophilus influenzae-b conjugate vaccines administered to Indonesian children.

A randomized double-blind trial was conducted to evaluate the safety and immunogenicity of vaccines comprised of diphtheria (D) and tetanus (T) toxoids combined with either a whole cell (P) or an acellular (aP) pertussis component and Haemophilus influenzae type b polyribosylphosphate (PRP) tetanus toxoid conjugate (PRP-T) in Indonesian infants. Three doses of either DTaP, DTaP-PRP-T, or DTP-PRP-T were administered to 930 infants approximately 2-3 months of age and at 2 month intervals thereafter. A booster dose of either DTP-PRP-T or DTaP-PRP-T was administered at 15-18 months of age. Both local and systemic reactions occurred at a significantly (p < 0.001-0.026) higher rate in the group that received whole cell pertussis vaccine versus groups which were immunized with aP containing vaccines. There was no significant difference (p > 0.05) in the rate of adverse events between groups immunized with DTaP or DTaP PRP T. One month after the third dose of vaccine, 99% of subjects had achieved > or =0.1 IU of anti-D and anti-T antibody per ml of serum. The geometric mean titer (GMT) to D was significantly (p < 0.001) higher in the group immunized with DTaP versus the other two groups whereas the anti-T GMT was significantly (p < 0.006) higher for the group immunized with DTP-PRP-T. Both the anti-pertussis toxin (PT) and anti-filamentous hemagglutinin (FHA) antibody levels were significantly (p < 0.001) higher in recipients of acellular versus whole cell pertussis vaccine. In contrast, the anti-B. pertussis agglutinating antibody response was significantly (p < 0.0001) higher in the group immunized with whole cell pertussis vaccine. The anti-PRP GMTs (microg antibody/ml) at 7 months were 0.096, 3.35 and 6.11 for groups immunized with DTaP, DTaP-PRP-T and DTP-PRP-T, respectively. The GMT for those immunized with DTP-PRP-T was significantly (p < 0.001) higher compared to recipients of DTaP-PRP-T. The percent of children who attained > or =0.15 or > or =1 microg/ml after immunization was 18 and 2% for the DTaP group, 93 and 76% for the DTaP-PRP-T group and 97 and 88% for the DTP-PRP-T group. At the > or =1 microg/ml level the difference between the DTaP-PRP0-T and DTP-PRP-T groups was significant (p < 0.01). Children immunized with either DTaP, DTaP-PRP-T, or DTP-PRP-T were reimmunized with DTaP-PRP-T whereas a portion of children immunized with DTP PRP T where also boosted with this vaccine at 15-18 months of age. There was a vigorous anamnestic response to the D and T components with all children possessing > or =0.1 IU/ml. There was also a substantial increase in anti-PT, anti-FHA and B. pertussis agglutinating antibodies. The poorest anti-PT response was seen among children receiving DTP-PRP-T for both primary and reimmunization while the highest agglutinating antibody response followed receipt of 4 doses of DTP-PRP-T. Greater than 80% of children immunized with either DTP PRP T or DTaP-PRP-T possessed > or =0.15 microg/ml before boosting versus 38% for those vaccinated with DTaP (p < 0.001). Primary immunization with DTP-PRP-T resulted in a significantly (p < 0.05) higher percentage (72%) maintaining > or =1 microg/ml compared to those immunized with DTaP-PRP-T (46%). Prior to reimmunization, the anti-PRP GMT was significantly (p < 0.005) higher for children immunized with 3 doses of DTP-PRP-T versus DTaP-PRP-T. Subsequent to reimmunization, > or =95% of subjects attained > or =1 microg/ml.

Antibodies, Bacterial

Comparison of direct-plating and enrichment methods for isolation of Vibrio cholerae from diarrhea patients.

A direct-plating method on thiosulfate citrate bile salts sucrose agar (DIR-TCBS) in conjunction with enrichment in alkaline peptone water (APW) incubated for both 6 h and 24 h followed by subculture onto TCBS (APW6h-TCBS and APW24h-TCBS, respectively) was performed on 16,034 rectal swab samples for isolating Vibrio cholerae. A total of 2,932 (18.3%) rectal swab samples were positive for V. cholerae O1 biotype El Tor, with the Ogawa serotype constituting 99.2% of the isolates. There were no significant differences in V. cholerae O1 isolation rates between the three culture systems nor between the combinations of any two systems. However, direct plating plus enrichment demonstrated a significantly higher V. cholerae O1 isolation rate than DIR-TCBS alone (P < 0.02). Conversely, enrichment procedure, alone or in combination with DIR-TCBS, yielded significantly more (P < 0.0001) V. cholerae non-O1 isolates than DIR-TCBS alone. The length of incubation time of the enrichment broth, 6 h, offers no significant advantages over 24 h for the isolation of V. cholerae O1 and non-O1. A 24-h enrichment broth incubation period has the practical advantage of being easy to integrate into a normal laboratory workday, whereas 6-h broth enrichment, although more commonly recommended, requires that arrangements be made for after-hours subculture.

Bacterial Typing Techniques

Enterotoxigenic Escherichia coli diarrhea among young children in Jakarta, Indonesia.

The incidence of diarrhea and enterotoxigenic Escherichia coli (ETEC) infection was evaluated in children six months to five years of age from an urban community in Jakarta, Indonesia. From January through May 1994, 408 children were monitored in their homes for diarrheal disease. Thirty-six percent (148 of 408) of the study children had at least one episode of diarrhea during the study period. Twenty-nine (19.6%) of the 148 children with diarrhea had ETEC isolated from a rectal swab sample at least once during the surveillance period; five children had ETEC isolated from two distinct episodes of diarrhea, giving a total of 34 episodes of ETEC positive diarrhea in the study group. Ten of 34 episodes were associated with heat-labile toxin, 15 of 34 with heat-stable toxin, and seven of 34 with both toxins. The mean age of children with diarrhea (1.7 years), whether ETEC positive or negative, was significantly lower than those who did not have diarrhea (2.4 years) during the study period; 82% of the children with ETEC were less than two years of age. This study demonstrates a high incidence of ETEC diarrhea among young children in Jakarta, and suggests this site would be suitable for ETEC vaccine efficacy trials.

Age Distribution

Expression of cyclin D1 in epithelial tissues of transgenic mice results in epidermal hyperproliferation and severe thymic hyperplasia.

To study the involvement of cyclin D1 in epithelial growth and differentiation and its putative role as an oncogene in skin, transgenic mice were developed carrying the human cyclin D1 gene driven by a bovine keratin 5 promoter. As expected, all squamous epithelia including skin, oral mucosa, trachea, vaginal epithelium, and the epithelial compartment of the thymus expressed aberrant levels of cyclin D1. The rate of epidermal proliferation increased dramatically in transgenic mice, which also showed basal cell hyperplasia. However, epidermal differentiation was unaffected, as shown by normal growth arrest of newborn primary keratinocytes in response to high extracellular calcium. Moreover, an unexpected phenotype was observed in the thymus. Transgenic mice developed a severe thymic hyperplasia that caused premature death due to cardio-respiratory failure within 4 months of age. By 14 weeks, the thymi of transgenic mice increased in weight up to 40-fold, representing 10% of total body weight. The hyperplastic thymi had normal histology revealing a well-differentiated cortex and medulla, which supported an apparently normal T-cell developmental program based on the distribution of thymocyte subsets. These results suggest that proliferation and differentiation of epithelial cells are under independent genetic controls in these organs and that cyclin D1 can modulate epithelial proliferation without altering the initiation of differentiation programs. No spontaneous development of epithelial tumors or thymic lymphomas was perceived in transgenic mice during their first 8 months of life, although they continue under observation. This model provides in vivo evidence of the action of cyclin D1 as a pure mediator of proliferation in epithelial cells.

Aging

Influence of sex and carcinogen treatment protocol on tumor latency and frequency of K-ras mutations in N-methyl-N-nitrosourea-induced lymphomas.

N-methyl-N-nitrosourea (MNU) induces thymic lymphomas in AKR mice after a 2-3 month latency. This study shows that hormonal factors profoundly influence MNU-induced lymphomagenesis. Tumor development is accelerated in females compared to males, regardless of whether a single high dose or multiple low doses of MNU are administered. Testosterone is implicated in this phenomenon, since castrated mice develop MNU-induced lymphomas with the same latency as intact females, while ovariectomized females have the same pattern of tumor development as intact females. Furthermore, reconstitution experiments demonstrated that testosterone replacement suppresses MNU-induced lymphoma development in castrated males. Although tumor development is delayed in male compared to female mice, sex does not influence tumor immunophenotype, clonality or the frequency of ras mutations in animals given identical MNU treatment protocols. In contrast, the frequency of ras mutations is dramatically altered depending on whether the animals are treated with a single high dose or multiple low doses of MNU. Nevertheless, there is no correlation between the presence of an activated K-ras allele and tumor latency. These data demonstrate that sex has a more profound influence on the progression of MNU-induced lymphomas than does the presence of an activated K-ras allele.

Animals

Intracellular transport of high molecular weight intermediates of acid alpha-glucosidase in human fibroblasts.

Two transient, high molecular weight precursors of human acid alpha-glucosidase were detected by immune precipitation and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The high molecular weight precursors were rapidly converted into lower molecular weight forms corresponding to previously identified intermediates of acid alpha-glucosidase. An accumulation of these precursors was observed in fibroblasts treated with monensin and nigericin, suggesting that these precursors are intermediates of acid alpha-glucosidase undergoing transport through the Golgi complex.

Animals

Immunologic evaluation in the nutritional assessment of children with cancer.

Eighty-one newly diagnosed untreated pediatric cancer patients (48 hematopoeitic malignancies, 17 solid tumors, 16 benign diseases) were evaluated with immunologic and nutritional parameters. The mean absolute lymphocyte count was adequate in the three groups. Reduced T-lymphocytes were seen in the solid tumors. Mitogenic response of hematopoietic and solid tumor patients' lymphocytes was low. Correlation of immunologic, dietary, and nutritional factors showed that for patients with solid tumors there was a positive significant correlation between weight/height percent and lymphocyte reactivity to phytohemagglutinin, concanavalin A, and pokeweed mitogen (p less than .05). Iron intake showed a significant positive correlation with in vitro mitogen reactivity for the solid tumor group (p less than .05) and benign diseases (p less than 0.01). Immune derangements found among patients with hematopoietic malignancies can be due to replacement of normal bone marrow with malignant cells. In solid tumor patients mitogen reactivity appears to be a reflection of nutritional state, and dietary iron is a possible factor.

Adolescent

Hodgkin's disease complicated by nephrotic syndrome. New clinical observations on the response of both diseases to radiotherapy to the neck.

The clinical course of a 14-year-old boy who developed biopsy-proven minimal change nephrotic syndrome (MCNS) prior to institution of therapy for Hodgkin's disease (HD), mixed cellularity histologic subtype, is presented. In the first week of radiotherapy to the major site of disease in the neck, BUN and creatinine levels rose to 98 mg% and 8.4 mg%, respectively. During the second week of treatment, levels gradually decreased becoming normal in the third week. Body weight gradually decreased in the second week of radiotherapy, falling rapidly in the third and fourth week when diuresis was greatest. Although urine protein concentration fell initially, the concentration remained 1 + or more for 10 weeks following radiotherapy. Following radiotherapy to the neck, staging laparotomy demonstrated a single focus of Hodgkin's disease in the spleen. Radiotherapy was given to the splenic pedicle: six courses of multiagent chemotherapy (MOPP) followed. The boy remains free of any evidence of either HD or MCNS 33 + months from the time of the diagnosis. Circulating lymphocytes showed normal responses to stimulation by phytohemaglutinin, Concanavalin A, and pokeweed mitogens. The patient's monocyte-macrophage-mediated antibody-dependent cellular cytotoxicity (ADCC) was low both prior to and following radiotherapy. Lymphocyte-mediated ADCC was normal at both of these times.

Adolescent

Effect of ascorbic acid in vitro on lymphocyte reactivity to mitogens.

The direct effects of ascorbic acid and dehydroascorbic acid in vitro on human lymphocyte proliferation to phytohemagglutinin (PHA) and concanavalin A (Con A) stimulation were determined. Cells exposed to physiologic and high concentrations of ascorbic acid and dehydroascorbic acid showed poorer tritiated thymidine ([3H]TdR) incorporation than controls without the vitamin. The inhibitory effect was dose-dependent, with the greatest inhibition occurring as the concentration of ascorbic acid and dehydroascorbic acid was increased. At supraoptimal concentrations of PHA and Con A, there was no recovery of the mitogen response, indicating that ascorbic acid did not inhibit the response by competition. Viability studies of cells in culture showed that concentrations of ascorbic acid and dehydroascorbic acid, which consistently inhibited mitogenic stimulation of lymphocytes, were noncytotoxic throughout the culture period. Timed addition of ascorbic acid to PHA-stimulated lymphocytes in culture demonstrated inhibition of [3H]TdR incorporation when ascorbic acid was added as late as 96 hours after initiation of culture. However, the greatest inhibitory effect was observed when ascorbic acid was added at initiation or early in culture. Inhibition was also evident when RNA and protein synthesis were determined. The results suggest that physiologic and high concentrations of ascorbic and dehydroascorbic acid affect early metabolic events in the process of mitogen-stimulated lymphocyte activation.

Ascorbic Acid

A longitudinal study of T and B lymphocytes from a three-year-old patient with severe combined immunodeficiency (SCID) in 'gnotobiotic protection'.

Fluctuations in the percentages and absolute numbers of T and B lymphocytes were observed in the peripheral blood of a patient with severe combined immunodeficiency maintained in a gnotobiotic environment. Up to 24 months of age, 72-86% of the lymphocytes had surface membrane immunoglobulin (SMIg), 37-47% bore a receptor for C3(EAC-RFC), and 3-12.5% formed spontaneous rosettes with sheep erythrocytes (E-RFC). These values persisted until 30 months, after which shifts in the percentages and absolute numbers of T and B cells were observed. A significant decrease in the proportion of SMIg-bearing cells to 20-40% (169-405 mm3), and EAC-RFC to 10.5-39% (114-259 mm3), was accompanied by a general increase in the proportion of T cells to 19-60% (141-1026 mm3), representing a lymphoid subpopulation approach to normal levels.

B-Lymphocytes

Peripheral blood T and B cell characteristics in a patient with severe combined immune deficiency (SCID) maintained in a gnotobiotic environment.

Peripheral blood lymphocytes obtained at 24-30 months after birth from a male with X-linked severe combined immune deficiency maintained in a gnotobiotic environment were characterized by T and B cell surface markers. A high proportion (55-80 percent) of circulating lymphocytes bore surface IgM as detected by direct immunofluorescence. A receptor for the activated C3 complement component was detected on 27-47 percent of his lymphocytes. Only 4-12 percent of the peripheral blood lymphocytes formed spontaneous rosettes with sheep erythrocytes (E-R). In general, no blastogenesis was detected in lymphocyte cultures stimulated with pokeweed mitogen or phytohemagglutinin although transient slightly positive responses to both mitogens were occasionally observed. Incubation of lymphocytes with bovine thymosin Fraction V did not increase the percentage of E-R nor induce lymphocyte blastogenesis in the presence of phytohemagglutinin.

B-Lymphocytes