An essential E box in the promoter of the gene encoding the mRNA cap-binding protein (eukaryotic initiation factor 4E) is a target for activation by c-myc.

The mRNA cap-binding protein (eukaryotic initiation factor 4E [eIF4E]) binds the m7 GpppN cap on mRNA, thereby initiating translation. eIF4E is essential and rate limiting for protein synthesis. Overexpression of eIF4E transforms cells, and mutations in eIF4E arrest cells in G, in cdc33 mutants. In this work, we identified the promoter region of the gene encoding eIF4E, because we previously identified eIF4E as a potential myc-regulated gene. In support of our previous data, a minimal, functional, 403-nucleotide promoter region of eIF4E was found to contain CACGTG E box repeats, and this core eIF4E promoter was myc responsive in cotransfections with c-myc. A direct role for myc in activating the eIF4E promoter was demonstrated by cotransfections with two dominant negative mutants of c-myc (MycdeltaTAD and MycdeltaBR) which equally suppressed promoter function. Furthermore, electrophoretic mobility shift assays demonstrated quantitative binding to the E box motifs that correlated with myc levels in the electrophoretic mobility shift assay extracts; supershift assays demonstrated max and USF binding to the same motif. cis mutations in the core or flank of the eIF4E E box simultaneously altered myc-max and USF binding and inactivated the promoter. Indeed, mutations of this E box inactivated the promoter in all cells tested, suggesting it is essential for expression of eIF4E. Furthermore, the GGCCACGTG(A/T)C(C/G) sequence is shared with other in vivo targets for c-myc, but unlike other targets, it is located in the immediate promoter region. Its critical function in the eIF4E promoter coupled with the known functional significance of eIF4E in growth regulation makes it a particularly interesting target for c-myc regulation.

Characterization of neutron reference fields at US Department of Energy calibration fields.

The Health Physics Measurements Group at the Los Alamos National Laboratory (LANL) has initiated a study of neutron reference fields at selected US Department of Energy (DOE) calibration facilities. To date, field characterisation has been completed at five facilities. These fields are traceable to the National Institute for Standards and Technology (NIST) through either a primary calibration of the source emission rate or through the use of a secondary standard. However, neutron spectral variation is caused by factors such as room return, scatter from positioning tables and fixtures, source anisotropy and spectral degradation due to source rabbits and guide tubes. Perturbations from the ideal isotropic point source field may impact the accuracy of instrument calibrations. In particular, the thermal neutron component of the spectrum, while contributing only a small fraction of the conventionally true dose, can contribute a significant fraction of a dosemeter's response with the result that the calibration becomes facility-specific. A protocol has been developed to characterise neutron fields that relies primarily on spectral measurements with the Bubble Technology Industries (BTI) rotating neutron spectrometer (ROSPEC) and the LANL Bonner sphere spectrometer. The ROSPEC measurements were supplemented at several sites by the BTI Simple Scintillation Spectrometer probe, which is designed to extend the ROSPEC upper energy range from 5 to 15 MeV. In addition, measurements were performed with several rem meters and neutron dosemeters. Detailed simulations were performed using the LANL MCNPX Monte Carlo code to calculate the magnitude of source anisotropy and scatter factors.

Regulation of cyclin D1 and p16(INK4A) is critical for growth arrest during mammary involution.

A coordinated growth arrest during mammary involution completes the dramatic changes in mammary cell proliferation seen during pregnancy and lactation. Signals regulating this arrest are poorly understood, despite their potential relevance to oncogenesis. Here we report that the arrest involves a unique pulse of p16(INK4A) expression in vivo, which accompanies decreased cyclin D1 expression and a shift to an active repressor E2F4 complex. We used INK4A/ARF-/- mice as well as cyclin D1 and p16(INK4A) transgenic strains to examine the physiological significance of these patterns. p16(INK4A) directly regulated the in vivo transition from E2F3 to E2F4 as the major E2F DNA binding activity, and its contribution to growth arrest was independent of cyclin D1. Transgenic cyclin D1 expression prevented normal terminal differentiation by ablating the p16(INK4A) pulse, abolishing the shift from E2F3 to E2F4, derepressing E2F target genes, and expanding a stem cell population. The effects of cyclin D1 were reversed by restoring p16(INK4A) but were not seen in INK4A/ARF-/- mice. Our results indicate that cyclin D1 may contribute to tumorigenesis by altering cell differentiation and demonstrate a significant function for p16(INK4A) in development in vivo. These regulatory mechanisms used during mammary involution offer a potential explanation for the protective effect of pregnancy against breast cancer.

Cyclin D1 (PRAD1) alternative transcript b: full-length cDNA cloning and expression in breast cancers.

The cyclin D1/PRAD1 protooncogene is a key regulator of the G1 phase of the cell cycle and has been incriminated in the pathogenesis of a variety of primary human tumors. Recently, part of a novel alternatively spliced cyclin D1 transcript, called transcript b, has been identified. This variant transcript showed a failure of splicing at the 3' end of exon 4 and as a result, the expected protein product is altered at its C-terminus. Because of similar transcript sizes, previous Northern analyses would not have been expected to distinguish the two variants, and the relative levels of the two cyclin D1 transcripts in human tumors is unknown. To elucidate the role of cyclin D1 transcript b, we have isolated cDNA clones of this variant transcript from human breast cancer cell lines and report the sequence of the entire coding region of the cDNA. The protein predicted from the cDNA sequence consists of 274 amino acid residues and lacks a PEST sequence in its C-terminus. Examination of the levels of the two alternative cyclin D1 transcripts in primary breast cancers and breast cancer cell lines by Northern blot analysis and reverse transcription-polymerase chain reaction (RT-PCR) assays showed that the variant transcript b is indeed expressed in primary breast cancers and breast cancer cell lines, but the level of transcript b is dramatically lower than that of the originally reported transcript a of the cyclin D1 gene. In breast cancers, oncogenic overexpression of cyclin D1 mRNA appears to consist overwhelmingly of transcript a, and the role of transcript b, if any, in oncogenesis remains to be established. Science Ireland Ltd.

High dose intravenous immunoglobulin therapy in burn patients: pharmacokinetics and effects on microbial opsonization and phagocytosis.

Depressed serum immunoglobulin levels following severe burns may lead to subsequent infectious complications following such injuries. In a randomized study we administered multiple doses of Sandoglobulin (500 mg/kg) or albumin intravenously to patients with severe burn injuries and closely monitored serum IgG levels. Patients who received IgG therapy had earlier return of normal serum IgG levels compared to control patients; however, control patients attained normal IgG levels during the second postburn week. Serum half-lives of IgG following infusions were remarkably short (means, 47 hours for infusions within 3 days of injury and 154 hours for infusions in the third postburn week); Sandoglobulin has been reported to have approximately a 21-day half-life in normal individuals. We also measured the opsonic capacity of postburn serum, using fluorescein-labeled microbes and flow cytometry; we identified postburn opsonic defects with certain of the organisms as late as 15 days postinjury, even though serum IgG levels had normalized. These defects were corrected by the in vitro addition of Sandoglobulin to the incubation mixture.

Temporal analysis of murine lymphocyte subpopulations by monoclonal antibodies and dual-color flow cytometry after burn and nonburn injury.

The immune suppression that frequently accompanies severe injury undoubtedly contributes to subsequent infectious complications. Various lymphocyte subpopulations may be identified by surface antigen expression, and alterations in antigen expression by lymphocytes may reflect host immune competence. Using monoclonal antibodies (Moabs) and dual-color flow cytometry, we studied lymphocyte phenotypic expression in mice after either controlled burn injury or hind-limb amputation, with use of peripheral blood, lymph node, and spleen for cell preparation. Moabs were utilized specific for T cells (Lyt-1), helper/inducer cells (L3T4), suppressor/cytotoxic cells (Lyt-2), B cells (IgG), and activated T cells (Ia or IL-2 receptor). The assay techniques called for small amounts of tissue and avoided gradient procedures that might result in selective loss of some lymphocyte populations. The most consistent changes observed were depressions in percentages of L3T4+ and Lyt-2+ cells in spleens of burned mice, accompanied by depression in Ia+ (possibly activated or proliferating) subsets of L3T4+ and Lyt-2+ cells, and the appearance of increased percentages of non-B, non-T lymphocytes. Changes in lymph node cells were minimal. The major alteration seen in peripheral blood was substantial depression of Ia+ subsets, although burned mice had increased circulating Lyt-2+ cells on several late postburn days. Burned mice, unlike limb-trauma mice, had marked splenic hypertrophy with more than a 300% increase in spleen weight after the 30-day postburn period. Eschar excision/implantation experiments indicated that splenic hypertrophy and splenocyte phenotypic changes are related to the presence of burned tissue, which suggests that burned tissue may partially mediate immune changes that accompany severe burn injury.

Perception of breast cancer risk among women in breast center and primary care settings: correlation with age and family history of breast cancer.

BACKGROUND: A great deal of information about breast cancer risk is available to the public. The accuracy of impressions formed from this information is unknown. METHODS: A total of 750 women attending a breast center and 112 women attending a primary care office completed written surveys of their perceptions of average population risk, personal lifetime risk, and personal 10-year risk of getting breast cancer. Data sufficient to apply the Gail model were obtained, and a calculated estimate of risk was generated. Ratios of perceived to calculated risk were correlated with the respondent's age, family history of breast cancer, and location in a breast center or primary care office. RESULTS: Women in both practice settings overestimated population risk by more than twofold. Eighty percent overestimated personal lifetime risk by more than 50% and 35% by more than fivefold. Only 7% significantly underestimated risk. Ten-year risk estimates were even more inaccurate, with 69% overestimating risk by more than fivefold, 46% by more than 10-fold, and 17% by more than 20-fold. Results from a primary care population were nearly identical. Women at the extremes of age were most inaccurate in estimating risk. It was surprising that family history had little impact on perception of personal risk. CONCLUSIONS: Women in both breast center and primary care settings have a fals:ly high perception of both short-term and long-term breast cancer risk. Health care providers should recognize these misconceptions and be aware that many women may benefit from risk counseling.

Improving residents' clinical skills with the structured clinical instruction module for breast cancer: results of a multiinstitutional study. Breast Cancer Education Working Group.

BACKGROUND: The purpose of this study was to determine, in a multiinstitutional setting, the effectiveness of the structured clinical instruction module (SCIM) as an instructional format for surgical residents. METHODS: The breast cancer SCIM is an abbreviated (3-hour) clinical skills course that places residents in realistic clinical settings. The curriculum encompasses all aspects of breast cancer patient assessment. The SCIM was administered to 137 residents at five institutions. Sixty-six faculty members and 52 patients participated. All participants were surveyed with multiitem questionnaires. The residents were also asked to perform a self-assessment of their skills before and after the SCIM. RESULTS: The SCIM was delivered at all institutions without difficulty. All participants rated the SCIM highly (from "above average" to "outstanding"). Mean ratings (on a 5-point scale) for the overall effectiveness of the SCIM as an educational format follow: [table: see text] The pretest mean (on a 5-point scale) on the self-assessment was 2.46 ("less than competent"); the posttest mean was 3.54 ("more than competent") (p < 0.0001). CONCLUSIONS: Residents are acutely aware of their deficiencies in understanding breast cancer. The SCIM is a standardized, reproducible, portable, and effective educational vehicle.

Recurrence patterns and outcome in 1019 patients undergoing axillary or inguinal lymphadenectomy for melanoma.

Patterns of recurrence and outcome were determined in 403 patients with melanoma who underwent an axillary or inguinal lymphadenectomy. Recurrences developed at single sites in 291 (72%) patients, with a median survival of 11 months, and at multiple sites in 112 (28%) patients, with a median survival of 3 months. Among patients with single-site recurrence, those with nonvisceral recurrence (n = 190) had a median survival of 18.5 months compared with 6 months in those with visceral recurrence (n = 101). Recurrences were treated surgically in 240 (60%) patients, with a median survival of 15 months, and nonsurgically in 112 patients, with a median survival of 4 months. Median survival after complete resection of single-site recurrence was 19 months compared with 6 months after incomplete resection. Multivariate analysis revealed that outcome was improved by surgical treatment, single-site and nonvisceral recurrence, and primary site in an extremity. These observations support an approach of selective resection in the treatment of recurrences after lymphadenectomy.

Multimodality management of Merkel cell carcinoma.

HYPOTHESIS: Merkel cell carcinoma is a rare dermal neuroendocrine carcinoma whose optimal treatment and prognostic factors are poorly defined. We hypothesize that high-risk patients with Merkel cell carcinoma are best treated with multimodality therapy. DESIGN: A retrospective review of all patients (N = 33) with Merkel cell carcinoma treated at the Massachusetts General Hospital from January 1, 1980, to August 24,1997. Median follow-up time was 37 months (range, 6-157 months). PATIENTS: Adequate data for evaluation were available for 31 patients. Male to female distribution was 14 men and 17 women, with a median patient age of 68 years. MAIN OUTCOME MEASURE: Stage at presentation; factors associated with recurrence; and the effects of surgery, radiation therapy (XRT), and chemotherapy on recurrence, salvage, and survival rates. RESULTS: There were 12 extremity, 11 head and neck, and 8 truncal tumors. There were 22 isolated primary tumors, 8 with additional clinically positive lymph nodes, and 1 with distant disease. Therapy was local excision with or without XRT in 19 patients, local resection and lymphadenectomy with or without XRT in 8 patients, and XRT alone in 4 patients with head and neck tumors. Fifteen patients developed recurrences (7 local, 8 nodal, and 10 distant). Median time to recurrence was 8 months (range, 3-48 months). There were 7 tumor-related deaths, 6 of which were associated with truncal lesions (P<.001). No locoregional recurrences occurred in patients with margins of resection of 2 cm or greater or adequate XRT. A multivariate analysis selected truncal location (P = .005) and nodal disease (P = .05) as predictors of mortality. Remission was possible in 5 patients with locoregional and 2 patients with distant recurrences. CONCLUSIONS: Merkel cell carcinoma is an aggressive dermal cancer with frequent nodal metastases; truncal tumors have the worst prognosis. Locoregional recurrence correlates with inadequate margins and lack of XRT, but remission is possible with multimodality therapy.

Surgical management of phyllodes tumors.

HYPOTHESIS: Although phyllodes tumors have minimal metastatic potential, we hypothesized that they have a proclivity for local recurrence and should be excised with a wide margin. We reviewed the clinical and radiological appearance of phyllodes tumors and analyzed the role of surgical treatment in their management. DESIGN: Medical records, imaging studies, pathology reports, and interventions were reviewed. SETTING: A large tertiary care teaching hospital. PATIENTS: Between 1980 and 1997, 40 patients with phyllodes tumors were identified through the tumor registry at the Massachusetts General Hospital, Boston. MAIN OUTCOME MEASURES: Surgical resection margins, rates of local recurrence, incidence of distant metastases, and survival. RESULTS: All 40 patients were female, with a mean age of 41 years. Each patient had a palpable mass or a mammographic finding that was indistinguishable from a fibroadenoma on examination. Tumor size ranged from 5 mm to 28 cm. Local recurrence correlated with excision margins (P<.05), but not with tumor grade or size. Local recurrence occurred in 5 patients, each of whom had positive margins or margins less than 1 cm after excision. After reexcision with a 1-cm margin, these individuals remained free of recurrence. One patient developed metastatic disease after total mastectomy and died after chemotherapy. CONCLUSIONS: Phyllodes tumors mimic fibroadenomas and are often excised with close margins. Primary excision or reexcision with a 1-cm margin is recommended. Mastectomy is indicated for patients with large lesions. Lymph node metastases are unusual and occur secondary to necrotic tumor. Chemotherapy is based on guidelines for the treatment of sarcomas, not breast adenocarcinoma.

Outcome of patients with melanoma and histologically negative sentinel lymph nodes.

HYPOTHESIS: Patients with melanoma and histologically negative sentinel lymph nodes identified by lymphatic mapping have a very good prognosis. DESIGN: Cohort study with follow-up information obtained from medical records and telephone interviews. SETTING AND PATIENTS: Of all patients with cutaneous melanoma who underwent intraoperative sentinel lymph node mapping between November 15, 1993, and April 18, 1997, at the Massachusetts General Hospital, Boston, 89 were found to have no evidence of melanoma in their sentinel nodes. Forty-six lesions (51%) were on an extremity and 44 (49%) were of axial location. The median tumor thickness was 1.8 mm (range, 0.36-12.0 mm) and 11 tumors (12%) were ulcerated. INTERVENTIONS: Patients underwent intraoperative sentinel lymph node mapping with lymphazurin and radiolabeled sulfur colloid. Sentinel lymph nodes were analyzed by standard hematoxylin-eosin staining. Only 2 patients received adjuvant therapy following wide excision of the primary lesion. MAIN OUTCOME MEASURES: Site of initial recurrence and time to initial recurrence. RESULTS: The median follow-up for all patients was 23 months (range, 2-54 months). Eleven patients (12%) developed melanoma recurrences, and 78 (88%) patients remain disease free. Regional lymph nodes were the initial site of recurrence in 7 (8%) of 89 patients, and 7 (7%) of 106 mapped basins. Four patients had recurrence without involvement of regional lymph nodes: 2 with distant metastases and 2 with in transit metastases. The median time to recurrence was 12 months (range, 2-35 months). Sentinel lymph nodes were reanalyzed using serial sections and immunoperoxidase stains in 7 patients with recurrence and metastatic melanoma was identified in 3 (43%). CONCLUSIONS: The risk for melanoma recurrence is relatively low in patients with histologically negative sentinel nodes identified by lymphatic mapping. Longer follow-up will improve our understanding of the prognostic value of this procedure.

Lymphedema after sentinel lymph node biopsy for cutaneous melanoma: a report of 5 cases.

BACKGROUND: Sentinel lymph node (SLN) biopsy has rapidly become the procedure of choice for assessing the lymph node status of patients with 1992 American Joint Committee on Cancer stages I and II melanoma. The procedure was designed to be less invasive and, therefore, less likely to cause complications than a complete lymph node dissection. To our knowledge, this is the first report in the literature documenting extremity lymphedema following SLN biopsy. OBSERVATION: We report 5 cases of lymphedema after SLN biopsy in patients being routinely followed up after melanoma surgery at the Massachusetts General Hospital Melanoma Center, Boston. Three cases were mild, and 2 were moderate. Potential contributing causes of lymphedema were present in 4 patients and included the transient formation of hematomas and seromas, obesity, the possibility of occult metastatic melanoma, and the proximal extremity location of the primary melanoma excision. Four of the patients underwent an SLN biopsy at our institution. We used the total number of SLN procedures (N = 235) that we have performed to calculate a 1.7% baseline incidence of lymphedema after SLN biopsy. CONCLUSIONS: Sentinel lymph node biopsy can be complicated by mild and moderate degrees of lymphedema, with an incidence of at least 1.7%. Some patients may have contributing causes for lymphedema other than the SLN biopsy, but many of these causes are difficult to modify or avoid.

Gamma probe guided biopsy of the sentinel node in malignant melanoma: a multicentre study.

Sentinel lymph node biopsy was attempted in 336 patients with clinically node-negative cutaneous melanoma. All patients were injected with technetium-99m labelled radiocolloid, with 108 patients simultaneously receiving vital blue dye for sentinel node identification. Sentinel lymph nodes were identified in 329 patients, giving a technical success rate of 97.9%. Metastatic disease was identified in 39 (11.9%) of the patients in whom sentinel nodes were found. Patients with negative sentinel nodes were observed and patients with positive sentinel nodes underwent comprehensive lymph node dissection. The presence of metastatic disease in the sentinel nodes and primary tumour depth by Breslow or Clark levels were joint predictors of survival based on Cox proportional hazards modelling. Disease recurrences occurred in 26 (8.8%) patients with negative sentinel lymph nodes, with isolated regional recurrences as the first site in 10 (3.4%). No patients with Clark level II primary tumours were found to have positive sentinel nodes or disease recurrences. One patient with a thin (<0.75 mm) Clark level III primary had metastatic disease in a sentinel node. Patients with metastases confined to the sentinel nodes had similar survival rates regardless of the number of nodes involved.

Localization of regional lymph nodes in melanomas of the head and neck.

OBJECTIVES: To study the efficacy of gamma-probe radiolocalization of the first draining (sentinel) lymph node (SLN) in stage N0 melanoma of the head and neck and to evaluate its potential role in the staging and treatment of this disease. DESIGN: Gamma-probe radiolocalization, a new alternative to blue-dye lymphatic mapping, uses a scintillation (gamma) probe to identify radiolabeled SLNs. In a consecutive sample clinical trial, gamma-probe radiolocalization of the SLN is compared with lymphoscintigraphy and blue-dye lymphatic mapping. Follow-ups ranged from 1.7 years to 4 years, with a mean follow-up of 2.5 years. SETTING: Tertiary and private care teaching hospital. PATIENTS: Between June 1993 and November 1995, 23 patients with stage N0 intermediate-thickness melanoma of the head and neck were enrolled in this volunteer sample. INTERVENTIONS: Twenty-four hours prior to surgery, a radioactive tracer was intradermally injected around the circumference of a primary melanoma. Twelve patients also had blue dye injected just prior to surgical resection. Using a handheld gamma probe, radiolabeled lymph nodes were identified and selectively removed with minimal dissection. In patients with nodes with histologic evidence of metastases, a regional lymphadenectomy was performed. MAIN OUTCOME MEASURES: The successful identification of radiolabeled SLNs, the correlation of SLN radiolabeling to lymphoscintigraphy and blue-dye mapping, and the long-term development of regional metastases. RESULTS: Surgeons successfully resected the radiolabeled SLNs in 22 (96%) of 23 patients. The success rate of blue-dye lymphatic mapping was 8 (75%) of 12 patients and lymphoscintigraphy was 20 (91%) of 22 patients. One hundred percent of blue-stained lymph nodes were radiolabeled. The one patient in whom no SLN could be identified developed regional disease at 17 months. CONCLUSIONS: Gamma-probe radiolocalization and resection of the radiolabeled SLN is a simple and reliable method of staging regional lymph nodes and determining the need for elective lymphadenectomy.

Absence of mutagenic effects of continuous and pulsed ultrasound in cultured (AL) human-hamster hybrid cells.

Mutagenic effects of continuous and pulsed ultrasound were looked for using an in vitro assay system, the AL hybrid, that is up to 100 times more sensitive for mutagens such as x-rays and neutrons than the assays used previously to evaluate ultrasound. Cells in suspension in rotated plastic test tubes were insonated with continuous wave ultrasound at 1 MHz, ISPTP = 0.62-40 W/cm2 for 0-40 min. Cells attached in the central region of culture flasks received pulsed exposures at fc = 2.5 MHz, PRF = 1 kHz, 2 and 8 cycles per pulse, with p- = 1.2 MPa (ISPTA = 31-180 mW/cm2) for 0-30 min. Although these exposures were cytotoxic (the plating efficiency was decreased to approximately 65% by the highest doses), induction of mutation, if any occurred, was less than would be expected in this test system from 10-30 cGy of x-ray.

Hirschsprung's disease in a kindred: a possible clue to the genetics of the disease.

A nine generation kindred, the first generation dating back to the early 18th century, existing in the Mennonite population of central Pennsylvania is described in terms of the incidence of documented and presumptive Hirschsprung's disease. This kindred was developed by tracing back family lines, by the use of the "circle letter" and three family history books, and by personal interviews with key family members. In the ninth (current) generation, involving at least 5 families, 8 out of 14 children (57%) have documented evidence of Hirschsprung's disease; 4 out of 14 had congenital deafness (29%); 2 had Waardenburg's syndrome (14%); and 1 had Down's syndrome (7%). Only 1 out of the 14 had total colonic involvement. Investigation of the sixth-ninth (last 4) generations shows 22 out of 100 (22%) to have definite or strongly presumptive evidence of Hirschsprung's disease. The opportunity to study this unique kindred, which can be traced back to a single source, exhibiting a very high incidence of Hirschsprung's disease with an unusually high incidence of associated congenital anomalies and without significant association of total colonic disease has provided us with a better understanding of the genetics underlying this disease.

The effect of thermal injury on murine neutrophil oxidative metabolism.

The ability of polymorphonuclear leukocytes to kill bacteria and yeast is reflected by cellular chemiluminescence or similarly by the production of H2O2 during oxidative metabolism. With the use of flow cytometry and 2'7' dichlorodihydrofluorescein-diacetate, we determined the direct effect of thermal injury and the indirect effect of burn serum on murine polymorphonuclear leukocyte oxidative metabolism after stimulation on days 1, 5, and 10 after 25% total body surface area burn. Control or burn peritoneal leukocytes and 10% control or burn serum were incubated in vitro with 2'7' dichlorodihydrofluorescein-diacetate for 15 minutes, then stimulated with phorbol 12-myristate 13-acetate. The change in polymorphonuclear leukocyte fluorescence was calculated from fluorescence histograms before and after stimulation. The oxidative metabolism of burn polymorphonuclear leukocytes was clearly depressed on days 5 and 10 after burn injury. Control polymorphonuclear leukocytes in the presence of day 5 burn serum produced decreased levels of H2O2, returning to normal by day 10. In general, bactericidal activity is markedly depressed on days 5 and 10 after thermal injury and may be associated with increased risk of sepsis.

Immune response modulation after burn injury: T cells and antibodies.

Studies have been conducted to characterize phenotypic and functional characteristics of murine and human cells after burn injury. The detailed analysis of T-cell distribution in the burned mouse, and the analysis of activation markers L3T4/Lyt-2 and Ia, reveals characteristic changes including the presence of "activated" suppressor cells during post-injury suppression. Studies of humoral markers suggest an increased production of IgG in burned animals upon sheep red blood cells (SRBC) challenge, accompanied by increased clearance or catabolism of serum antibody, which results in depressed serum levels. Finally, in vitro phagocytosis studies using fluorescein isothiocyanate (FITC)-labeled killed bacteria reveal that burn patient sera are clearly defective in their ability to promote opsonization of one or more specific organisms by neutrophils. The addition of exogenous IgG to the incubation medium improves this response, suggesting that postburn phagocytic depression is an opsonic defect, rather than an inhibitory effect of burn serum on neutrophils.

Partitioning of 222Rn entry into a structure surrounded by soil.

This paper describes the entry rate of 222Rn into a basement structure surrounded by a sandy clay loam soil. The highest indoor radon concentrations occurred when the rate of entry was lowest. Data from in-situ measurements were used to identify the entry pathways and also the origins of the radon during periods when the entry rate was low. Results indicated that 25% of the radon entered through the floor-wall joint and 75% through the floor and walls. About 30% of the radon originated in the concrete. Diffusion was the primary transport mechanism. However, radon entry through the floor-wall joint was a combination of diffusion and a convective flow between the subslab region and the interior of the structure.