THE ROLE OF PASSENGER LEUKOCYTES IN THE ANOMALOUS SURVIVAL OF NEONATAL SKIN GRAFTS IN MICE

The anomalous survival of neonatal C3H skin grafts on CBA mice is correlated with the emigration of passenger leukocytes from the graft vasculature. Thus, newborn homografts whose leukocyte populations are eliminated by X-irradiation or by transient sojourn on an intermediate adult C3H host, do not display prolonged survival. Moreover, the continued presence of the newborn grafts is not requisite to the maintenance of the unresponsive state, an observation consonant with the demonstration that CBA mice bearing long-term neonatal C3H skin grafts are leukocyte chimeras. In contrast, neonatal male C57 skin grafts may persist on C57 females after heavy irradiation of the donor, or after passage on an intermediate adult male host. In addition, tolerance is broken by removal of long-persistant newborn grafts from hitherto unresponsive females, and chimerism is not detectable in female C57 mice tolerant of infant male isografts. Finally, leukocytes of neonatal C3H origin, inoculated subcutaneously into CBA males, may occasionally render these animals unresponsive to subsequent adult C3H skin homografts, whereas those taken from infant C57 males usually sensitize their adult female hosts. Thus, passenger leukocytes are implicated in the extended survival of C3H neonatal homografts on CBA recipients, but not in the persistence of H-Y-incompatible neonatal skin isografts on C57 females

SKIN HOMOGRAFTS: TOLEROGENIC VERSUS IMMUNOGENIC INFLUENCES IN MICE

In strain combinations involving multiple non-H-2 disparities, neonatal skin grafts may survive significantly longer than adult grafts of similar genotype on normal adult hosts, and repeatedly outlive grafts of adult origin on immunosuppressed recipients. Moreover, newborn grafts of long-standing may render their hosts unresponsive to adult skin grafts from the same donor strain. With some H-2-compatible strain combinations in which homozygous neonatal grafts are rejected, F1 hybrid (heterozygous) grafts of similar age not only may survive indefinitely, but also may induce tolerance of subsequent adult parental strain homografts. These tolerogenic and gene dosage effects, although much weaker, can likewise be revealed with H-2-incompatible neonatal skin grafts

Ganoderma lucidum (‘Lingzhi’), a Chinese medicinal mushroom : biomarker responses in a controlled human supplementation study

Ageing & Health Group, School of Nursing2003-2004 > Academic research: refereed > Publication in refereed journalVersion of RecordPublishe

Οutcomes for patients who are diagnosed with breast and endometrial cancer

The present study sought to determine the survival outcomes for women diagnosed with breast and endometrial cancer. Using SEER data, a population-based cohort study of women diagnosed with breast and endometrial cancer was conducted. Kaplan-Meier survival curves were created for disease-specific survival rates. A total of 2,027 women diagnosed with breast and endometrial cancer were identified. Of these, 1,296 (63.9%) developed breast cancer first and 731 (36.1%) developed endometrial cancer first. Regional lymph node involvement was significantly more common with a breast cancer diagnosis [522 (25.8%) women] compared with an endometrial cancer diagnosis [87 (4.3%) women] (P<0.05). Factors associated with decreased survival included a high tumor grade in endometrial cancer, nodal positivity and estrogen receptor-negative breast cancer (P<0.05 for each). There were 83 (4.1%) mortalities due to breast cancer, 63 (3.1%) mortalities due to endometrial cancer and 178 (8.8%) mortalities due to other causes (P<0.05). In conclusion, for women diagnosed with breast and endometrial cancer, the cumulative risk of mortality at five years following the second cancer diagnosis is nearly four times more likely to be due to breast cancer than endometrial cancer

Hormone replacement therapy, likely neither angel nor demon

A decline in breast cancer incidence has been attributed to the reduction in hormone replacement therapy (HRT) prescriptions since the publication of the landmark WHIT paper in 2003. Concurrently, a relationship between HRT and cerebrovascular disease incidence has also been suggested. No generalized analysis of HRT prescription rates and breast cancer incidence rates that included more than seven years of data. We hypothesized that detailed analysis of SEER data would clarify the relationship between HRT use and breast cancer incidence. Given the large decline in HRT prescription rates uncovered, analyses of potential complications were also conducted, with the understanding that a small effect or one limited to a subpopulation, such as a single race, might not be detected.Incidence rates (per 100,000 women) and standard errors for ductal and lobular breast carcinomas, and endometrioid /endometrial carcinomas in women over 50 years were obtained from the Surveillance, Epidemiology, and End Results (SEER) database 1992-2012. From the Medical Expenditure Panel Survey 1996-2012 weighted counts and standard errors of hormone replacement therapy (HRT) prescriptions for women over 50 years were obtained. Using the National Hospital Discharge Survey (NHDS), 1996-2010 weighted counts and standard errors of femoral neck fractures, total hip replacements, acute myocardial infarctions, and cerebral infarctions were obtained for 50+ year men and women. Weighted counts and standard errors were divided by US census figures and multiplied by 100,000. Joinpoint regression was used to analyze rates.Beginning 2001, HRT prescription rates dropped dramatically, 2001-2012 AAPC -14.9 (95% CI -17.4, -12.4). Breast cancer rates, which began to decline in 1999, increased after 2003; 2012 rates were similar to those seen in 2001 for both ductal, AAPC 0.1 (-0.4, 0.6) and lobular, AAPC 0.5 (-0.4, 1.5), carcinoma. Endometrial carcinoma rates increased, 2001-2012 AAPC 3.5 (3.1, 3.8), arguing against a negative effect of HRT discontinuation of endometrial carcinoma. Tests for parallelism failed to detect APC differences among genders for femoral neck fractures (P = 0.24), for total hip replacements (P = 0.11), for myocardial infarctions (P = 0.10), or for cerebral infarctions (P = 0.19), precluding any assignment of general effect on these disorders by HRT.Using SEER data, we demonstrated that changes in breast cancer rates cannot be explained by HRT prescription rate changes

Derivation and validation of murine histologic alterations resembling asthma, with two proposed histologic grade parameters

<p>Abstract</p> <p>Background</p> <p>The objective was to define murine histologic alterations resembling asthma in a BALB/c OVA model and to suggest grading criteria. Identified were six salient histologic findings in lungs with putative allergic inflammation: 1) bronchoarterial space inflammation; 2) peri-venular inflammation; 3) inflammation about amuscular blood vessels; 4) inter-alveolar space inflammation, not about capillaries; 5) pleural inflammation; and 6) eosinophils within the inflammatory aggregates. An initial study comprised six groups of twelve mice each: 1) stressed, control; 2) stressed, sensitized; 3) stressed, challenged; 4) not physically stressed, control; 5) not physically stressed, sensitized; 6) not physically stressed, challenged. A second study comprised four experimental groups of twenty mice each: 1) stressed, control; 2) stressed, challenged; 3) not physically stressed, control; 4) not physically stressed, challenged. A third study evaluated two grading criteria, 1) the proportion of non-tracheal respiratory passages with inflammatory aggregates and 2) mitoses in the largest two non-tracheal respiratory passages, in five groups of five mice each, evaluated at different times after the last exposure.</p> <p>Results</p> <p>The first study suggested the six histological findings might reliably indicate the presence of alterations resembling asthma: whereas 82.4% of mice with a complete response had detectable interleukin (IL)-5, only 3.8% of mice without one did; whereas 77.8% of mice with a complete response were challenged mice, only 6.7% of mice without complete responses were. The second study revealed that the six histological findings provided a definition that was 97.4% sensitive and 100% specific. The third study found that the odds of a bronchial passage's having inflammation declined 1) when mitoses were present (OR = 0.73, 0.60 - 0.90), and 2) with one day increased time (OR = 0.75, 0.65 - 0.86).</p> <p>Conclusion</p> <p>A definition of murine histologic alterations resembling asthma in the BALB/c OVA mouse was developed and validated. The definition will be of use in experiments involving this model to ensure that all mice said to have undergone an asthmatic attack did indeed reveal allergic pulmonary inflammation. Proposed grading criteria should be further evaluated with additional studies using physiologic measures of attack severity and increased airway resistance.</p