Browsing by Subject "immunity"
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Item Open Access Diabetic bladder dysfunction is associated with bladder inflammation triggered through hyperglycemia, not polyuria(Research and Reports in Urology, 2018-11-16) Inouye, BM; Hughes, FM Jr; Jin, H; Lütolf, R; Potnis, KC; Routh, JC; Rouse, dc; Foo, WC; Purves, JTPurpose
Diabetes is a grave and progressive condition characterized by debilitating complications. Diabetic bladder dysfunction (DBD) is a very common complication with no specific treatments currently available. Unlike other tissues affected by this disease, the bladder is subjected to two independent insults; 1) polyuria, created by the osmotic effects of glucose in the urine, and 2) hyperglycemia itself. Based on our understanding of inflammation as a major contributor to the underlying organ damage in several other diabetic complications, its presence in the bladder during DBD and the contribution of polyuria and hyperglycemia to its development were assessed.Methods
Awake, restrained cystometry was performed on wild type C57BL/6 mice and diabetic (Akita) mice on a C57BL/6 background at 15 weeks of age. A subgroup of the Akita mice were treated with phlorizin, an inhibitor of sodium-glucose linked transporter types 1 and 2 that prevents glucose reabsorption in the kidney. All groups were assessed for serum glucose, 4-hour voiding totals, and inflammation in the bladder (Evans blue assay).Results
Akita mice develop cystometrically-defined DBD by 15 weeks of age, as evidenced by an increase in urinary frequency, a decrease in voiding volume, and an increase in post-voiding residual volume. Phlorizin effectively normalized serum glucose in these animals while increasing the urine output. Inflammation in the bladder was present in the diabetic animals at this time point, but not detectable in animals receiving phlorizin.Conclusion
Inflammation in the bladder of diabetic mice correlates with the development of DBD and is triggered by hyperglycemia, not polyuria.Item Open Access Novel genetic variants of PIP5K1C and MVB12B of the endosome-related pathway predict cutaneous melanoma-specific survival.(American journal of cancer research, 2020-01) Lu, Guiqing; Zhou, Bingrong; He, Yuanmin; Liu, Hongliang; Luo, Sheng; Amos, Christopher I; Lee, Jeffrey E; Yang, Keming; Qureshi, Abrar; Han, Jiali; Wei, QingyiEndosomes regulate cell polarity, adhesion, signaling, immunity, and tumor progression, which may influence cancer outcomes. Here we evaluated associations between 36,068 genetic variants of 228 endosome-related pathway genes and cutaneous melanoma disease-specific survival (CMSS) using genotyping data from two previously published genome-wide association studies. The discovery dataset included 858 CM patients with 95 deaths from The University of Texas MD Anderson Cancer Center, and the replication dataset included 409 CM patients with 48 deaths from the Nurses' Health Study (NHS) and the Health Professionals Follow-up Study (HPFS). In multivariate Cox proportional hazards regression analysis, we found that two novel SNPs (PIP5K1C rs11666894 A>C and MVB12B rs12376285 C>T) predicted CMSS, with adjusted hazards ratios of 1.47 (95% confidence interval = 1.15-1.89 and P = 0.002) and 1.73 (1.30-2.31 and 0.0002), respectively. Combined analysis of risk genotypes of these two SNPs revealed a dose-dependent decrease in CMSS associated with an increased number of risk genotypes (P trend = 0.0002). Subsequent expression quantitative trait loci (eQTL) analysis revealed that PIP5K1C rs11666894 was associated with mRNA expression levels in lymphoblastoid cell lines from 373 European descendants (P<0.0001) and that MVB12B rs12376285 was associated with mRNA expression levels in cultured fibroblasts from 605 European-Americans (P<0.0001). Our findings suggest that novel genetic variants of PIP5K1C and MVB12B in the endosome-related pathway genes may be promising prognostic biomarkers for CMSS, but these results need to be validated in future larger studies.Item Open Access SARS-CoV-2 reinfection across a spectrum of immunological states.(Health science reports, 2022-07-22) McKittrick, Justine M; Burke, Thomas W; Petzold, Elizabeth; Sempowski, Gregory D; Denny, Thomas N; Polage, Christopher R; Tsalik, Ephraim L; McClain, Micah TPurpose
Several cases of symptomatic reinfection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) after full recovery from a prior episode have been reported. As reinfection has become an increasingly common phenomenon, an improved understanding of the risk factors for reinfection and the character and duration of the serological responses to infection and vaccination is critical for managing the coronavirus disease 2019 (COVID-19) pandemic.Methods
We described four cases of SARS-CoV-2 reinfection in individuals representing a spectrum of healthy and immunocompromised states, including (1) a healthy 41-year-old pediatrician, (2) an immunocompromised 31-year-old with granulomatosis with polyangiitis, (3) a healthy 26-year-old pregnant woman, and (4) a 50-year-old with hypertension and hyperlipidemia. We performed confirmatory quantitative reverse transcription-polymerase chain reaction and qualitative immunoglobulin M and quantitative IgG testing on all available patient samples to confirm the presence of infection and serological response to infection.Results
Our analysis showed that patients 1 and 2, a healthy and an immunocompromised patient, both failed to mount a robust serologic response to the initial infection. In contrast, patients 3 and 4, with minimal comorbid disease, both mounted a strong serological response to their initial infection, but were still susceptible to reinfection.Conclusion
Repeat episodes of COVID-19 are capable of occurring in patients regardless of the presence of known risk factors for infection or level of serological response to infection, although this did not trigger critical illness in any instance.