The potential clinical utility of serum α-protryptase levels

Background: Because biopsy criteria for diagnosing systemic mastocytosis are not precise, the value of serum α-protryptase levels in the work-up of suspected systemic mastocytosis should be considered. Objective: A retrospective analysis was performed on subjects with total tryptase serum levels that were high (≥20 ng/mL), while β-tryptase serum levels were normal (<1 ng/mL) or modestly elevated (1 to 5 ng/mL). Methods: Over a 3.5-year period, 52 qualifying specimens were identified from 1369 consecutive samples. The corresponding subjects were divided into those with suspected mastocytosis and those with suspected anaphylaxis. Subjects with suspected mastocytosis were subdivided into 3 subgroups on the basis of biopsy results (positive, negative, or not available). Subjects with suspected anaphylaxis were subdivided into living and deceased subgroups. Results: Among the 15 subjects who underwent biopsy, α-protryptase serum levels (the difference between directly-measured levels of serum total tryptase and β-tryptase), when greater than 75 ng/mL (n = 9), were always associated with a positive biopsy result for systemic mastocytosis; levels from 20 to 75 ng/mL (n = 6) were associated with a positive biopsy result in 50% of subjects. α-Protryptase serum levels may be a more sensitive screening test than a bone marrow biopsy for this disorder. Also, elevated α-protryptase serum levels in some adult patients return to normal over time, suggesting that mast cell hyperplasia resolved in these patients. Finally, a high α-protryptase level may reveal anaphylaxis to be a presenting manifestation of systemic mastocytosis or mast cell hyperplasia. Conclusion: Levels of serum α-protryptase, relative to those of β-tryptase, appear to be useful in the diagnostic work-up and follow-up of subjects with suspected systemic mastocytosis. (J Allergy Clin Immunol 1999;103:1092-9.)     

性腺轴激素分泌的节律性变化及临床意义

目的探讨性腺轴激素的节律性变化规律及其对临床诊断治疗的指导意义.方法采用Beckman-Coulter ACCESS全自动微粒子化学发光免疫分析系统,分别测定了30例健康成年男性上午8点和下午4点的血清催乳素(PRL)、黄体生成素(LH)、卵泡刺激素(FSH)、雌二醇(E2)和睾酮(T)的水平,并将不同时间段的结果分别进行配对t检验分析.结果 PRL 和T的血清水平上午8点均显著高于下午4点(P＜0.01),而E2、LH和FSH血清水平在这两个时间段没有显著性差异(P＞0.05).结论部分性腺轴激素在1天的不同时间段有波动,尤其是PRL和T,建议临床上对性腺轴激素的监测应采集同一时间段的标本进行分析.     

The potential clinical utility of measuring severe acute respiratory syndrome coronavirus 2-specific T-cell responses

BackgroundBoth humoral and cell-mediated responses are associated with immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although our understanding of the potential role of T-cell responses in the context of coronavirus disease 2019 (COVID-19) is rapidly increasing, more information is still needed.ObjectivesTo provide an overview of the role of T-cell immunity in COVID-19, in the context of natural infection and post-vaccination, and discuss the potential utility of measuring SARS-CoV-2-specific T-cell responses, drawing on experience of the use of interferon-γ release assays (IGRAs) in tuberculosis (TB).SourcesPubMed articles up to 16 April 2021.ContentT-cell responses can be detected very early in the course of COVID-19, earlier than the detection of antibody responses, and are correlated with COVID-19 outcome. Lower CD4⁺ and CD8⁺ T-cell counts are markers of more severe disease, longer duration of viral RNA positivity and increased mortality. In line with natural infection, SARS-CoV-2 vaccination stimulates robust T-cell responses, which probably play an important role in protection; data on long-term T-cell responses are currently limited. The utility of measuring T-cell responses is already well established in both aiding the diagnosis of TB infection using IGRAs, and evaluation of T-cell responses to TB vaccine candidates. A variety of assays have already been developed to measure SARS-CoV-2-specific T-cell responses, including IGRAs, intracellular cytokine staining and activation-induced markers. IGRAs based on SARS-CoV-2 antigens can distinguish between convalescent and uninfected healthy blood donors.ImplicationsSimple assays for measuring the quantity and function of T-cell responses may have utility in the prognostication of COVID-19, and for monitoring immune responses to SARS-CoV-2 vaccination and population-based immunity to SARS-CoV-2 variants of interest.     

Catalytic antibodies to HIV: physiological role and potential clinical utility

Immunoglobulins (Igs) in uninfected humans recognize residues 421-433 located in the B cell superantigenic site (SAg) of the HIV envelope protein gp120 and catalyze its hydrolysis by a serine protease-like mechanism. The catalytic activity is encoded by germline Ig variable (V) region genes, and is expressed at robust levels by IgMs and IgAs but poorly by IgGs. Mucosal IgAs are highly catalytic and neutralize HIV, suggesting that they constitute a first line of defense against HIV. Lupus patients produce the Igs at enhanced levels. Homology of the 421-433 region with an endogenous retroviral sequence and a bacterial protein may provide clues about the antigen driving anti-SAg synthesis in lupus patients and uninfected subjects. The potency and breadth of HIV neutralization revives hopes of clinical application of catalytic anti-421-433 Igs as immunotherapeutic and topical microbicide reagents. Adaptive improvement of anti-SAg catalytic Igs in HIV infected subjects is not customary. Further study of the properties of the naturally occurring anti-SAg catalytic Igs should provide valuable guidance in designing a prophylactic vaccine that amplifies protective catalytic immunity to HIV.     

Heparin-induced increase in serum levels of aminotranferases. A controlled clinical trial

Sixty-four patients over the age of 40 years, undergoing elective surgery of at least one hour's duration, were randomized to treatment with either a thromboembolic deterrent ( TED ) stocking (Kendall Co.) or subcutaneous low-dose heparin 5 000 IU every 12 hours. Serum levels of alanine aminotransferase (S-ALAT), aspartate aminotransferase (S-ASAT), gamma-glutamyl transpeptidase (S-gamma-GT) and alkaline phosphatase (S-ALP) were measured. S-ALAT increased significantly on the 5th and 10th postoperative day, from 27 +/- 2 (x +/- SE) to 40 +/- 4 (p less than 0.01) and 55 +/- 7 U/l (p less than 0.001), respectively, in the heparin group and was significantly higher in the heparin than in the TED group both on the 5th (p less than 0.01) and 10th (p less than 0.05) postoperative day. S-ASAT and S-gamma-GT increased significantly during heparin treatment, but did not differ significantly from the values of the TED group. No change in S-ALP was registered in either group. It is concluded that prophylactic treatment with low-dose heparin induces a significant increase in S-aminotransferase levels, especially in S-ALAT. The phenomenon has profound differential diagnostic implications in conditions such as pulmonary embolism and acute myocardial infarction.     

The clinical significance of serum and urinary neopterin levels in several renal diseases

Neopterin is a pyrazino-pyrimidine compound, and is known to be a marker associated with cell-mediated immunity in various diseases. We hypothesized that the levels of serum and urine neopterin would be elevated in renal disease, and would correlate with certain clinical parameters. We evaluated serum and urinary neopterin levels in patients with several renal diseases, including nephrotic syndrome (NS, n=19), chronic renal failure (CRF, n=8), end stage renal disease (ESRD, n=64) and controls (n=22). Serum neopterin was elevated in patients with CRF and ESRD, as compared to controls. Urinary neopterin levels were also found to be elevated in patients with CRF and ESRD, as compared to controls. Serum neopterin levels showed significant positive correlation with age, serum BUN and creatinine levels, and inverse correlation with WBC, hemoglobin, hematocrit, serum albumin and total iron binding capacity. Urine neopterin levels exhibited positive correlation with age and serum creatinine levels, and inverse correlation with WBC, hemoglobin, hematocrit, BUN and serum albumin. In conclusion, increased serum and urinary neopterin levels were found in some patients with renal disease and were correlated with certain clinical parameters.     

Genetic and clinical studies of serum beta 2-microglobulin levels in haematological malignancies.

Sera from 244 patients with haematological malignancies were examined for beta 2-microglobulin (beta 2m) levels. There were 142 leukaemias, 32 malignant lymphomas, three immunoblastic lymphomas, two pseudolymphomas and 65 multiple myelomas. Culture supernatants from various established cell lines were also tested. The phenotype facilitating beta 2m shedding from the cell surface appeared to be independent of the specific IgG heavy chain allotypes; however, a myeloma group with normal serum beta 2m levels showed a significant association with the specific Gm allotypes. The determination of serum beta 2m levels can provide valuable information on the proliferative stage of the disorders, the effectiveness of chemotherapy, and be a diagnostic aid for blastic crisis in chronic myelocytic leukaemias, and for subtyping lymphoid malignancies.     

The clinical utility of inhibiting CD28-mediated costimulation

Summary:  This volume covers many topics in the field of T-cell costimulation. The need for such a volume is testament to the growth of the field. From its beginning as a concept in the 1980s, we have now progressed to the point where many molecules now have functionally defined roles in T-cell costimulation. In addition, the field has progressed 'from bench to bedside'. Abatacept [cytotoxic T-lymphocyte antigen-4 (CTLA-4)-immunoglobulin (Ig) (CTLA-4-Ig)], an inhibitor of CD28-mediated T-cell costimulation, was approved for the treatment of moderate-to-severe rheumatoid arthritis in 2006 by the Food and Drug Administration and in 2007 by the European Medicines Agency. This chapter first presents a personal historical perspective on the early basic studies on the elucidation of the CD28/B7 T-cell costimulatory pathway and the discovery of CTLA-4-Ig. We next present an overview of studies of CTLA-4-Ig in preclinical animal studies. The material discussed in these first two sections is selective rather than exhaustive; their purpose is to provide context for the final section, a summary of human clinical studies performed with abatacept.     

The value of genetic testing: beyond clinical utility

ObjectiveTo assess the value of genetic testing from the perspective of the Department of Veterans Affairs (VA) clinical leadership.MethodsWe administered an Internet-based survey to VA clinical leaders nationwide. Respondents rated the value (on a 5-point scale) of each of six possible reasons for genetic testing. Bivariate and linear regressions identified associations between value ratings and environmental, organizational, provider, patient, and encounter characteristics.ResultsRespondents (n = 353; 63% response rate) represented 92% of VA medical centers. Tests that inform clinical management had the highest value rating (58.6%), followed by tests that inform disease prevention (56.4%), reproductive options (50.1%), life planning (43.9%), and a suspected (39.9%) or established (32.3%) diagnosis. Factors positively associated with high value included a culture that fosters adoption of genomics, specialist versus primary care provider, genetic tests available on laboratory menus, availability of genetic testing guidelines, clinicians knowing when to request genetics referrals, and availability of genetics professionals.ConclusionOur results demonstrate the varied value of genetic testing from the perspective of clinical leadership within a health-care system. Engaging organizational leadership in understanding the various reasons for genetic testing and its value beyond clinical utility may increase adoption of genetic tests to support patient-centered care.Genet Med advance online publication 15 December 2016     

血清肺炎衣原体抗体滴度水平对不稳定性心绞痛及其预后的临床预测价值

高血压、高胆固醇血症、吸烟和糖尿病等典型危险因素只能解释部分动脉粥样硬化性血管性疾病的流行病学特征 ,而在其中可能存在尚未被认知的其它因素。Ｎｉｅｍｉｎｅｎ等认为肺炎衣原体感染与冠心病有关 ,但对其间关系的临床价值尚未阐明。我们应用血清流行病学手段对国人冠心病不稳定性心绞痛病人 (ｕｎｓｔａｂｌｅａｎｇｉｎａｐｅｃｔｏｒｉｓ,ＵＡＰ)血清肺炎衣原体ＴＷＡＲＩｇＧ、ＩｇＭ滴度进行测定 ,探讨肺炎衣原体血清抗体滴度水平对ＵＡＰ及其预后的临床预测价值。材料和方法1　研究对象ＵＡＰ组 :连续入选 75例在青岛市市立医院…     

Reproductive functions of corticotropin-releasing hormone. Research and potential clinical utility of antalarmins (CRH receptor type 1 antagonists)

BACKGROUND: The hypothalamic-pituitary-adrenal (HPA) axis exerts a complex, mostly inhibitory, effect on the female reproductive system. In addition, the principal regulator of this axis, the hypothalamic neuropeptide corticotropin-releasing hormone (CRH) and its receptors have been identified in most female reproductive tissues, including the ovary, uterus, and placenta. Furthermore, CRH is secreted in peripheral inflammatory sites where it exerts strong inflammatory actions. Antalarmins (CRH receptor type 1 antagonists) have been used to elucidate the roles of CRH in stress, inflammation and reproduction. METHOD OF STUDY: We review existing data on the effects of CRH in the female reproductive system. RESULTS: Ovarian CRH participates in female sex steroid production, follicular maturation, ovulation and luteolysis. Uterine CRH participates in decidualization, implantation, and early maternal tolerance. Placental CRH participates in the physiology of pregnancy and the onset of parturition. Circulating placental CRH is secreted mostly during the latter half of pregnancy and is responsible for the concurrently increasing physiologic hypercortisolism of this period. After labor and delivery, this hypercortisolism is ensued by a transient suppression of hypothalamic CRH secretion, which may explain the postpartum blues and depression and the increased autoimmune manifestations depression of period, the postpartum period. CONCLUSIONS: These data show that CRH is present in female reproductive tissues, and is regulating key reproductive functions with an inflammatory component, such as ovulation, luteolysis, implantation, and parturition.     

乳腺癌术前及术后血清VEGF-C水平变化及临床意义

目的:探讨乳腺癌术前及术后血管内皮生长因子-C(VEGF-C)水平的变化及临床意义。方法:采用酶联免疫吸附法(ELISA)测定64例乳腺癌患者术前、术后血清VEGF-C水平的变化,并同时测定正常对照组30例血清VEGF-C的水平。结果:乳腺癌患者术后1个月血清VEGF-C的表达水平较术前比较,其表达水平明显下降,经统计学处理,差异有显著性(P0.01)。乳腺癌患者术前有转移组血清VEGF-C的表达水平明显高于无转移组(P0.01)。乳腺癌组术前血清VEGF-C的表达水平显著高于正常对照组(P0.01)。结论:VEGF-C在乳腺癌的发生发展中具有重要作用,血清VEGF-C的的表达水平高低可能与侵袭性的生物学行为有密切关系。     

Chromosomal changes in colorectal adenomas: relationship to gene mutations and potential for clinical utility

Although the occurrence of both chromosomal aberrations and specific gene mutations in colorectal tumorigenesis is firmly established, the relationship between these different forms of genetic abnormality remains poorly understood. We have previously demonstrated, in colorectal adenocarcinomas, that mutations of APC, KRAS, and TP53 are each specifically associated with certain chromosomal aberrations. Using comparative genomic hybridization and mutational analysis of APC, KRAS, and TP53 to evaluate 78 colorectal adenomas, we have shown that several of the significant relationships between gene mutations and chromosomal abnormalities reported in colorectal adenocarcinomas also exist at the adenomatous stage. KRAS mutation correlated with 12p gain (P < 0.001) and TP53 mutation with both 20q gain and 18q loss (P = 0.03 for both). In addition, we have identified two chromosomal aberrations, gain of 13q and loss of 11q, that correlate with the presence of synchronous adenomas (P = 0.049 and P = 0.03, respectively) and several chromosomal changes (20p+, 20q+, 17p-, and 18q-) that are related to the onset of high-grade dysplasia. These data strengthen our previous contention that the co-occurrence of specific gene mutations and chromosomal changes is not random and significant relationships do exist. Our findings also raise the possibility that certain chromosomal aberrations may act as important clinical biomarkers.