Luteinizing hormone (LH) formed a complex with an immunoglobulin G caused abnormally high levels of LH: A case report.

We encountered a 30-year-old woman with remarkably elevated luteinizing hormone (LH) levels, as measured by electrochemiluminescent immunoassay (ECLIA), and no specific symptoms. We performed the following investigations: dilution linearity test, polyethylene glycol (PEG) precipitation test, immunoprecipitation test, protein G addition test, and high-performance liquid chromatography (HPLC) analysis. The linearity of patient's serum was similar to that of a standard LH preparation, and non-specific reactions were not observed. The recovery rate of LH shown by the PEG precipitation test, immunoprecipitation test, and protein G addition test was low. Moreover, an abnormal peak in HPLC was located at a slightly larger molecular weight position than that of IgG. These results showed the presence of macro-LH, LH, and anti-LH-IgG autoantibody complex and suggested that the clearance of LH from the blood was delayed due to IgG binding, and therefore, the LH value was falsely high. We should keep the possibility of macro-LH in mind in cases of unexpectedly high LH values.

[The Study of a New Formula for Correcting Serum Calcium Levels, Considering the Difference in Albumin Analysis Methods].

In Japan, Payne's formula [corrected Ca=total Ca+ (4-ALB)] has been used to correct serum calcium concentration levels. However, the current methods for measuring calcium and albumin differ from those that were used to establish the Payne's formula. For albumin measurement, particularly, values differ be- tween BCG and improved BCP method. In 2014, Ohba et al. reported a modified formula [corrected Ca= total Ca+0.7X (4-ALB)], which is more suitable for correcting calcium with the improved BCP method than with the Payne's method. In the same year, the recommendation for converting albumin concentration with the improved BCP method to that with the BCG method was presented by the Japanese Society of La- boratory Medicine. Thus, we conceived a new modified formula [corrected Ca=total Ca+ {4- (BCP+ 0.3) }], which is included in the contents of this recommendation, and examined the effects of this formula in comparison with the Payne and Ohba methods. The patients recruited for the calcium adjustment were as follows: (i) all patients; (ii) patients with albumin concentrations <4.0 g/dL; and (iii) patients with albumin concentrations ≤3.5 g/dL. Payne's formula overcorrected calcium with the improved BCP method. Ohba's method was suitable for (i), while the new for- mula was specifically more suitable for (iii) than the Payne and Ohba formulas. The present study showed that our new formula is more suitable for calcium adjustment in patients with albumin concentrations ≤3.5 g/dL. [Original].

Protein kinase C ζ regulates survivin expression and inhibits apoptosis in colon cancer.

The phosphatidylinositol 3-kinase pathway transduces cell survival signals in different malignancies. Protein kinase C ζ (PKCζ) is one of the molecules involved in this pathway. In this study, we investigated the role of PKCζ in apoptosis. Short interfering RNA against PKCζ (siPKCζ) sensitized HCT116 and SW480 colon cancer cells to TRAIL­induced apoptosis. Among anti-apoptotic proteins, survivin protein and mRNA expression levels decreased after siPKCζ transfection while protein half-life did not change. The expression levels of survivin and PKCζ were correlated in 18 colon cancer specimens (r=0.72, P=3.01x10­4). Chemosensitivity to 5-FU was enhanced by siPKCζ in HCT116 and SW480 cells. These results indicate that PKCζ regulates survivin expression levels and inhibits apoptosis in colon cancer cells. This study provides a rationale for targeting PKCζ in combination with chemotherapy for colon cancer treatment.

High prevalence of human anti-mouse antibodies in the serum of colorectal cancer patients.

BACKGROUND: Monoclonal antibody treatment induces the expression of human anti-mouse antibodies (HAMA), which in turn interfere with the therapy. However, whether HAMAs are expressed before the initiation of antibody therapy in patients with colorectal cancer remains unknown. MATERIALS AND METHODS: Serum samples were collected from 40 patients diagnosed with colorectal cancer. Serum samples from 157 individuals without cancer were used as controls. None of the patients received imaging or therapeutic antibodies before the study. The expression of HAMAs was evaluated by ELISA with murine immunoglobulin G1 (mIgG)1, mIgG2a and mIgG2b as the antigen. RESULTS: Of the 40 colorectal cancer patients, 9 (22.5%) expressed either IgG- or IgM-type HAMAs while only 13/157 (8.2%) of the individuals without cancer expressed the HAMAs (p<0.05). CONCLUSION: HAMAs are prevalent in the serum of colorectal cancer patients even before antibody administration. Medical practitioners should be alert to the possibility of HAMA expression when administering antibody therapy.

Evaluating the utility of N1,N12-diacetylspermine and N1,N8-diacetylspermidine in urine as tumor markers for breast and colorectal cancers.

BACKGROUND: Among natural polyamines, the concentrations of the diacetylated form of spermine and spermidine increase in the urine of patients with cancer. We evaluated the utility of urinary N(1),N(12)-diacetylspermine (DiAcSpm) and N(1),N(8)-diacetylspermidine (DiAcSpd) as tumor markers for breast and colorectal cancers. METHODS: Urinary DiAcSpm and DiAcSpd concentrations were measured by an enzyme-linked immunosorbent assay. Urine and serum samples were collected from 33 and 28 patients with colorectal and breast cancers, respectively. The sensitivity of urine samples to DiAcSpm and DiAcSpd concentrations was compared with serum concentrations of carcinoembryonic antigen (CEA) and carbohydrate antigen CA 15-3 in breast cancer patients and with serum concentrations of CEA and CA 19-9 in colorectal cancer patients, respectively. RESULTS: In breast cancer patients, the sensitivity of DiAcSpm and DiAcSpd was 46.4% and 14.2%, respectively, which was higher than that of CEA and CA 15-3. In patients with colorectal cancer, the sensitivity of DiAcSpm and DiAcSpd was 69.6% and 36.3%, respectively. CEA was the second sensitive marker and CA 19-9 was the least sensitive marker in these patients. CONCLUSION: DiAcSpm is a highly sensitive tumor marker. DiAcSpm can serve as a powerful tool in settings such as initial screening for cancers in routine health examination.

Polymorphism of Clara cell 10-kD protein gene of sarcoidosis.

Clara cell 10-kD protein (CC10) exhibits potent antiinflammatory properties. G38A polymorphism was found in the CC10 gene. We investigated the genetic influence of the allele on the development of sarcoidosis using case control analysis in a Japanese population (265 sarcoidosis cases and 258 control subjects). The A allele frequency in sarcoidosis cases (45.1%) was significantly higher than healthy control subjects (34.9%, p = 0.0002). According to outcomes, we divided 223 patients with follow-up periods of 3 years or more into two subgroups (55 progressive and 168 regressive disease). The A allele frequency in patients with progressive disease was significantly higher than control subjects (odds ratio = 4.55; 95% confidence interval, 2.97-6.97; p < 0.0001), whereas that of regressive disease was not. The A/A genotypes had significantly lower bronchoalveolar lavage fluid CC10 levels than the G/G (nonsmokers, p = 0.0054, and smokers, p = 0.0045) and G/A genotypes (nonsmokers, p = 0.0022, and smokers, p = 0.0402). The reporter gene assay showed significantly lower reporter activities in the presence of interferon-gamma for the 38A construct than the 38G construct (p = 0.0177). The G38A polymorphism in the CC10 gene may influence protein expression and be associated with the development of progressive sarcoidosis.