Prognostic value of quality-of-life scores in patients with breast cancer undergoing preoperative chemotherapy.

Background: Recently, evaluation of quality of life (QOL) has been recognized as a significant outcome measure in the treatment of several cancers. In this study, the Anti-Cancer Drugs-Breast (ACD-B) QOL score was used to assess disease-specific survival in women with breast cancer undergoing preoperative chemotherapy (POC). Methods: QOL-ACD-B scores were evaluated before and after POC. The cut-off value of QOL-ACD-B contributing to events such as relapse or death was calculated by receiver operating characteristic (ROC) curve analysis. Results: In 300 women with breast cancer treated with POC, QOL was significantly reduced (P < 0·001). A high QOL-ACD-B score before POC was an independent factor in the multivariable analysis of overall survival (hazard ratio 0·26, 95 per cent c.i. 0·04 to 0·96). Conclusion: Evaluation by QOL-ACD-B before POC may be useful to predict the prognosis of patients with breast cancer undergoing POC.

Alkaline extracellular conditions promote the proliferation and mineralization of a human cementoblast cell line.

AIM: To investigate the proliferation and mineralization of a human cementoblast cell line under alkaline conditions. METHODOLOGY: A human cementoblast cell line was cultured in alkaline media with several pHs (pH 7.6, 8.0 and 8.4) without CO2 . Cell numbers, phospho-p44/42 expression, alkaline phosphatase (ALP) activity and mineralization were evaluated. The significance of differences between groups was assessed using two-way analysis of variance 15 (ANOVA) followed by Bonferroni's multiple comparison test (α = 0.01). RESULTS: Cell numbers increased in a time-dependent manner in the high pH medium groups. Western blot analysis revealed the upregulated expression of phospho-p44/42 under alkaline conditions. ALP activity was also increased at pH 8.0 and 8.4. Alizarin red staining revealed increased mineralization in the high pH medium groups. The incorporation of the transient receptor potential ankyrin subfamily member 1 (TRPA1) antagonist HC030031 markedly negated the effect on proliferation and mineralization. CONCLUSIONS: Extracellular alkaline conditions promoted the proliferation and mineralization of human cementoblasts in vitro via TRPA1.

Correction to: Circulating tumor cell clusters-associated gene plakoglobin is a significant prognostic predictor in patients with breast cancer.

[This corrects the article DOI: 10.1186/s40364-017-0099-2.].

Tumour-infiltrating CD8 to FOXP3 lymphocyte ratio in predicting treatment responses to neoadjuvant chemotherapy of aggressive breast cancer.

BACKGROUND: Tumour-infiltrating lymphocytes (TILs) can be used to monitor the immune response, and are important in predicting treatment responses and outcomes for various types of cancer. Recently, specific TIL subsets have been reported to be clinically useful in predicting treatment responses. The CD8+/FOXP3+ TIL ratio (CFR) may be a more sensitive indicator for monitoring immune function. This study investigated the clinical significance and value of CFR as a biomarker to predict treatment responses to neoadjuvant chemotherapy for breast cancer. METHODS: Patients with resectable early-stage breast cancer treated with neoadjuvant chemotherapy at Osaka City University Hospital, Japan, between 2007 and 2013 were included. Oestrogen receptor, progesterone receptor, human epidermal growth factor receptor (HER) 2, Ki-67, CD8 and FOXP3 status were assessed by immunohistochemistry, and correlated with pathological complete response (pCR). RESULTS: A total of 177 patients were included, of whom 90 had a high CFR and 87 a low CFR. Triple-negative breast cancer (TNBC) was more common in the high-CFR group than in the low-CFR group (46 versus 23 per cent; P = 0·002), as was HER2-enriched breast cancer (HER2BC) (27 versus 14 per cent; P = 0·033). Among these patients, the pCR rate was significantly higher in the high-CFR group than in the low-CFR group (TNBC: P = 0·022; HER2BC: P < 0·001). In multivariable analysis high-CFR status was an independent predictor of a favourable prognosis: hazard ratio 0·24 (95 per cent c.i. 0·05 to 0·72; P = 0·015) for TNBC and 0·10 (0·10 to 0·90; P = 0·041) for HER2BC. CONCLUSION: The CFR may be a useful biomarker to predict treatment response to neoadjuvant therapy in aggressive breast cancer subtypes, such as TNBC and HER2BC.

Alginate encapsulant incorporating CXCL12 supports long-term allo- and xenoislet transplantation without systemic immune suppression.

Islet transplantation represents a potentially curative approach for individuals with Type I Diabetes. The requirement for systemic immune suppression to control immune-mediated rejection of transplanted islets and the limited human islet supply represent significant roadblocks to progress for this approach. Islet microencapsulation in alginate offers limited protection in the absence of systemic immunosuppression, but does not support long-term islet survival. The chemokine, CXCL12, can repel effector T cells while recruiting immune-suppressive regulatory T cells (Tregs) to an anatomic site while providing a prosurvival signal for beta-cells. We proposed that coating or encapsulating donor islets with CXCL12 would induce local immune-isolation and protect and support the function of an allo- or xenograft without systemic immune suppression. This study investigated the effect of alginate microcapsules incorporating CXCL12 on islet function. Islet transplantation was performed in murine models of insulin-dependent diabetes. Coating of islets with CXCL12 or microencapsulation of islets with alginate incorporating the chemokine, resulted in long-term allo- and xenoislet survival and function, as well as a selective increase in intragraft Tregs. These data support the use of CXCL12 as a coating or a component of an alginate encapsulant to induce sustained local immune-isolation for allo- or xenoislet transplantation without systemic immunosuppression.

c-Kit expression as a prognostic molecular marker in patients with basal-like breast cancer.

BACKGROUND: As patients with basal-like breast cancer (BLBC) have a poor prognosis and there is no specifically tailored therapy, molecular biological characterization of BLBC is necessary. c-Kit is a transmembrane receptor tyrosine kinase known to play important roles in various solid cancers. This study classified BLBCs from patients with breast carcinoma, and addressed the significance of c-Kit expression in these tumours. METHODS: Primary breast tumours were stained with antibodies against oestrogen receptor, progesterone receptor, human epidermal growth factor receptor (HER) 2, epidermal growth factor receptor (EGFR), cytokeratin 5/6 and c-Kit. The association between c-Kit, BLBC and survival was analysed. RESULTS: A total of 667 patients with breast cancer were followed up for a median of 39 (range 6-72) months. Some 190 tumours (28·5 per cent) were classified as triple-negative for breast cancer (negative for oestrogen receptor, progesterone receptor and HER2) and 149 (78·4 per cent) had characteristics of BLBC (positive for cytokeratin 5/6 and/or EGFR). c-Kit expression was detected in 111 (16·6 per cent) of 667 tumours. c-Kit-positive tumours were more commonly found among patients with BLBC (42 of 149, 28·2 per cent; P < 0·001) and in patients with nodal metastasis (47 of 216, 21·8 per cent; P = 0·014) than in those without. In patients with BLBC, the prognosis was significantly worse in those with c-Kit expression (P < 0·001). Multivariable logistic regression analysis revealed c-Kit as an independent negative prognostic factor for cancer-specific survival in patients with BLBC (hazard ratio 2·29, 95 per cent confidence interval 1·11 to 4·72). CONCLUSION: c-Kit might be a prognostic marker and possible molecular target for therapy in patients with BLBC.

Upregulation of cancer-associated myofibroblasts by TGF-ß from scirrhous gastric carcinoma cells.

BACKGROUND: Myofibroblasts in the cancer microenvironment have recently been implicated in tumour growth and metastasis of gastric cancer. However, the mechanisms responsible for the regulation of myofibroblasts in cancer-associated fibroblasts (CAFs) remain unclear. This study was performed to clarify the mechanisms for regulation of myofibroblasts in gastric cancer microenvironment. METHODS: Two CAFs (CaF-29 and CaF-33) from the tumoural gastric wall and a normal fibroblast (NF-29) from the nontumoural gastric wall, 4 human gastric cancer cell lines from scirrhous gastric cancer (OCUM-2MD3 and OCUM-12), and non-scirrhous gastric cancer (MKN-45 and MKN-74) were used. Immunofluorescence microscopy by triple-immunofluorescence labelling (α-SMA, vimentin, and DAPI) was performed to determine the presence of α-SMA-positive myofibroblasts. Real-time RT-PCR was performed to examine α-SMA mRNA expression. RESULTS: Immunofluorescence microscopy showed that the frequency of myofibroblasts in CaF-29 was greater than that in NF-29. The number of myofibroblasts in gastric fibroblasts gradually decreased with serial passages. Transforming growth factor-ß (TGF-ß) significantly increased the α-SMA expression level of CAFs. Conditioned medium from OCUM-2MD3 or OCUM-12 cells upregulated the α-SMA expression level of CAFs, but that from MKN-45 or MKN-74 cells did not. The α-SMA upregulation effect of conditioned medium from OCUM-2MD3 or OCUM-12 cells was significantly decreased by an anti-TGF-ß antibody or Smad2 siRNA. CONCLUSION: Transforming growth factor-ß from scirrhous gastric carcinoma cells upregulates the number of myofibroblasts in CAFs.

Significance of E-cadherin expression in triple-negative breast cancer.

PURPOSE: Triple-negative breast cancer (TNBC), a subtype of breast cancer that is oestrogen receptor (ER) negative, progesterone receptor (PR) negative, and human epidermal growth factor receptor 2 (HER2) negative, has a poor prognosis. Although a correlation between E-cadherin expression level and outcome has been demonstrated among all types of breast cancer, little is known about the significance of E-cadherin expression levels in TNBC. METHODS: A total of 574 patients who had undergone a resection of a primary breast cancer except for invasive lobular carcinomas were enrolled in this study. Expressions of ER, PR, HER2, and E-cadherin were assessed by immunohistochemistry. We examined the association between TNBC and other clinicopathological variables and evaluated the significance of the E-cadherin expression. RESULTS: Among the 574 breast cancer cases, 123 (21.4%) revealed a triple-negative phenotype. Patients with TNBC experienced more frequent lymph node metastasis (P=0.024) and a poorer prognosis (P<0.001) in comparison with non-TNBC patients. Triple-negative breast cancer was an independent prognostic factor. Reduced levels of E-cadherin were observed in 238 (41.5%) of the 574 breast cancer cases. E-cadherin reduction was significantly frequent in cases of TNBC (P<0.001) and lymph node metastasis (P=0.032). Furthermore, in the 123 TNBC cases, the prognosis of patients with an E-cadherin-negative expression was significantly worse than that of E-cadherin-positive patients (P=0.0265), especially for those in clinical stage II (P=0.002). A multivariate logistic regression analysis showed a reduction of the E-cadherin expression to be an independent prognostic factor (P=0.046). CONCLUSION: E-cadherin expression may be a useful prognostic marker for classifying subgroups of TNBC.

Establishment and characterization of a new hypoxia-resistant cancer cell line, OCUM-12/Hypo, derived from a scirrhous gastric carcinoma.

BACKGROUND: Many kinds of solid tumour have heterogeneously a hypoxic environment. Tumour hypoxia reported to be associated with more aggressive tumour phenotypes such as high metastatic ability and resistance to various anti-cancer therapies which may lead to a poorer prognosis. However, the mechanisms by which hypoxia affects the aggressive phenotypes remain unclear. METHODS: We established a scirrhous gastric carcinoma cell line (OCUM-12) from ascites associated with scirrhous gastric carcinoma, and a hypoxia-resistant cancer cell line (OCUM-12/Hypo) was cloned from OCUM-12 cells by continuous exposure to 1% oxygen. RESULTS: Histologic findings from orthotopic tumours derived from parent OCUM-12 cells and daughter OCUM-12/Hypo cells revealed poorly differentiated adenocarcinoma with extensive fibrosis that resembled human scirrhous gastric cancer. Necrotic lesions were frequently detected in the OCUM-12 tumours but were rarely found in the OCUM-12/Hypo tumours, although both types had multiple hypoxic loci. Apoptosis rate of OCUM-12 cells was increased to 24.7% at 1% O(2), whereas that of OCUM-12/Hypo was 5.6%. The OCUM-12/Hypo orthotopic models developed multiple metastases to the peritoneum and lymph nodes, but the OCUM-12 models did not. OCUM-12/Hypo cells showed epithelial-to-mesenchymal transition and high migratory and invasive activities in comparison with OCUM-12 cells. The mRNA expression levels of both E-cadherin and zonula occludens ZO-1 and ZO-2 decreased in OCUM-12/Hypo cells, and that of vimentin, Snail-1, Slug/Snail-2, Twist, ZEB-1, ZEB-2, matrix metalloproteinase-1 (MMP-1), and MMP-2 were increased in OCUM-12/Hypo cells. CONCLUSION: OCUM-12 and OCUM-12/Hypo may be useful for the elucidation of disease progression associated with scirrhous gastric cancer in the setting of chronic hypoxia.

Dynamic behavior of individual cells in developing organotypic brain slices revealed by the photoconvertable protein Kaede.

In recent years, advances in optical imaging methods have facilitated the visualization of events in the developing cortex. In particular, the introduction of DNA encoding fluorescent protein into cells of the embryonic brain allows the visualization of progenitor cells; slice preparations of the cortex then allow the monitoring of the behavior of transfected cells in the context of the living cerebral wall by time-lapse microscopy. Such approaches have provided substantial information about the patterns of neuronal migration. However, as these techniques label large numbers of cells in the ventricular zone (VZ), it is difficult to follow individual cell shape changes or cell behaviors within the VZ, where neuron production and initial migration take place. Here, we report a unique method using the photoconvertable fluorescent protein Kaede, which emits green fluorescence and shifts to emitting red fluorescence upon radiation with UV. Using this method, we were able to follow the behavior of a particular pair of daughter cells among neighboring Kaede-positive cells in the SVZ of mouse brain slices. The spindle shape progenitor divided into two multipolar-shaped daughter cells. The cell-cell borders of daughter cells were clearly visualized, and easily describe the position and distance between two or more cells. The photoconvertable property of Kaede offers a powerful cell marking tool to identify the precise morphology and migratory behaviors of individual cells within living cortical slices.

The free-radical scavenger, edaravone, augments NO release from vascular cells and platelets after laser-induced, acute endothelial injury in vivo.

In vitro and in vivo experimental models have demonstrated that vascular endothelial function is significantly impaired as a result of oxidative stress, mediated by the generation of oxygen-derived free radicals in response to chronic or acute inflammation. In particular, super-oxide () at specific concentrations leads to the impairment of nitric oxide (NO) bioactivity, and it is known that NO plays a fundamental role in the maintenance of vascular homeostasis. The relationship between reactive oxygen species (ROS) and NO release in thrombosis-related endothelial damage in the peripheral microvasculature remains unclear, however. The purpose of the present study was to investigate the effect of the free-radical scavenger, edaravone, on NO synthesis and thrombotic potential in arterioles after exposure to laser irradiation. Highly sensitive electrochemical NO microsensors were positioned in femoral arterioles of mice, and the kinetics of NO release were recorded in response to standardized laser irradiation in vivo. In addition, images of NO release from damaged vascular cells were investigated in a similar rat model using the NO-sensitive dye 4,5-diaminofluorescein diacetate (DAF-2DA). Thrombogenesis was assessed in carotid arterioles by continuous video microscopy using image analysis software. Laser irradiation led to NO release from perturbed endothelial cells and from platelet-rich thrombi. Edaravone had no significant effect on NO release in non-laser treated, intact endothelium compared with placebo. In contrast, edaravone demonstrated a dose-dependent effect on NO release and thrombogenicity. At a concentration of 10.5 mg/kg per h, edaravone promoted a 5-fold increase in NO and a reduction in platelet-rich thrombus volume to 58% of the placebo values. Our data provide direct evidence to confirm that acute endothelial damage in peripheral microvessels initially induces NO release and that the free-radical scavenger, edaravone, augments NO synthesis leading to suppression of platelet thrombus formation.

Construction of a self-cloning sake yeast that overexpresses alcohol acetyltransferase gene by a two-step gene replacement protocol.

The commercial application of genetically modified industrial microorganisms has been problematic due to public concerns. We constructed a "self-cloning" sake yeast strain that overexpresses the ATF1 gene encoding alcohol acetyltransferase, to improve the flavor profile of Japanese sake. A constitutive yeast overexpression promoter, TDH3p, derived from the glyceraldehyde-3-phosphate dehydrogenase gene from sake yeast was fused to ATF1; and the 5' upstream non-coding sequence of ATF1 was further fused to TDH3p-ATF1. The fragment was placed on a binary vector, pGG119, containing a drug-resistance marker for transformation and a counter-selection marker for excision of unwanted DNA. The plasmid was integrated into the ATF1 locus of a sake yeast strain. This integration constructed tandem repeats of ATF1 and TDH3p-ATF1 sequences, between which the plasmid was inserted. Loss of the plasmid, which occurs through homologous recombination between either the TDH3p downstream ATF1 repeats or the TDH3p upstream repeat sequences, was selected by growing transformants on counter-selective medium. Recombination between the downstream repeats led to reversion to a wild type strain, but that between the upstream repeats resulted in a strain that possessed TDH3p-ATF1 without the extraneous DNA sequences. The self-cloning TDH3p-ATF1 yeast strain produced a higher amount of isoamyl acetate. This is the first expression-controlled self-cloning industrial yeast.

Age-related accumulation of Ig V(H) gene somatic mutations in peripheral B cells from aged humans.

To investigate age-related alterations in human humoral immunity, we analysed Ig heavy chain variable region genes expressed by peripheral B cells from young and aged individuals. Three hundred and twenty-seven cDNA sequences, 163 micro and 164 gamma transcripts with VH5 family genes, were analysed for somatic hypermutation and VHDJH recombinational features. Unmutated and mutated micro transcripts were interpreted as being from naive and memory IgM B cells, respectively. In young and aged individuals, the percentages of naive IgM among total micro transcripts were 39% and 42%, respectively. D and JH segment usage in naive IgM from aged individuals was similar to that from young individuals. The mutational frequencies of memory IgM were similar in young and aged individuals. gamma transcripts, which are regarded as being from memory IgG B cells, showed a significantly higher mutational frequency (7.6%) in aged than in young individuals (5.8%) (P < 0.01). These findings suggest that VHDJH recombinational diversity was preserved, but that the accumulation of somatic mutations in the IgG VH region was increased in aged humans. The accumulation of somatic mutations in IgG B cells during ageing may imply that an age-related alteration exists in the selection and/or maintenance of peripheral memory B cells.

The effectiveness of anti-retroviral drug therapy for HIV-1 is associated with HIV-1 proviral DNA levels and viral selection.

The effect of combination anti-retroviral therapy regimens on HIV-1 proviral DNA levels in peripheral blood mononuclear cells was examined in 12 HIV-1-positive patients, using endpoint dilution polymerase chain reaction and serial cloning, and sequencing of the gag region of HIV-1. The major clone was defined as the most numerous of 10 analysed clones, and observation periods ranged from 8 months to 32 months (mean 19.7 +/- 10.2 months). In five patients (one with primary-stage HIV-1 infection) receiving three anti-retroviral drugs, HIV-1 RNA reduced to undetectable levels (i.e. < or = 100 copies/ml). HIV-1 proviral DNA and the number of major clones reduced in four of these patients. HIV-1 RNA levels reduced, but remained detectable, in five other patients. In the two remaining patients (both receiving two rather than three anti-retroviral drugs), HIV-1 RNA levels increased. These results suggest that the population of major clones may be affected when HIV-1 RNA levels reduce following combination regimens of anti-retroviral therapy.

Extremely low vertical-emittance beam in the accelerator test facility at KEK.

Electron beams with the lowest, normalized transverse emittance recorded so far were produced and confirmed in single-bunch-mode operation of the Accelerator Test Facility at KEK. We established a tuning method of the damping ring which achieves a small vertical dispersion and small x-y orbit coupling. The vertical emittance was less than 1% of the horizontal emittance. At the zero-intensity limit, the vertical normalized emittance was less than 2.8 x 10(-8) rad m at beam energy 1.3 GeV. At high intensity, strong effects of intrabeam scattering were observed, which had been expected in view of the extremely high particle density due to the small transverse emittance.

A reduction in the number of peripheral CD28+CD8+T cells in the acute phase of influenza.

Influenza patients show a high incidence of T lymphocytopenia in the acute phase of the illness. Since CD8+ T cells play an important role in influenza virus infection, we investigated which subset of CD8+ T cells was involved in this lymphocytopenia. CD8+ T cells from eight patients with influenza A were studied for lymphocyte count, surface marker, and intracellular IFN-gamma production in the acute (days 1-3) and recovery phases (days 9-12). Total and T lymphocyte counts in the acute phase were approximately three times less than in the recovery phase; however, the CD4/8 ratio was the same in both phases. The cell count reduction in the acute phase was attributed predominantly to the CD28+ CD8+ subset, compared with the CD28- CD8+ subset. The memory/activation marker CD45RO on the CD8+ T cells was assessed. The CD28+ CD45RO- subset, a naive phenotype, was reduced significantly in number in the acute phase compared with the recovery phase. The CD28+ CD45RO+ subset, a memory phenotype, was also reduced in the acute phase, but the reduction was not statistically significant. Intracellular IFN-gamma in the CD8+ subset after mitogenic stimulation was measured by flow cytometry; the percentage of CD28+ IFN-gamma-/CD8+ subset in the acute phase was significantly less than in the recovery phase. These results indicated that the predominant reduction of peripheral CD8+ T cells in the acute phase of influenza was from naive-type lymphocytes, suggesting that these quantitative and qualitative changes of CD8+ T cells in influenza are important for understanding the immunological pathogenesis.

Evidence of B cell clonal expansion in HIV type 1-infected patients.

HIV-1 infection results in a gradual decrease in CD4(+) T cell counts and progressive immune deficiency. Increased T cell turnover in HIV-1-infected patients, which can be interpreted as T cell clonal expansion, has been thought to be relevant to its pathogenesis. To investigate whether B cell clonal expansion also occurs in HIV-1-infected patients, we examined the expressed V(H)DJ(H) gene sequences of peripheral B cells in HIV-1-infected patients with hypergammaglobulinemia. Identical V(H)DJ(H) gene rearrangements with additional nucleotide differences in V(H) genes were analyzed as a marker of clonally related B cells. From healthy individuals and HIV-1-uninfected patients with hypergammaglobulinemia, clonally related B cells were detected in none of 10 (0%) and 2 of 10 (20%), respectively. No clonally related B cells were detected in any of the nine HIV-1-infected patients with detectable viral loads and normal Ig levels (0%). In contrast, from 9 of 14 HIV-1-infected patients with hypergammaglobulinemia (64%), clonally related B cells were detected. In addition, no HIV-1-infected patients who exhibited normal Ig levels after antiretroviral therapy had clonally related B cells. These findings suggest that B cell clonal expansion is present in HIV-1-infected patients with hypergammaglobulinemia.

Human T lymphotropic virus type 1 infection influences hepatitis C virus clearance.

To explore the effect of human T lymphotropic virus type 1 (HTLV-1) infection on hepatitis C virus (HCV) infection, a survey for these viral infections was conducted that involved 2280 residents in an area in which HTLV-1 and HCV are endemic. The response of patients with HCV and HTLV-1 to interferon (IFN)-alpha treatment was also assessed. Antibody to HCV was detected in 13.8% of the residents tested, and antibody to HTLV-1 was detected in 15.4%. The prevalence of HCV RNA was significantly higher among residents who had antibodies to both HCV and HTLV-1 than in those who had antibodies to HCV only (P<.05). Sustained elimination of HCV RNA by IFN was significantly more frequent among patients with HCV alone than among those with HCV and HTLV-1. By logistic regression analysis, HTLV-1 infection was associated with nonresponse to IFN treatment. Thus, HTLV-1 infection affects the clearance, both natural and in association with IFN treatment, of HCV.

Hepatitis B virus genomes of chronic hepatitis patients do not contain specific mutations related to acute exacerbation.

To determine the specific viral variants associated with acute exacerbation of chronic hepatitis from hepatitis B virus (HBV) infection, we analyzed the complete nucleotide sequences of the HBV genome in serial serum samples from two chronic active hepatitis patients who seroconverted from HBeAg to anti-HBe. HBV DNA was amplified by polymerase chain reaction (PCR) and sequenced. A 1896 precore stop codon mutant (G to A at nt 1896) coexisting with the wild sequence was found in both patients prior to seroconversion from HBeAg to anti-HBe. Core promoter mutations at nucleotide positions 1762 (A to T) and 1764 (G to A) were found in both patients throughout the observation period. Mutations were observed in the HBV genome of the two patients at different time points, and there was no correlation between the mutations and liver disease or DNA polymerase levels. The nucleotide divergence rate and the composition of quasispecies in the HBV sequence at the time of acute exacerbation were almost the same as were found at other time points. These results suggest that acute exacerbation does not appear to be caused by a characteristic HBV species. The multiple factors that cause generalized HBV replication activation may contribute to acute exacerbation.

[Effect of highly active antiretroviral therapy (HAART) on hypergammaglobulinemia in HIV infected patients].

To investigate the mechanism of hypergammaglobulinemia in HIV infected patients, the effect of highly active antiretroviral therapy (HAART) on the hypergammaglobulinemia was analyzed. Involved in this study were 34 untreated, 21 HAART-effective (complete response) and 14 HAART-non-effective (partial response) patients. Serum levels of HIV-RNA and gammaglobulin and immunoglobulin (Ig) isotypes were measured. Mean HIV-RNA levels of untreated and partial response patients were 1.6 x 10(4) copies/ml and 0.4 x 10(4) copies/ml, respectively. HIV-RNA levels of all complete response patients were below 4.0 x 10(2) copies/ml. Mean gammaglobulin percentages of untreated, partial response and complete response patients were 24.4%, 21.8% and 17.9%, respectively (p < 0.01 in untreated vs complete response patients). Mean IgG levels in the three groups were 2,489 mg/dl, 1,947 mg/dl and 1,618 mg/dl, respectively (p < 0.001 in untreated vs complete response patients). IgA levels were high in some untreated patients and lower in complete response patients. IgE levels were increased in some untreated and partial response patients, but there was no significant difference among the three groups. These results suggested that the hypergammaglobulinemia found in HIV infected patients was associated with HIV replication. The activation mechanism might differ by Ig isotypes.