Plasma soluble HLA-G is a potential biomarker for diagnosis of colorectal, gastric, esophageal and lung cancer

Human leukocyte antigen-G (HLA-G) is a novel tumor marker and its soluble isoforms produce secretory proteins. Increased soluble HLA-G (sHLA-G) levels have been reported in patients with melanoma, neuroblastoma, lymphoproliferative disorders, breast, ovarian and colorectal carcinoma when compared to healthy controls or subjects with benign neoplasms. The aim of this study is to investigate whether or not plasma sHLA-G can be used as a potential biomarker for cancer diagnosis. We measured plasma sHLA-G levels in 166 patients with early stages of colorectal cancer (CRC, n = 37), gastric cancer (GC, n = 28), esophageal squamous cell carcinoma (ESCC, n = 58) and non-small cell lung cancer (NSCLC, n = 43), and compared them to healthy controls (n = 260) by using a specific HLA-G enzyme-linked immunosorbent assay (ELISA). We found that plasma sHLA-G levels were significantly higher in cancer patients than in healthy controls (all P < 0.0001). The areas under the receiver-operating characteristic (ROC) curves for sHLA-G were 0.97, 0.91, 0.98 and 0.80 for healthy controls vs CRC, GC, ESCC and NSCLC, respectively. At 100% specificity, the highest sensitivity achieved to detect CRC, GC, ESCC and NSCLC was 94% [95% confidence interval (CI), 89-99], 85% (95% CI, 76-94), 91% (95% CI, 88-94) and 51% (95% CI, 43-59) at a cutoff value of 49 U/ml, respectively. These findings suggest that plasma sHLA-G may be a useful molecule in the differential diagnosis of these malignancies against healthy controls.     

Comparison of sleep-disordered breathing among healthy elderly in the seventh, eighth, and ninth decades of life

We investigated the prevalence of sleep-disordered breathing (SDB) in healthy 80 year-old subjects (n = 38) as compared with healthy 70-(n = 33) and 60-year-old subjects (n = 34). The apnea-hypopnea index (AHI) increased significantly across decades: 39.5% (15 of 38) of 80 year olds, 33.3% (11 of 33) of 70 year olds, and 2.9% (1 of 34) of 60 year olds had an AHI greater than or equal to 5 (chi 2 = 14.0, p less than 0.001). The prevalence of SDB as measured by a more stringent apnea index criterion of greater than or equal to 5 was 18.9% of those in their 80s, 12.1% in their 70s, and 0% in their 60s (chi 2 = 6.63, p less than 0.05). Significant gender differences were noted in the proportion of subjects with AHI greater than or equal to 10: 22.4% of men versus 5.4% of women (chi 2 = 4.25, p less than 0.05). These data suggest that SDB increases with advancing age even in the healthy elderly and may be more marked in healthy men than women.     

The immunogenicity and safety of an investigational meningococcal serogroups A, C, W-135, Y tetanus toxoid conjugate vaccine (ACWY-TT) compared with a licensed meningococcal tetravalent polysaccharide vaccine: A randomized, controlled non-inferiority study

Immunogenicity and safety of ACWY-TT compared with licensed ACWY polysaccharide vaccine (MenPS) in healthy adults, and lot-to-lot consistency of three ACWY-TT lots were evaluated in a phase 3, open, controlled study. Adults aged 18-55 y were randomized to receive ACWY-TT (one of three lots) or MenPS. Serum bactericidal antibodies (rSBA) were measured pre- and 1 mo post-vaccination. Adverse events (AEs) were assessed 4 d (solicited symptoms) and 31 d (unsolicited symptoms) post-vaccination. Serious AEs were reported up to 6 mo after vaccination. The number of vaccinated subjects was 1247 (ACWY-TT, n = 935; MenPS, n = 312). ACWY-TT lot-to-lot consistency and non-inferiority of ACWY-TT as compared with MenPS groups were demonstrated according to pre-specified criteria. The percentages of subjects with a vaccine response (VR = rSBA titer ≥ 1:32 in initially seronegative; ≥ 4-fold increase in initially seropositive) to ACWY-TT vs. MenPS were 80.1%/69.8% (serogroup A), 91.5%/ 92.0% (C), 90.2%/85.5% (W-135), 87.0%/78.8% (Y). Exploratory analyses showed that for serogroups A, W-135 and Y, VR rates and GMTs were significantly higher for ACWY-TT compared with MenPS. For each serogroup, ≥ 98.0% of subjects had rSBA titers ≥ 1:128. Grade 3 solicited AEs were reported in ≤ 1.6% of subjects in any group. The immunogenicity of ACWY-TT vaccine was non-inferior to MenPS for all four serogroups in adults, with significantly higher VR rates to serogroups A, W-135 and Y and an acceptable safety profile. Consistency of 3 ACWY-TT production lots was demonstrated. These data suggest that, if licensed, ACWY-TT conjugate vaccine may be used for protection against invasive meningococcal disease in healthy adults. This study is registered at clinicaltrials.gov NCT00453986.     

Simple and objective method for routine detection of the macular pigment xanthophyll

A new simple method for two-dimensional determination of optical density of macular pigment xanthophyll (ODx) in clinical routine is based on a single blue-reflection fundus image. Individual different vignetting is corrected by a shading function. For its construction, nodes are automatically found in structureless image regions. The influence of stray light in elderly crystalline lenses is compensated by a correction function that depends on age. The reproducibility of parameters in a one-wavelength reflection method determined for three subjects (47, 61, and 78 years old) was: maxODx = 6.3%, meanODx = 4.6%, volume = 6%, and area = 6% already before stray-light correction. ODx was comparable in pseudophakic and in an eye with a crystalline lens of the same 11 subjects after stray-light correction. Significant correlation in ODx was found between the one-wavelength reflection method and the two-wavelength autofluorescence method for pseudophakic and cataract eyes of 19 patients suffering from dry age-related macular degeneration (AMD) (R(2) = 0.855). In pseudophakic eyes, maxODx was significantly lower for dry AMD (n = 45) (ODx = 0.491±0.102 ODU) than in eyes with healthy fundus (n = 22) (ODx = 0.615±0.103 ODU) (p = 0.000033). Also in eyes with crystalline lens, maxODx was lower in AMD (n = 125) (ODx = 0.610±0.093 ODU) than in healthy subjects (n = 45) (ODx = 0.674±0.098 ODU) (p = 0.00019). No dependence on age was found in the pseudophakic eyes both of healthy subjects and AMD patients.     

Population survey of CCR5 delta32, CCR5 m303, CCR2b 64I,and SDF1 3'A allele frequencies in indigenous Chinese healthy individuals,and in HIV-1-infected and HIV-1-uninfected individuals in HIV-1 risk groups

The aim of this study is to determine in indigenous Chinese ethnic groups the frequencies of the chemokine (SDF1 3'A) and chemokine receptors (CCR5 delta32, CCR5 m303, and CCR2b 64I) HIV-1/AIDS restriction alleles. The study includes two cohorts; the first comprised 3165 indigenous healthy subjects representing eight ethnic groups: Han (n = 1406), Uygur (n = 316), Mongolia (n = 134), Hui (n = 386), Tibetan (n = 330), Zhuang (n = 378), Dai (n = 101), and Jingbo (n =114). The second cohort consisted of 330 HIV-1-infected (86 subjects infected by sexual transmission and 198 subjects infected by HIV-1-contaminated blood or by sharing injection equipment; the remaining 46 subjects said nothing about HIV-1 transmission) and 474 HIV-1-uninfected Han Chinese belonging to one of two HIV-1 high-risk groups: intravenous drug users (n = 215) and individuals with sexually transmitted diseases (n = 259). Genotypes for the four genes were obtained using PCR (CCR5 delta32) or PCR-restriction fragment length polymorphism. Randomly selected amplified PCR products were further confirmed by direct DNA sequencing. The variant allele frequencies were determined to be 0% to 3.48% for CCR5 delta32, 0% for CCR5 m303, 16.23% to 28.79% for CCR2b 64I, and 17.70% to 27.76% for SDF1 3'A in Chinese healthy individuals from eight ethnic groups. These findings show that allele frequencies differ among the eight Chinese ethnic groups for CCR5 delta32, CCR2b 64I, and SDF1 3'A and that the CCR5 m303 and CCR5 delta32 mutant alleles were absent or infrequent in Chinese, which may be helpful for studies of specific anti-HIV-1 vaccine trials and coreceptor inhibitor drug targets in Chinese populations. Furthermore, we observed no significant differences in allele or genotypic frequencies between HIV-1-infected and HIV-1-uninfected groups from the Han ethnic group. Our finding is the first reporting that there is likely no effect of the examined polymorphisms in our study on HIV-1 transmission in the Chinese Han population, However, the genetic effects of these and other AIDS-modifying polymorphisms on the pathogenesis and clinical outcome of HIV-1/AIDS diseases is under investigation in Chinese populations.     

c-erb-B_2、P_(53)癌基因蛋白在消化道癌症中的表达及其与癌组织微血管周围纤维连接蛋白的关系

用免疫组织化学标记法测定27例消化道癌症病人c-erb-B_2、P_(53)癌基因蛋白的表达。胃癌组(n=17)c-erb-B_2阳性率为70.59％,炎症溃疡对照组(n=9),阳性率为44.44％,健康人组(n=4)阳性率为0％。胃癌转移组(n=6)P_(53)表达的阳性率(0％)比胃癌无转移组(n=11)阳性率(54.55％)明显降低(P<0.05)。在两种癌基因的联合表达上,以c-erb-B_2( )P_(53)(-)组最多(52.94％)。6例有转移的胃癌中癌组织间质微血管周围的Fn免疫荧光明显减弱,与c-erb-B_2表达间呈明显负相关(r=-0.8728,P<0.05)。重点讨论了上述变化与胃癌间的可能关系。     

T cell activation, apoptosis and cytokine dysregulation in the (co)pathogenesis of HIV and pulmonary tuberculosis (TB)

Immune parameters were compared in four groups of Ugandan subjects: HIV-and HIV+ adult patients with active pulmonary TB (HIV- PTB n = 38; HIV+ PTB n = 28), patients with HIV infection only (n = 26) and PPD+ healthy controls (n = 25). Compared with healthy controls, CD4 and CD8 T cells from patients with HIV and/or PTB expressed more activation markers (HLA-DR, CD38); their CD8 T cells expressed more CD95 (pre-apoptosis) and less CD28 (co-stimulatory receptor). Peripheral blood mononuclear cells (PBMC) of patients with either HIV or PTB were impaired in interferon-gamma (IFN-gamma) production upon antigenic stimulation. PTB (with or without HIV) was characterized by monocytosis, granulocytosis, increased transforming growth factor-beta 1 production and PPD-induced apoptosis. In vivo CD4 T cell depletion, in vitro increased spontaneous CD4 T cell apoptosis and defects in IFN-gamma responses upon mitogenic stimulation were restricted to HIV+ subjects (with or without PTB). Overlapping and distinctive immune alterations, associated with PTB and HIV, might explain mutual unfavourable influences of both diseases.     

Use of two sensitive and specific immunoblot markers, em70 and em90, for diagnosis of alveolar echinococcosis

Antibodies against Echinococcus multilocularis metacestodes were screened by immunoblotting sera from patients with alveolar echinococcosis (n = 39), cystic echinococcosis (n = 109), or other parasitic infections (n = 66) and healthy individuals (n = 32). Two antigens, approximately 70 and 90 kDa, are found to be valuable for confirmatory diagnosis, with a sensitivity and specificity of 100 and 99.51%, respectively.     

A breath-holding challenge in panic disorder patients,their healthy first-degree relatives,and normal controls

Our aim was to observe the induction of panic attacks (PA) symptoms by a breath-hold test in panic disorder (PD) patients as the Diagnostic and Statistical Manual for Mental Disorders 4th edition (DSM-IV) and their healthy first-degree relatives. We randomly selected 26 PD patients, 28 healthy first-degree relatives of probands with PD and 25 normal volunteers with no family history of PD. They were induced to breath-hold for as long as possible four times with a two-min interval between them. Anxiety scales were applied before and after the test. Using specific PA criteria, 46.1% (n=12) PD patients, 7.1% (n=2) first-degree relatives and 4.0% (n=1) control subjects had a PA after the test (chi(2)=7.82, df=2, P=0.023). There was no heart rate, anxiety levels or breath-hold time differences among the groups. In this breath hold challenge test PD patients were more sensitive to breath-hold than first-degree relatives and normal volunteers.     

Reticulocyte maturity as an indicator for estimating qualitative abnormality of erythropoiesis.

AIMS--To determine the maturity of reticulocytes in patients with anaemia as a result of various haematological disorders including those with qualitative abnormalities such as ineffective erythropoiesis or dyserythropoiesis. METHODS--The number of mature reticulocytes was measured with flow cytometry in venous blood samples from 122 patients with haematological disorders and 100 healthy controls. Reticulocytes were classified into three categories by the fluorescence intensity of auramin O staining: low fluorescence ratio (LFR), medium fluorescence ratio (MFR), and high fluorescence ratio (HFR). Immature reticulocytes were determined as the aggregate of MFR and HFR (%). RESULTS--The mean (2SD) number of immature reticulocytes in 100 normal subjects was 9.0 (7.0)%. Significantly high mean values of immature reticulocytes with a normal or reduced reticulocyte count were shown in 90 patients with dyserythropoietic or ineffective erythropoietic conditions, such as acute myeloid leukaemia (AML) (n = 37), myelodysplastic syndrome (MDS) (n = 35), aplastic anaemia (AA) (n = 8), or megaloblastic anaemia (MA), (n = 6). Reticulocyte ratios returned to normal after successful treatment of patients with AML (n = 10) and MA (n = 3). However, high percentages of immature reticulocytes with increased reticulocyte counts were consistently observed in patients with enhanced erythropoiesis such as those with acquired autoimmune haemolytic anaemias (AIHA) (n = 4) or acute blood loss (ABL) (n = 4). Reticulocyte maturity was within the normal range in patients with reduced erythropoiesis such as occurs in chronic renal failure (CRF) (n = 11), or in iron deficiency anaemia (IDA) (n = 13). CONCLUSIONS--The evaluation of reticulocyte maturity with total reticulocyte count seems to be clinically useful for estimating the qualitative impairment of erythropoiesis, and so could help differentiate haematological disorders.     

Search for association between suicide attempt and serotonergic polymorphisms

Serotonergic neurotransmission has been implicated in suicidal behavior. Polymorphisms in the genes coding for tryptophan hydroxylase, serotonin receptor 2A and serotonin transporter were investigated in a sample of suicide attempters (n = 165) and healthy control subjects (n = 99). No significant differences were found for any of the investigated polymorphisms. Neither did any significant differences emerge in comparison with control subjects when the suicide attempters were grouped into different diagnostic categories: unipolar disorder (n = 45), adjustment disorder (n = 37), substance use disorder (n = 37) and personality disorder, cluster B (n = 36). The results suggest that alleles defined by the investigated polymorphisms do not represent a major determinant in suicide attempt. However, a highly significant (P = 0.001; odds ratio, 1.47; 99% confidence interval, 1.42-1.53) allelic association between tryptophan hydroxylase and suicide attempt is indicated after pooling our data with literature data. In light of previous data, a possible association between the tryptophan hydroxylase polymorphism and a phenotype that may become differently stratified within differently selected samples of suicide attempters is discussed.     

Support for an association between HLA-DR1 and schizophrenia in the Japanese population

An increase of HLA-DR1 has been observed in schizophrenia patients from the Japanese population. A decrease of DR4, which was reported in Caucasian patients, has also been found in some of the Japanese studies. This small study further investigated frequencies of HLA-DR1 and DR4 in unrelated Japanese patients with schizophrenia (n = 45) and healthy comparison subjects (n = 117). The number of patients possessing DR1 was higher (10 of 45, 22%) compared with the comparison group (11 of 117, 9.4%, P = 0.03). This may support the previous observation of an increased DR1 frequency in the Japanese patients. When the present data is combined with three previous studies, proportions of the Japanese subjects with DR1 were 98 of 588 schizophrenia patients (16.7%) vs. 93 of 942 comparison subjects (9.9%). However, no difference was observed in DR4 frequencies between the patients (51%) and comparison subjects (44%). Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:725-727, 2000.     

Identification, diagnostic potential, and natural expression of immunodominant seroreactive peptides encoded by five Mycobacterium tuberculosis-specific genomic regions

Comparative genomic studies have identified several Mycobacterium tuberculosis-specific genomic regions of difference (RDs) which are absent in the vaccine strains of Mycobacterium bovis BCG and which may be useful in the specific diagnosis of tuberculosis (TB). In this study, a total of 775 synthetic peptides covering the sequences of 39 open reading frame (ORF) proteins encoded by genes predicted in five RDs of M. tuberculosis, i.e., RD1, RD4, RD5, RD6, and RD7, were tested by enzyme-linked immunosorbent assays for antibody reactivity with sera from HIV-negative pulmonary TB patients (n = 100) and M. bovis BCG-vaccinated healthy subjects (n = 100). The results identified three immunodominant peptides reactive with TB sera, i.e., amino acids (aa) 346 to 370 of RD1ORF Rv3876, aa 241 to 265 of RD6ORF Rv1508c, and aa 325 to 336 of RD6ORF Rv1516c. These peptides had significantly stronger antibody reactivity with sera from TB patients than with sera from healthy subjects (P < 0.05) and significantly higher rates of positivity with TB sera (positives = 66 to 93%) than sera from healthy subjects (positives = 10 to 28%). Antipeptide antibodies were raised in rabbits after immunization with pools of 11 peptides corresponding to each protein. Probing of culture filtrates and whole-cell lysates of M. tuberculosis with antipeptide antibodies suggested the natural expression of Rv1516c in whole-cell lysates of M. tuberculosis. The results suggest the potential of the identified immunodominant RD peptides in the serodiagnosis of TB.     

Identification and Characterization of a Novel, 37-Kilodalton Leishmania donovani antigen for diagnosis of Indian visceral leishmaniasis

The biggest challenge in the serological diagnosis of visceral leishmaniasis (VL) is to find a biomarker with a high specificity. This study was undertaken to identify novel Leishmania donovani antigens to solve the existing problem. The soluble L. donovani promastigote antigen was separated by SDS-PAGE, and a Western blot was probed with pooled sera of five subjects with confirmed VL before (n = 9 pools) and after (n = 9 pools) treatment and at the 6-month follow-up visit (n = 9 pools), healthy controls not from an area of endemicity (n = 9 pools), and healthy controls from an area of endemicity. The antibody response to the identified partially purified antigen was ascertained by an enzyme-linked immunosorbent assay (ELISA) with 70 sera from patients with parasitologically confirmed VL, 48 sera from healthy controls from an area where the disease is not endemic, 60 sera from healthy controls from an area of endemicity, and 42 sera from patients in different disease groups. The eluted protein was subjected to two-dimensional (2D) gel electrophoresis, Western blotted, and probed with sera from patients with confirmed VL and from healthy controls not from an area of endemicity. The antigenic protein was further characterized by matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry. The identified protein (BHUP2) corresponds to a cytochrome c-like synthesis protein of 37 kDa. ELISA results were 94% sensitive, whereas specificities with sera from healthy controls from an area of endemicity, healthy controls not from an area of endemicity, and disease controls were 98%, 100%, and 97%, respectively. The antigen identified via a proteomics-based approach has a strong potential for further development as a diagnostic tool for VL.     

Human herpesvirus type 8 in patients with cirrhosis: correlation with sex, alcoholism, hepatitis B virus, disease severity, and thrombocytopenia

Immunologic abnormalities in patients with cirrhosis strongly correlate with severity of liver cirrhosis. The association between cirrhosis and human herpesvirus type 8 (HHV-8) infection is unclear. Plasma samples were obtained from 74 healthy control subjects and 59 patients with cirrhosis. The seropositive rates for HHV-8 antibodies in patients with cirrhosis (25/59 [42%]) were significantly higher than that in healthy control subjects (18/74 [24%]; P = .027), particularly in men (P = .027), patients with alcohol-related cirrhosis (P = .032), and patients with thrombocytopenia (P = .019) or Child-Pugh class C cirrhosis (P = .018) or both (P = .015), or hepatitis B virus (HBV) infection (P = .003). Antibody titers in seropositive patients also significantly exceeded those in healthy control subjects (P = .008). All subjects were negative for anti-HIV. In Taiwan, cirrhosis is associated with HHV-8 infection, particularly in men, patients with Child-Pugh class C cirrhosis and/or thrombocytopenia, and patients with alcohol- or HBV-related cirrhosis.     

Comparison of airway conductance and FEV(1) as measures of airway responsiveness to methacholine. Discrimination of small differences in bronchial responsiveness with Gaw and FEV(1).

When defining bronchial responsiveness in healthy, non-asthmatic, subjects exposed in different working situations, it is not clear whether different outcome measures yield similar results. Therefore, the concentration and dose of methacholine that caused a 20% decrease in forced expiratory volume in 1 s (FEV(1)) (PC20(FEV(1)) and PD20(FEV(1))), the corresponding change in Gaw and the relationship between the dose-response slope (DRS) for FEV(1) and Gaw was studied in different working populations and healthy control subjects (n=1038). The two outcome measures were compared in groups of subjects in whom differences in bronchial responsiveness could be anticipated [atopics (n=72) and non-atopics (n= 207) and subjects exposed (n=54) and not exposed (n=32) to saw dust]. A bronchial challenge was also made before and after exposure in a swine confinement building, an exposure known to increase bronchial responsiveness (n=37). PD20(FEV(1)) was 1.7 mg in atopics and 4.9 mg in non-atopics, 7.1 mg in saw dust exposed and >20 mg in non-exposed subjects and 5.3 mg before and 0.79 mg after exposure to organic dust. There was a correlation between DRS(FEV(1)) and DRS(Gaw), r=0.87 (P<0.001). In subjects who were highly sensitive to methacholine a 20% change in FEV(1) corresponded to <40% change in Gaw, while a 20% decrease in FEV1 corresponded to none or a minor decrease in Gaw in subjects with less methacholine-sensitive airways. The ability to detect differences in bronchial responsiveness between groups, or to detect changes in bronchial responsiveness following exposure was approximately the same for FEV(1) and Gaw. The reproducibility was similar for both variables and a second measurement was within one doubling of the methacholine concentration of the first provocation in approximately 95% of all measurements (n=41). In conclusion, with our methacholine provocation method, FEV(1) and Gaw had similar sensitivity in detecting small differences in bronchial responsiveness in healthy subjects.     

Support for an association between HLA‐DR1 and schizophrenia in the Japanese population

An increase of HLA‐DR1 has been observed in schizophrenia patients from the Japanese population. A decrease of DR4, which was reported in Caucasian patients, has also been found in some of the Japanese studies. This small study further investigated frequencies of HLA‐DR1 and DR4 in unrelated Japanese patients with schizophrenia (n = 45) and healthy comparison subjects (n = 117). The number of patients possessing DR1 was higher (10 of 45, 22%) compared with the comparison group (11 of 117, 9.4%, P = 0.03). This may support the previous observation of an increased DR1 frequency in the Japanese patients. When the present data is combined with three previous studies, proportions of the Japanese subjects with DR1 were 98 of 588 schizophrenia patients (16.7%) vs. 93 of 942 comparison subjects (9.9%). However, no difference was observed in DR4 frequencies between the patients (51%) and comparison subjects (44%). Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:725–727, 2000. © 2000 Wiley‐Liss, Inc.     

Carriage frequency, intensity of carriage, and strains of oral yeast species vary in the progression to oral candidiasis in human immunodeficiency virus-positive individuals

Candida samples were taken over a period of 2 years from 54 human immunodeficiency virus (HIV)-positive asymptomatic subjects to evaluate changes in yeast carriage, intensity of carriage, and genotype over time. Overall, we found that HIV-positive patients with CD4(+)-cell counts of between 200 and 400/microl had significantly more yeast colonization than healthy control subjects. Of the 54 patients, 11 developed thrush. We found that intensity of carriage in these 11 patients increased significantly in the progression from asymptomatic yeast carrier to an episode of oral thrush. Also, the most common yeast species isolated was Candida albicans; however, we did see a number of patients harboring multiple species at the same time. Using the C. albicans-specific probe Ca3, we found that 54% (n = 6) of the 11 patients who developed thrush maintained genetically similar strains throughout the study period, with minor genetic variations in all patients except one. Forty-six percent of these patients had either multiple strains throughout the study period (n = 2), strain replacement (n = 1), or species replacement (n = 2). Of the patients who had multiple strains, one (I4) was infected by two different strains of Candida dubliniensis distinguished by a recently developed species-specific probe. These results suggest that commensal strains colonizing HIV-positive individuals can undergo alterations prior to producing an episode of thrush.     

Dysregulation of beta-chemokines in the lungs of HIV-1-infected patients

The beta-chemokines, macrophage inflammatory protein (MIP)-1 alpha, MIP-1 beta, monocyte chemotactic protein (MCP)-1 and regulated-on-activation normal T cell, expressed and secreted (RANTES) are not only chemotactic for mononuclear cells but may be important in suppression of HIV-1 replication through competitive binding to the chemokine receptor, CCR5, which is critical to viral entry. In this study, bronchoalveolar cells (BACs) and autologous peripheral blood mononuclear cells (PBMCs) were obtained from HIV-1-infected participants who did not manifest clinical signs of lung disease with peripheral CD4 T-cell count >200/mm(3) (n = 7, group with high CD4 count), or CD4 T-cell count <200/mm(3) (n = 12, group with low CD4 count), and from healthy study subjects (n = 5). The capacity to express beta-chemokines and CCR5 was assessed. Induction of MIP-1 alpha by lipopolysaccharide (LPS) in BAC of HIV-1-infected study subjects from the low CD4 group was less than BAC from healthy study subjects (p <.001), and also was less than in BACs from the group with a high CD4 group (p <.001). Moreover, the intracellular expression of MIP-1 alpha in LPS-induced monocytes of HIV-1-infected patients was significantly less than that from healthy study subjects (p <.01). In addition, spontaneous expression of mRNAs for CCR5 and MIP-1 alpha in BAC was significantly lower in HIV-1-infected patients compared with in healthy study subjects (p <.03 and p <.02, respectively). In contrast to the findings with MIP-1 alpha, LPS stimulated MCP-1 in BAC from the group of HIV-1-infected patients with high CD4 count was significantly higher than healthy study subjects (p <.001). These dysregulations in the ability to express beta-chemokines by BAC may be important in the progression of HIV-1 infection in the lung.     

Sensitivity, specificity, and predictive value of serum soluble transferrin receptor at different stages of iron deficiency

This study investigated the efficiency of serum soluble transferrin receptor (sTfR) for assessing body iron status at different stages of iron deficiency. Among 72 patients with advanced iron-deficiency anemia (IDA), the sensitivity and specificity of sTfR (at a diagnostic cutoff of 3.24 mg/L) were 70.8% and 90.6%, respectively, with a positive predictive value of 85.0%. Sensitivities of sTfR in patients at the earliest stage of iron deficiency (n=41) and the intermediate stage of iron-deficient erythropoiesis (n=15) were 21.9% and 26.7%, respectively, at the same cutoff value of sTfR. Serum ferritin concentrations averaged 6.7+/-1.9 microg/L in IDA patients with sTfR <3.24 mg/L, which were significantly above the values in IDA patients with sTfR >or=3.24 mg/L (4.8+/-1.2 microg/L, p<0.05). In healthy controls, blood reticulocyte counts were significantly higher in subjects with sTfR >or=3.24 mg/L than in those with sTfR <3.24 mg/L (0.045+/- 0.013 (10(12)/L) vs 0.034+/- 0.011 (10(12)/L), p<0.05]. In conclusion, sTfR level is not a sensitive indicator for the early or intermediate stages of iron deficiency, although sTfR assay can be a useful aid in the diagnosis of advanced IDA. Serum sTfR concentration has significant relationships with blood reticulocyte counts in healthy subjects and with serum ferritin levels in IDA patients.