<Superscript>1</Superscript>H-NMR metabonomics analysis of sera differentiates between mammary tumor-bearing mice and healthy controls

Global analysis of ¹H-NMR spectra of serum is an appealing approach for the rapid detection of cancer. To evaluate the usefulness of this method in distinguishing between mammary tumor-bearing mice and healthy controls, we conducted ¹H-NMR metabonomic analyses on serum samples obtained from the following: 10 mice inoculated with a highly-metastatic mammary carcinoma cell line, 10 mice inoculated with a “normally” metastatic mammary carcinoma cell line, and 10 healthy controls. Following standard spectral processing and subsequent data reduction, we applied unsupervised Principal Component Analysis (PCA) to determine if unique metabolic fingerprints for different categories of metastatic breast cancer in serum exist. The PCA method correctly separated sera of tumor-bearing mice from that of normal healthy controls, as shown using the scores plot which indicated that sera classes from tumor-bearing mice did not share multivariate space with that from healthy controls. In addition, this technique was capable of distinguishing between classes of varying metastatic ability in this system. Metabolites apparently responsible for separation between diseased and healthy mice include lactate, taurine, choline, and sugar moieties. Results of this study suggest that ¹H-NMR spectra of mouse serum analyzed using PCA statistical methods indicate separation of tumor-bearing mice from healthy normal controls, justifying further study of the use of ¹H-NMR metabonomics for cancer detection using serum.     

Dermatoglyphics in patients with hypothyreosis

About 15% of all females and 3% of all males suffers from hypothyreosis. The thyroid disease is the most frequent cause of hypothyreosis, and among people in Croatia who are suffering from that disease 90% have been affected by its autoimmune form. The thyroid diseases are supposed to be caused by the influence of various genetic and external factors and some forms of genetic influences have not yet been studied. Analysis of digito-palmar dermatoglyphics has been used in the research of the role of genetic predisposition in many various diseases. We have analyzed correlation of qualitative and quantitative traits between the group of 50 females suffering from hypothyreosis and a control group of 100 phenotypically healthy females. Quantitative statistical analysis using t-test has indicated only few significantly different variables, while the discriminant analysis has shown 76.9% correctly classified samples. The factor analysis has shown a high percentage of total variance within patients suffering from hypothyreosis, as well as the different structure of individual factors. Qualitative analysis has shown the heterogeneity between the two examined groups. The results of the research have proved that the qualitative characteristics are more unstable than the quantitative ones and they have also shown the instability of genes taking part in hypothyreosis development implying genetic predisposition of the disease.     

Quantitative dermatoglyphics in males and females of five Sardinian linguistic groups

Discriminant analysis of 23 digital and 15 palmar quantitative dermatoglyphic variables of 1364 Sardinians, 689 males and 675 females, were performed to identify biological relationships among five Sardinian linguistic groups of both sexes. By ANOVA 17 of the 23 digital variables and 4 of the 15 palmar variables were significantly different among males and females of the Sardinian linguistic groups. By MANOVA the results indicate high intergroup heterogeneity also within each sex. By stepwise discriminant analysis with p≤0.01 as F-to-enter and p≤0.05 as F-to-remove, only 4 of the 38 digital and palmar variables were in the model (URC R5, RRC L5, RRC R5, URC R4). The pattern of interpopulation biological relationships shows a clearly distinct position of the Gallurian group (both males and females) which speaks an Italian dialect. The properly Sardinian linguistic groups (Campidanian and Logudorian), the Sassarian group (which speaks and Italian dialect) and the Alghero group (which speaks Catalan) were close to one another. This pattern agrees more with the ethno-historical background than with the linguistic one.     

Decreased binding of [11C]NNC112 and [11C]SCH23390 in patients with chronic schizophrenia

AimsAbnormality of cognitive function in schizophrenia has been suggested to be related to dopamine D₁ receptor. However, the results of previous positron emission tomography (PET) studies of dopamine D₁ receptor in schizophrenia were not consistent.Main methodsIn this study, six patients with schizophrenia in severe residual phase with chronic antipsychotic treatment and twelve healthy age-matched controls participated. Two different radioligands, [¹¹C]NNC112 and [¹¹C]SCH23390, for dopamine D₁ receptor were used on the same subjects. Binding of the ligands was measured by PET, and statistical analysis was performed using one-way analysis of covariate (ANCOVA) with age as covariate.Key findingsGood correlations between binding potential values (BP_ND) and age were observed in all regions of interest (ROIs) with both ligands. ANCOVA with age as covariate of BP_ND values of all ROIs revealed that the patient group showed significantly lower BP_ND value compared with the control group in both ligands.SignificanceIn patients with chronic schizophrenia in severe residual phase with chronic antipsychotic treatment, the binding potential values of both ligands were significantly lower in the striatum and cortical regions than those of healthy controls.     

Studies on acute human infections using FTIR microspectroscopy and cluster analysis

A novel methodology for the diagnosis of acute infections using FTIR microspectroscopy (FTIR-MSP) data on blood components and cluster analysis is presented. Blood samples were collected from 11 patients suffering from various infections and 16 age-matched healthy human controls. Blood components such as white blood cells, red blood cells, and plasma were isolated using standard procedures and FTIR-MSP of these components was utilized. A cluster analysis of the FTIR spectra was performed. The spectra obtained from the three blood components of patients were different from those of controls. The FTIR spectra of white blood cells from patients suffering infections were significantly different from the controls. Cluster analyses of averaged FTIR-MSP spectra of white blood cells provided 100% classification between patients and healthy controls.     

Interleukin-10 and interleukin-18 promoter polymorphisms in an Italian cohort of patients with undifferentiated carcinoma of nasopharyngeal type

Purpose: Cytokines such as IL-10 and IL-18 seem to be involved in the inflammatory response of undifferentiated carcinoma of nasopharyngeal type (UCNT). The aim of this study was to evaluate the correlation between functional single nucleotide polymorphisms (SNPs) in the promoter region of IL-10 and IL-18 genes and the virological and clinical characteristics in a large case series of Caucasian patients suffering from UCNT, a tumor regularly associated with the Epstein Barr Virus (EBV). Methods: Eighty-nine patients with histologically confirmed UCNT and 130 healthy donors were included in our study. DNA was examined for the polymorphisms of IL-10 gene at positions –1082, −819, −592 by direct sequencing and IL-18 gene at position −607 and −137 by allele –specific PCR. EBV DNA serum viremia was evaluated by QC-PCR. Results: The distributions of the IL-10 and IL-18 genetic variants were not different between UCNT patients and healthy controls. The frequency of IL-10 –1082G allele, which is associated with high IL-10 expression, showed a nearly statistically significant increase in UCNT patients EBV DNA-negative as compared to healthy controls (OR=3.3 95% CI: 1.2–9.8). Subjects with C/C or C/G combined IL-18 genotypes showed an increased risk of being with Stages III-IV (OR=2.1 95% CI: 1.2–6.6). Conclusion: This study was performed to improve the definition of the pathogenetic factors implicated in UCNT by addressing the correlation between cytokine polymorphisms and clinical parameters. This is the first study investigating the possible role of the IL-18 and IL-10 polymorphisms in the development and outcome of UCNT. In our genetic analysis there is no evidence for involvement of IL-10 promoter polymorphisms alone in the genetic predisposition to this tumor. On the other hand, IL18 genetic variants may represent a genetic risk factor for tumor aggressiveness.     

肺癌患者血清CEA、CYFRA21-1和NSE的检测及临床意义

目的探讨外周血癌胚抗原(CEA)、细胞角蛋白19片段(CYFRA21-1)和神经元特异性烯醇化酶(NSE)的检测对肺癌的诊断、病理分型和疗效判断的临床用价值。方法采用化学发光法检测了62例肺癌患者、54例良性肺部疾病患者、36例健康人、40例肺癌患者手术前后血清CEA、CYFRA21-1和NSE的水平。结果肺癌患者手术前血清CEA、CYFRA21-1和NSE的含量明显高于良性肺部疾病组及正常对照组(P0.01)。鳞癌组、腺癌组和小细胞癌组之间肿瘤标志物CEA、CYFRA21-1和NSE水平差异有统计学意义。CEA阳性率以腺癌组最高(84%),CYFRA21-1阳性率以鳞癌组最高(85.2%),NSE阳性率以小细胞癌组最高(80.0%)。手术治疗后未复发转移组CEA、CYFRA21-1和NSE水平低于术前,而复发转移组与术前比变化不显著(P0.05)。结论血清CEA、CYFRA21-1和NSE的检测对不同病理类型肺癌患者的诊断、病情检测及疗效判断有较好的临床参考价值。     

Electromyographic patterns of individuals suffering from lateral tennis elbow.

This study investigated the applicability of using surface electromyography (EMG) as a tool for differentiating between persons suffering from lateral tennis elbow and the healthy age-matched adults. Temporal muscle activation patterns of the tennis elbow group were evaluated to determine if they varied between subject groups and if noted variations might be interpreted as arresting or exacerbating the injury. Sixteen subjects (Healthy Controls, n = 6; Tennis Elbow, n = 10) were tested under simulated tennis playing conditions. All subjects were males (Healthy group (CON) 38.8 +/- 13.1, Injured group (INJ) 40.8 +/- 10.8 yrs). EMG response data, temporal and spatial muscle activities, of the forearm extensors (Ext), the forearm flexors (Flex) and the triceps (Tri) were recorded for each subject during a single test session using all combinations of three different velocities on three different racket head impact locations. Data were collected at a frequency of 1000 Hz. Statistical analysis was performed using a 2 x 3 x 3 (Health status x Impact velocity x Impact location) ANOVA with repeated measures. Results indicated statistically significant differences (p < 0.05) between the CON and INJ subject groups for the response variables associated with forearm extensor muscle activation. During simulated play, the INJ group employed an earlier, longer, and greater activation of Ext than the CON group, such changes may be considered detrimental to the healing process. These results support the use of surface EMG to quantify differences in muscle activation strategies employed by individuals suffering from soft tissue muscle microtrauma injuries and healthy controls.     

Blood groups in relation to carcinoma of cervix uteri.

Data are presented on AB0 and RhD blood groups in 186 patients suffering from carcinoma of cervix uteri and 274 controls from Delhi, India. A strong association is observed between carcinoma patients and blood group A, and a slightly weaker association with blood group B. There is no significant association with RhD blood group. The available data in other populations confirm the association with AB0 blood group.     

Neurophysins as markers of vasopressin and oxytocin release. A study in carcinoma of the lung

Vasopressin-neurophysin (hNpI), oxytocin-neurophysin (hNpII) and blood osmolality were assayed before any treatment in basal conditions in 35 patients suffering from lung carcinoma (20 oat cell, 6 undifferentiated and 9 well-differentiated epidermoid cell carcinomas). Plasma vasopressin (antidiuretic hormone, ADH) was also assayed in 7 of the 20 patients suffering from oat cell carcinoma. We found a close correlation (r = 0.98) between plasma ADH and hNpI levels in the 7 patients. Further, hNpI was elevated in 13 out of the 20 oat cell carcinoma patients and in none of the epidermoid-cell carcinoma group; however, searching for an abnormality of ADH secretion as reflected by a detectable plasma hNpI level together with subnormal plasma osmolality revealed 2 additional positive results in the oat cell carcinoma group, and 2 out of the 6 in the undifferentiated-cell carcinoma group. hNpII was increased together with an increase in hNpI in 6 oat cell carcinoma patients; it was specifically increased without hNpI increment in 2 additional oat cell carcinoma patients and in 2 patients of the undifferentiated-cell carcinoma group (different from the 2 positive for the hNpI-osmolality ratio). hNpI and hNpII were normal in the majority of undifferentiated and all of the differentiated epidermoid-cell carcinoma group. Hence, our results show that simultaneous measurements of hNpI, hNpII, and blood osmolality could detect abnormalities in 17 out of 20 oat cell carcinoma patients, in 4 of the 9 undifferentiated-cell carcinoma patients, but in none of the differentiated epidermoid-cell carcinoma patients, suggesting that the neurophysin assay can be used for the early detection of oat cell- and possibly other neuroendocrine-derived carcinomas.     

Allergic Patients with Long-Term Asthma Display Low Levels of Bifidobacterium adolescentis

Accumulated evidence suggests a relationship between specific allergic processes, such as atopic eczema in children, and an aberrant fecal microbiota. However, little is known about the complete microbiota profile of adult individuals suffering from asthma. We determined the fecal microbiota in 21 adult patients suffering allergic asthma (age 39.43 ± 10.98 years old) and compare it with the fecal microbiota of 22 healthy controls (age 39.29 ± 9.21 years old) using culture independent techniques. An Ion-Torrent 16S rRNA gene-based amplification and sequencing protocol was used to determine the fecal microbiota profile of the individuals. Sequence microbiota analysis showed that the microbial alpha-diversity was not significantly different between healthy and allergic individuals and no clear clustering of the samples was obtained using an unsupervised principal component analysis. However, the analysis of specific bacterial groups allowed us to detect significantly lower levels of bifidobacteria in patients with long-term asthma. Also, in allergic individuals the Bifidobacterium adolescentis species prevailed within the bifidobacterial population. The reduction in the levels on bifidobacteria in patients with long-term asthma suggests a new target in allergy research and opens possibilities for the therapeutic modulation of the gut microbiota in this group of patients.     

Type 1 Diabetic Serum Interferes with Pancreatic β-cell Ca2+ -Handling

The aim of this study was to clarify the frequency of patients with type 1 diabetes that have serum that increases pancreatic β-cell cytoplasmic free Ca²⁺ concentration, [Ca²⁺]_i, and if such an effect is also present in serum from first-degree relatives. We also studied a possible link between the serum effect and ethnic background as well as presence of autoantibodies. Sera obtained from three different countries were investigated as follows: 82 Swedish Caucasians with newly diagnosed type 1 diabetes, 56 Americans with different duration of type 1 diabetes, 117 American first-degree relatives of type 1 diabetic patients with a mixed ethnic background and 31 Caucasian Finnish children with newly diagnosed type 1 diabetes. Changes in [Ca²⁺]_i , upon depolarization, were measured in β-cells incubated overnight with sera from type 1 diabetic patients, first-degree relatives or healthy controls. Our data show that there is a group constituting approximately 30% of type 1 diabetic patients of different gender, age, ethnic background and duration of the disease, as well as first-degree relatives of type 1 diabetic patients, that have sera that interfere with pancreatic β-cell Ca²⁺-handling. This effect on β-cell [Ca²⁺]_i could not be correlated to the presence of autoantibodies. In a defined subgroup of patients with type 1 diabetes and first-degree relatives a defect Ca²⁺-handling may aggravate development of β-cell destruction.     

Study on the association of p53 codon 72 polymorphisms with risk of gastric cancer in high incidence Hexi area of Gansu Province in China

To investigate the possible association of P53 codon 72 Arg/Pro polymorphisms with risk of gastric cancer in the high incidence Hexi area of Gansu province in China. Blood samples from 140 patients with gastric carcinoma and 125 healthy controls were collected in Hexi area of Gansu province. Polymorphism of P53Arg72Pro was genotyped by PCR-TaqMan. For detection Helicobacter pylori infection, Warhin–Starry staining was used. Three kinds of polymorphisms of P53Arg72Pro were Arg/Arg, Arg/Pro, Pro/Pro. The frequencies in gastric cancer group were 15.7, 60.0, 24.3%, and the frequencies in healthy controls were 25.6, 54.4, 20.0%, respectively. P53 codon 72 Pro carrier genotype (Arg/Pro + Pro/Pro) increased risk of gastric carcinoma with an odds ratio 1.840 (95% CI: 1.006–3.387). Helicobacter pylori infection rate was 68.6% in patients group and 50.4% in healthy controls. Helicobacter pylori infection rate in gastric cancer patients was remarkably higher than that in the controls (OR: 2.147, 95% CI: 1.302–3.541, P = 0.003). Stratification analysis showed that P53 codon 72 Pro carrier genotype with Helicobacter pylori infection was significantly higher in cases than that in the controls (OR: 4.182, 95% CI: 1.850–9.454). P53Arg72Pro polymorphisms could be a risk factor for gastric cancer in high incidence Hexi area of Gansu Province in China. P53 codon 72 Pro carrier genotype and Helicobacter pylori positive infection may have a synergistic effect on gastric cancer in high incidence Hexi area of Gansu Province in China.     

Urinary zinc excretion is normalized in primary arterial hypertension after perindopril treatment

Increased or unchanged urinary zinc excretion has been reported in hypertension. In the present article, this observation was confirmed in a group of 10 untreated hypertensive patients of both sexes that had no diabetes or obesity. The 24-h zinc excretion was significantly different between the patients: 7.46±3.01 μmol and healthy controls: 5.19±2.19 μmol (p<0.025). After a 1-mo treatment with 4 mg perindopril per day, a decrease of urinary zinc was observed until it reached levels not significantly different from those of the healthy controls (5.98±2.13 μmol). The decrease was significantly different from that of the pretreatment values (p<0.05).     

Lead,copper, zinc,and magnesium levels in hair of children and young people with some disorders of the osteomuscular articular system

The lead, copper, zinc, and magnesium contents of scalp hair taken from 173 children aged 1–15 yr and young people (16–18 yr) with certain disorders of the osteomuscular articular system (osteomuscular pains of unknown origin, once described as “growing pains”) were measured, using the flame atomic absorption spectrometry method, and then compared with those of 108 normal, healthy children. The research showed increased average levels of lead (a statistically significant p<0.05 in both the overall group of children, and in those over 11 yr old), and zinc (increased in the total group, in a statistically significant way at p<0.10 only in adolescents over 15 yr old) and decreased levels of copper (although not significantly) in the hair of children suffering from “rheumatic” diseases, as compared with controls. The magnesium levels for the total group of ill children were admittedly enhanced, but in the youngest children, the levels were reduced. The values of the Mg/Pb and Mg/Zn ratios were lower (in the youngest children, 70% decrease of the Mg/Pb ratio) and Zn/Cu were higher in the group of children suffering from rheumatic diseases than in the healthy children. The difference of Mg/Pb ratio between the total controls and rheumatic subjects was statistically significant at p<0.05 and the Zn/Cu at p<0.10. The Mg/Zn ratio was not statistically significant.     

Quantitative dermatoglyphic asymmetry: a comparative study between schizophrenic patients and control groups of West Bengal, India

Quantitative Fluctuating (FA) and Directional asymmetry (DA) of dermatoglyphics on digito-palmar complex were analyzed in a group of 111 patients (males: 61, females: 50) with schizophrenia (SZ), and compared to an ethnically matched phenotypically healthy control (males: 60, females: 60) through MANOVA, ANOVA and canonical Discriminant analyses. With few exceptions, asymmetries are higher among patients, and this is more prominent in FA than DA. Statistically significant differences were observed between patient and control groups, especially in males. In both sexes, FA of combined dermatoglyphic traits (e.g. total finger ridge count, total palmar pattern ridge count) are found to be a strong discriminator between the two groups with a correct classification of over 83% probability.     

Lymphocytotoxic antibodies in cancer

Summary To study the relationship of cold-reactive lymphocytotoxic antibodies (LCA) to immune defects in cancer, LCA were measured in sera from 71 patients with different types of malignancies and 31 healthy controls. A significantly increased incidence (10 of 24) of LCA was noted in a group of patients with lymphoreticular malignancies excluding chronic lymphocytic leukemia (CLL). No significantly increased incidence of LCA was found in patients with CLL (0 of 9), melanoma (5 of 22), or carcinoma (1 of 16) as opposed to normal controls (1 of 31). In the lymphoreticular malignancy group, no correlation was noted between LCA levels and delayed hypersensitivity skin tests, skin croton oil response, total lymphocytes, T cells, or B cells. We conclude that LCA is increased in patients with certain lymphoreticular malignancies in contrast to other types of cancer. Its presence, however, is unrelated to major defects in the cell-mediated immune system seen in some of these patients.     

Study of peripheral blood lymphocyte subset distribution and IL-2 receptor (IL-2 R) p55–p75 subunit expression in patients with cancer of different sites

The aim of the study was to evaluate the subset distribution and the IL-2 R p55–p75 subunit expression on unstimulated and phytohemagglutinin (PHA)-stimulated (at 3-d) peripheral blood mononuclear cells (PBMC), of patients with solid cancers of different sites. Indeed the expression of the two subunits of IL-2R is an essential prerequisite for The action of the IL-2 on CD8⁺, CD16⁺ lymphocytes as effectors in antitumor activity (LAK-cells). The subset distribution (CD3, CD4, CD8, CD16, DR) was assessed by cytofluorometry with specific monoclonal antibodies (MAbs); the p55 (CD25) and p75 subunit expression was evaluated by specific MAb (OKT26a and anti-p75). Ninety patients with advanced cancer (mainly non-small cell lung cancer [NSCLC], head and neck cancer, and gynecological cancer; mean age 55 yr; range 27–80) were studied. Thirty-five age- and sex-matched healthy subjects were studied as controls. Our data show that there is no significant difference in the subset distribution between cancer patients and controls. Furthermore, no difference has been found in the expression of p55 subunits on unstimulated PBMC between cancer patients and controls. No difference has been found in the expression of both p55 and p75 subunits on PHA-stimulated PBMC between cancer patients and controls. Our results can support the rationale for further clinical trials with IL-2 in solid malignancies.