Multifactorial Comparative Analysis of Platelet-Rich Plasma and Serum Prepared Using a Commercially Available Centrifugation Kit.

Background Platelet-rich plasma (PRP) is an autologous product prepared by centrifuging whole blood. PRP is reported to have high tissue repair potential and anti-inflammatory properties. Recently, PRP has become a potential treatment option for osteoarthritis, contributing to pain relief and locomotive improvement. However, the underlying therapeutic mechanisms and key biochemical factors in PRP remain unclear. This study aimed to estimate the major factors for tissue repair involved in PRP treatment by comparing between serum and PRP prepared from the same patients using the Luminex assay. Methodology Blood samples were collected from nine healthy volunteers, and serum and PRP were prepared. PRP was prepared using a PEAK©ï¸Ž PRP SYSTEM kit of DePuy Synthes Mitek Sports Medicine (Raynham, Massachusetts, USA), which is a commercially available PRP preparation kit. The white blood cell count, hemoglobin level, and platelet count were automatically measured for both whole blood and PRP in the hospital's clinical laboratory using the XE-5000™ Automated Hematology System (Sysmex, Kobe, Japan). Comparative analysis of biological factors was then performed using the Luminex assay on serum and PRP. Results PRP was found to have significantly higher white blood cell and platelet counts and lower hemoglobin levels than whole blood. Furthermore, PRP contained significantly higher levels of various factors, including interleukin (IL)-1ra, IL-10, IL-13, C-C motif chemokine ligand (CCL)-2, CCL3, CCL4, CCL8, CCL13, CCL21, C-X-C motif chemokine ligand (CXCL)-10, matrix metalloproteinase (MMP)-3, MMP-9, cluster of differentiation (CD) 40 ligand, vascular endothelial growth factor (VEGF), VEGF-C, platelet-derived growth factor (PDGF)-AB, PDGF-BB, and bone morphogenic protein (BMP)-2. Additionally, IL-1ra and IL-4 showed significant correlations with white blood cell counts in PRP, whereas VEGF had a significant correlation with platelet counts. Conclusions PRP contains various factors in higher quantities than serum. Specifically, the notable increase in the anti-inflammatory cytokine IL-1ra is suggested to play a key role as a major therapeutic mechanism of PRP.

The thymus and activation-regulated chemokine (TARC) level in serum at an early stage of a drug eruption is a prognostic biomarker of severity of systemic inflammation.

BACKGROUND: In severe drug eruptions, precise evaluation of disease severity at an early stage is needed to start appropriate treatment. It is not always easy to diagnose these conditions at their early stage. In addition, there are no reported prognostic biomarkers of disease severity in drug eruptions. The aim of this study was to test whether the thymus and activation-regulated chemokine (TARC) level in serum at an early stage of a drug eruption can serve as a prognostic biomarker of systemic inflammation. METHODS: Study participants included 76 patients who received a diagnosis of a drug eruption, one of the following: drug rash with eosinophilia and systemic symptoms/drug-induced hypersensitivity syndrome, maculopapular exanthema, and erythema multiforme. Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) was eliminated in this study because scoring system for evaluating the severity was established. Correlation coefficients between serum TARC levels and indicators of systemic inflammation, including the neutrophil-to-lymphocyte ratio, Glasgow prognostic score, modified systemic inflammatory response syndrome (mSIRS) score, and C-reactive protein in serum were evaluated. RESULTS: Serum TARC levels positively correlated with the neutrophil-to-lymphocyte ratio, Glasgow prognostic score, mSIRS score, C-reactive protein, albumin, white blood cell count, body temperature, and pulse rate. TARC levels negatively correlated with systolic blood pressure. Among these parameters, the mSIRS score showed strong correlation (correlation coefficient: 0.68). CONCLUSIONS: Serum TARC levels correlate well with indicators of systemic inflammation and of disease severity among patients with a drug eruption except SJS/TEN. Serum TARC may be a prognostic biomarker of severity of inflammation in drug eruptions.

Serum TARC levels are strongly correlated with blood eosinophil count in patients with drug eruptions.

BACKGROUND: This study aims to evaluate the relationship between serum thymus and activation-regulated chemokine (TARC) levels with various clinicopathological conditions in patients with drug eruptions. The value of TARC in diagnosing drug-induced hypersensitivity syndrome (DIHS) was also examined. METHODS: Study participants included 84 patients who presented with generalized eruptions suspected to be drug-related, including DIHS, Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN), maculopapular exanthema (MPE), erythema multiforme (EM), erythroderma, and toxicoderma. The correlation coefficients between serum TARC levels and clinical parameters in peripheral blood samples were calculated. RESULTS: Serum TARC levels in patients with DIHS were higher than those found in patients with SJS/TEN, MPE, EM, and toxicoderma. TARC levels had 100% sensitivity and 92.3% specificity in diagnosing DIHS, with a threshold value of 13,900 pg/mL. Serum TARC levels positively correlated with age, white blood cell (WBC) count, neutrophil count, eosinophil count, monocyte count, atypical lymphocyte (Aty-ly) count, serum blood urea nitrogen (BUN) levels, and creatinine (Cr) levels. It negatively correlated with serum total protein (TP), albumin (Alb), and estimated glomerular filtration rate (eGFR). Among these clinical parameters, blood eosinophil counts were most strongly correlated with serum TARC levels, with a correlation coefficient of 0.53. CONCLUSIONS: Serum TARC levels are well correlated with blood eosinophil counts in patients with generalized drug eruptions, indicating that Th2-type immune reactions underlie TARC production. Serum TARC measurements also have potent diagnostic value for DIHS, with high sensitivity and specificity.

The impact of tics, obsessive-compulsive symptoms, and impulsivity on global functioning in Tourette syndrome.

This study investigated the relationships between tics, obsessive-compulsive symptoms (OCS), and impulsivity, and their effects on global functioning in Japanese patients with Tourette syndrome (TS), using the dimensional approach for OCS. Fifty-three TS patients were assessed using the Yale Global Tic Severity Scale, the Dimensional Yale-Brown Obsessive-Compulsive Scale, the Impulsivity Rating Scale, and the Global Assessment of Functioning Scale. Although tic severity scores were significantly and positively correlated with OCS severity scores, impulsivity severity scores were not significantly correlated with either. The global functioning score was significantly and negatively correlated with tic and OCS severity scores. Of the 6 dimensional OCS scores, only aggression scores had a significant negative correlation with global functioning scores. A stepwise multiple regression analysis showed that only OCS severity scores were significantly associated with global functioning scores. Despite a moderate correlation between tic severity and OCS severity, the impact of OCS on global functioning was greater than that of tics. Of the OCS dimensions, only aggression had a significant impact on global functioning. Our findings suggest that it is important to examine OCS using a dimensional approach when analyzing global functioning in TS patients.

Obsessive-compulsive symptom dimensions in Japanese tourette syndrome subjects.

OBJECTIVES: To investigate the current and lifetime frequency and severity of obsessive-compulsive (OC) symptom dimensions in Tourette syndrome (TS) patients, and how these dimensions affect clinical characteristics. METHODS: Forty TS outpatients (29 males, 11 females) were interviewed with the Dimensional Yale-Brown Obsessive-Compulsive Scale (DY-BOCS), the Yale Global Tic Severity Scale (YGTSS), the Shapiro Tourette Syndrome Severity Scale, and the Global Assessment of Functioning (GAF). RESULTS: OC symptoms were present in 80% of the total sample. The miscellaneous and the symmetry dimensions were the most frequent at the "current" and "lifetime" surveys, respectively. The aggression dimension had the smallest difference between "worst ever" and current ratings among the all OC symptom dimensions. TS patients with the aggression dimension (n=7) had significantly lower scores in the GAF scale and higher frequencies of coprolalia. There were significant correlations between the YGTSS severity scores and specific DY-BOCS dimensions. CONCLUSION: OC symptoms are frequent in TS subjects and there were differences in the frequency, severity, and course of the OC symptom dimensions. These results emphasize the need for future longitudinal studies using a dimensional approach for the evaluation of OC symptoms in tic disorders.

Association between Tourette syndrome and comorbidities in Japan.

The purpose of this study was (1) to document cases of Tourette syndrome (TS) with comorbidities such as obsessive-compulsive symptoms (OCS) and hyperkinetic disorder (HD), and (2) to examine differences in clinical characteristics between TS patients with OCS and HD and those without these comorbidities. The subjects in the study were 88 Japanese TS patients (67 males and 21 females; mean age: 15.2years) who were treated by 31 clinicians including psychiatrists and pediatricians. Data on tic symptoms, comorbidities and severity were scrutinized. OCS were present in 42.0% of the subjects, while HD accounted for 28.4%. In the TS+OCS and/or HD group, coprophenomana, impulsiveness/aggression, school refusal, self-injurious behaviors (SIB), and clumsiness were significantly more frequent than in the TS-only group. Also, tic symptoms and impairment during the worst period was significantly severer in the TS+OCS and/or HD than in the TS-only group. When the age-matched TS+all OCS group (i.e., the young TS+OCS and TS+OCS+HD group) was compared with the TS-only group, it was found that the rates of impulsiveness/aggression, school refusal and SIB were significantly higher and the degree of global severity was significantly more intense in the young TS+all OCS group than in the TS-only group. The impact to clinical characteristics of TS from OCS was suggested to be slightly greater than that from HD. There was little ethnic difference in TS pathogenesis in terms of the impact of comorbidities. Further investigation is required to gain deeper insights into the relationships between TS, OCD or OCS and HD.

Rage attacks and aggressive symptoms in Japanese adolescents with tourette syndrome.

OBJECTIVE: This study was conducted to explore possible causes of rage attacks as well as clinically significant aggressive symptoms in Japanese adolescents with Tourette syndrome (TS). METHODS: The subjects included 29 adolescents (23 males, 6 females; mean age: 13.5+/-3.7 years). Eighteen subjects (62.1%) were diagnosed with TS only, 11 (37.9%) with TS and comorbidities, including attention-deficit/hyperactivity disorder and obsessive-compulsive disorder. Parents completed the Child Behavior Checklist. Clinically significant aggressive symptoms were assessed using two pilot tools, the Rage Screen and Questionnaire and the Clinical Rating of Aggression. RESULTS: Thirteen subjects (44.8%) were judged to have clinically significant aggressive symptoms, according to the Clinical Rating of Aggression. Twelve met criteria for recurrent rage attacks, according to the Rage Screen and Questionnaire. Between the 13 aggressive and 16 non-aggressive subjects, no significant differences were found in age, gender, psychiatric comorbidities, or concurrent medication. Child Behavior Checklist ratings to compare 11 aggressive and 12 non-aggressive subjects <16 years of age revealed elevated t-test scores on the anxious/depressed, thought problems, aggressive, internalizing, externalizing subscales, and total scale in the aggressive group versus the non-aggressive group. CONCLUSION: Rage attacks and clinically significant aggressive symptoms are common problems in Japanese TS youth. Psychiatric morbidity appears associated with impulsive-aggressive symptoms. Treatment implications from these findings need to be explored further.

Molecular characterization of Japanese sillago vitellogenin and changes in its expression levels on exposure to 17beta-estradiol and 4-tert-octylphenol.

We cloned a full-length cDNA encoding vitellogenin (VTG) from a marine teleost, the Japanese sillago Sillago japonica. The cloned sillago VTG contained signal peptide, lipovitellin heavy chain, phosvitin, lipovitellin light chain, and beta'-component in the order from the N-terminus. An exposure to 17beta-estradiol significantly increased the levels of plasma VTG, but not hepatic VTG mRNA in males. Neither plasma VTG nor hepatic VTG mRNA levels were affected by the exposure to 4-tert-octylphenol. Hepatic VTG mRNA levels in males increased at 1 day after intraperitoneal administration of 17beta-estradiol but decreased in the subsequent 5 days. However, plasma VTG levels remained high for 5 days after administration, suggesting that the accumulation period of plasma VTG is longer than that of hepatic VTG mRNA in males. Therefore, VTG mRNA may be a suitable indicator of temporal exposure to estrogenic chemicals in the environment, whereas plasma VTG is useful to detect consecutive exposure.

Catatonia in individuals with autism spectrum disorders in adolescence and early adulthood: a long-term prospective study.

The objective is to cast light on diagnosis and catastasis, course, and comorbidity as concerned with catatonia in patients with autism spectrum disorders (ASDs) with respect to long-term prospective follow-up. Eleven patients (all male) were enrolled. The mean age and the mean follow-up duration were 27.6 years (standard deviation (SD) 5.5) and 18.7 years (SD 8.7), respectively. The mean IQ was 27 (SD 16.4). Information was garnered from medical case records; current examination and observation of patients, interview of parents, and questionnaires completed by parents or other caretakers. Informed consent was obtained from the parents. Criteria for catatonia in this study were: (1) abrupt stop of movements and maintenance of immobility or bizarre posture beginning in adolescence and early adult life, (2) such a cataleptic state had continued for at least several minutes and appeared many times a day to the point of interfering with daily activities. We described two typical catatonic cases of ASDs. The average onset age was 19 years (SD 6). In all cases, our diagnostic criteria of catatonia evaluating at worse are fully compatible with those of Diagnostic and Statistical Manual of Mental Disorders, 4th ed. (DSM-VI). In 8 out of 11, the onset of catatonia was clearly preceded by the appearance of slowness in movements accompanying the exacerbation of obsessive-compulsive symptoms. Catatonia was also found to have some connection with Tourette syndrome (3 cases), adjustment disorders (N=1), and depressive mood disorders (N=1). In one case, the manifestations of catatonia had to be distinguished from parkinsonism caused by antipsychotics. Catatonia in ASDs seems to be a chronic condition in most cases. However, there were also a few cases in which catatonia repeatedly aggravated over short spans of time. Catatonia in ASDs may be considered an epiphenomenon of ASDs or a manifestation of comorbidity in adolescence or early adulthood.

Obsessive-compulsive symptoms in parents of Tourette syndrome probands and autism spectrum disorder probands.

Obsessive-compulsive symptoms (OCS) frequently occur in patients with Tourette syndrome (TS) and autism spectrum disorders (ASD). It has been suggested that genetic factors play a role in the transmission of both TS and ASD and that obsessive-compulsive disorder (OCD) may have some genetic relationship with these disorders. The objective of this study was to explore whether the OCS associated with TS and ASD were found in the parents of TS and ASD probands by comparing them with normal controls. The subjects were parents of 13 TS and 16 ASD probands. All parents underwent an examination for tic symptoms and OCD, and completed the Maudsley Obsessional Compulsive Inventory (MOCI) and State-Trait Anxiety Inventory (STAI). No significant differences were observed in the MOCI and STAI scores among all three groups. However, the MOCI total score was higher in fathers of ASD probands than in male normal controls with a marginal significance. There was a significant tendency for the mean cleaning score of MOCI in fathers of ASD probands to be higher than that in male normal controls, and the mean checking score in fathers of ASD probands was fourfold higher than that in male normal controls, although there was no significant difference. No significant relationship was observed between OCS in TS or ASD probands and OCS of their parents. Further studies on OCD and OCS including a dimensional approach within ASD families are needed.

Clinical characteristics of adult patients with tics and/or Tourette's syndrome.

OBJECTIVE: This study was conducted to describe the natural course of tic disorders over a long period of time in Japanese adults patients with Tourette's syndrome (TS) in terms of symptomatology. METHODS: An extensive literature on TS cases was reviewed selectively and 31 TS patients (mean age: 31.4 years; sex: 28 males and 3 females) at our outpatient clinic were examined. The mean follow-up period of the patients was 7.6 years (SD: 8.1; 0 to 26). All the data available for this study, including medical charts, were examined systematically by two experienced child psychiatrists. RESULTS: The adult patients with tic disorders could be classified into the four groups: group A - tics only, group B - tics + comorbidities, group C - comorbidities only and group D - sub-clinical (remission) cases. Our 31 subjects consisted of 10 patients (32.3%) for group A, 14 (45.2%) for group B, 7 (22.6%) for group C, and 0 for group D. CONCLUSIONS: Further investigation into the natural course and clinical characteristics of adult TS needs to be done in order to acquire a better understanding of the broad spectrum of TS and to make improvements to the treatment for this illness.

Type III intestinal metaplasia and carcinoma express an identical carbohydrate-epitope revealed by a novel monoclonal antibody (2D11).

A monoclonal antibody (2D11, IgG2b) obtained by immunizing mice with a mucin fraction of the human gastric mucosa reacted specifically to intestinal metaplasia of human gastric mucosa and fetal intestinal mucosa but not to normal adult gastric, small intestinal or colonic mucosa in immunohistochemical staining. The results of Western blotting indicated that 2D11 recognized the high molecular weight glycoprotein(s) (mucin) of the stomach. Treatment of the antigens with sodium periodate abolished their reactivity to 2D11, and digestion of the antigens with beta-galactosidase reduced their reactivity to 2D11. Digestion of the antigens with pronase had no effect, however, suggesting that 2D11 recognizes the oligosugar moiety but not the peptide moiety of the antigens. Further immunohistochemical investigation showed that the reactivity of 2D11 was restricted to the Type IotaIotaIota intestinal metaplasia that is identified by a characteristic staining pattern with the high iron diamine-Alcian blue stain. 2D11 also reacted in high frequency to adenocarcinomas of the stomach (66.7%), pancreas (66.7%) and gallbladder (50.0%), but in low frequency to those in lung (8.3%) and colon (11.1%). It is of interest that 2D11 reacted to very restricted regions of the gastric adenocarcinomas. All monoclonal antibodies to mucin polypeptides (MUC1, 2, 3, 5AC and 6) examined stained intestinal metaplasia and carcinomas in a different pattern from 2D11 in immunohistochemistry. These facts indicate that Type IotaIotaIota intestinal metaplasia and carcinomas express carbohydrate chains identical to those expressed in the fetal intestinal mucosa, suggesting that both of them are closely related to fetal intestinal mucosa.