Joint immobilization is commonly used for the treatment of joint injuries, but it causes articular cartilage degeneration. The purpose of this study was to clarify the reversibility of immobilization-induced articular cartilage degeneration using rat knee joints. Immobilization of rat knee joints induces atrophic changes in the non-contact area, loss of chondrocytes in the contact area, and hypertrophy of chondrocytes in the transitional area of the articular cartilage. The unilateral knee joints of adult male rats were rigidly immobilized at 150° of flexion with a plate and screws for 1, 2, and 4 weeks. After the experimental periods, the fixation devices were removed and the rats moved freely for 16 weeks. Sham-operated rats were used as a control. Sagittal sections at medial midcondylar regions of the knee were assessed with histological and histomorphometric methods. Mechanical properties were assessed by measuring the sound speed with scanning acoustic microscope. Reduction of cartilage proteoglycan in the non-contact area was almost reversible, but hypertrophy of chondrocytes in the transitional area and loss of chondrocytes in the contact area were irreversible even at 1-week immobilization-remobilization group. Sound speed of the articular cartilage in the contact area was not restored. These results indicate that atrophic changes through decreased mechanical stress in the non-contact area were reversible, but loss of chondrocytes and hypertrophy of chondrocytes in the contact and transitional areas through increased mechanical stress by rigid immobilization were irreversible after remobilization. Clinicians should be aware that even a short-term rigid immobilization could cause irreversible articular cartilage damage.
Pulmonary thromboembolism (PE) may occur upon a patient's first postoperative attempt of ambulation. PE is a serious complication, often leading to shock or sudden death. Reported rates of PE following gynecologic surgery are between 0.3% and 0.8%, while the incidence of postoperative deep-vein thrombosis (DVT), the major cause of PE, is between 17% and 20%. Therefore, effective preventive measures, such as preoperative assesment for asymptomatic DVT, should be considered. It is well known that DVT and/or PE are associated with large uterine fibroids, the common, benign tumor of myometrium. Here, to establish the statistical relationship between DVT risk and uterine fibroid size/weight, we assessed the preoperative DVT rate with respect to three possible risk factors: age, obesity level, and uterine size/weight. A total of 361 patients with uterine fibroids undergoing hysterectomy between July, 2003 and December, 2009 were enrolled. All patients were evaluated for preoperative DVT; the results were stratified for statistical comparison by patient age, BMI, and uterine weight. There was no statistical difference in the DVT rate for patients stratified by age (below age 45 years or older) or BMI (below 25 or higher). By contrast, the rate of DVT was significantly higher for patients with uterine weights of 1,000 gm or more (11.5% [7/61]) compared with weights below 1,000 gm (3.0% [9/300]). None of the patients studied developed PE. In conclusion, the incidence of DVT is significantly higher in cases where uterine weight is 1,000 gm or more (ie, adult head size on pelvic examination).
ST-segment elevation myocardial infarction (STEMI) is the most severe type of heart attack, and primary percutaneous coronary intervention (PCI) is the first line treatment for STEMI. However, these patients are at higher risk of contrast-induced nephropathy (CIN), which increases the length of hospital stay and mortality rate. Anisodamine, an alkaloid extracted from a Chinese herb, has been shown to exert protective effects on the renal function. The aim of this study was to investigate the protective effect of anisodamine on CIN in STEMI patients undergoing primary PCI. A total of 126 consecutive STEMI patients were randomly assigned to receive anisodamine (n = 60) or placebo (control, n = 66) from admission to 24 hours after PCI. The serum creatinine (SCr) concentrations, estimated glomerular filtration rate (eGFR) and incidence of CIN were measured on admission, and 24, 48 and 72 hours after PCI between the two groups. We found that the renal function of all patients after PCI underwent a course from injury to recovery. The incidence of CIN was 5.0%, 8.3%, and 6.7% at 24, 48 and 72 hours, respectively, after primary PCI in anisodamine group, while in control group it was 16.7%, 22.7%, and 19.7%, respectively. The incidence of CIN in anisodamine group was lower than that in control group during 72 hours after PCI (all P < 0.05). In conclusion, intravenous infusion of anisodamine before and after primary PCI may reduce the occurrence of CIN in STEMI patients undergoing primary PCI, without serious side effects.
Amplification of the human telomerase RNA component (hTERC) gene occurs early in cervical cancer development. Telomerase, the product of the hTERC gene, plays an important role in tumor cell apoptosis and genomic stability. Given the numerous similarities between esophageal and cervical cancers, we hypothesized that hTERC gene amplification may also be related with esophageal cancer development. We therefore examined 189 tissue sections from 63 cases of esophageal cancer and preneoplastic lesions. hTERC gene amplification in the lesions was detected by interphase fluorescence in situ hybridization. Of the 189 tissue sections, 149 were successfully evaluated (40 samples were excluded because of inappropriately preparation) and were classified as normal (n = 45), atypical hyperplasia I (n = 27), atypical hyperplasia II/III (n = 22), and squamous cell carcinomas (SCCs; the most common type of esophageal cancer) (n = 55). hTERC gene expression was not detected in normal esophageal tissue, whereas its expression was detected in atypical hyperplasias I (25.9%), atypical hyperplasia II/III (54.5%), and SCCs (90.9%) (p < 0.05). The average copy numbers of hTERC in atypical hyperplasias I and II/III, as well as SCCs were 2.19, 2.35, and 2.64, respectively. In particular, the numbers of abnormal nuclei in atypical hyperplasias II/III were significantly higher than those of in atypical hyperplasia I (p < 0.05). The hTERC gene amplification was not related with patient gender, histological stage, lymph nodes metastasis, and SCC differentiation grade (p > 0.05). All these findings suggest that hTERC gene amplification is associated with SCC development.
Osteoporosis is a common disorder in aging populations that imposes considerable health problems. Tartrate-resistant acid phosphatase type 5b (TRAP-5b) is derived from osteoclasts, and is involved in normal bone homeostasis. Recently, a novel assay system for TRAP-5b, the fragments absorbed immunocapture enzymatic assay method, has been developed. To evaluate the suitability of TRAP-5b as a screening marker for bone mineral density (BMD), we explored the correlations between serum TRAP-5b concentrations and laboratory findings, body mass index, or BMD in 462 community-dwelling elderly individuals (249 men and 213 women, age 73.4 ± 6.5 years) who participated in a regular medical screening program. By multivariate linear regression analysis adjusted for confounding factors, TRAP-5b was significantly correlated with body mass index (β = −0.005, p = 0.043), alkaline phosphatase, a marker for osteoid formation and calcification (β = 0.001, p < 0.001), and triglyceride (β = −0.097, p = 0.016) in men, and with body mass index (β = −0.009, p = 0.025), alkaline phosphatase (β = 0.001, p < 0.001), calcium (β = −0.059, p = 0.039), and bone trabecular area ratio (β = −0.47, p = 0.025) in women. In conclusion, the elevated serum level of TRAP-5b is independently correlated with the decreased BMD in women, but not in men. Because measurement of TRAP-5b is not affected by food intake, and blood samples can be collected at any time of the day, we suggest the suitability of serum TRAP-5b as a simple marker for the evaluation of BMD in women.
Fertilization promoting peptid (FPP) is essential for capacitation and acrosome reaction. The mouse t-complex protein 11 (Tcp11) gene, which encodes the receptor of FPP, plays an important role in fertilization. We had identified three alternative splicing products of its human homologous gene, TCP11, nominated as TCP11a, TCP11b and TCP11c. Their testis-specific expression had been noted, suggesting that TCP11 may play an important role in spermatogenesis and sperm function. In order to explore the function of TCP11, we investigated its expression, subcellular location and binding protein in the sperm. RT-PCR assay shows that all isoforms of TCP11 are present in both human testis and sperm. However, we could only detect the expression of 56-kDa protein, representing TCP11a and TCP11c, but not TCP11b, by western blot analysis. Furthermore, the expression level of 56-kDa TCP11 protein was lower by about threefold in sperm samples containing over 15% of coiled sperms than the level in sperm samples with normal morphology. The coiled sperm, which shows a coiling or bending back of the tail on itself, is associated with infertility. In addition, several TCP11a-binding proteins were isolated using full-length TCP11a as bait. Among them, we focused on outer dense fiber 1 (ODF1), a component of sperm tail outer dense fibers, because outer dense fibers contribute to the distinct morphology and the function of sperm tail. Co-immunoprecipitation assays of sperm cell extracts confirmed that TCP11 protein interacted with ODF1. These results suggest that TCP11 may be responsible for the sperm tail morphology and motility.
Lymphotoxin-alpha (LTA), a pro-inflammatory cytokine, has been implicated in the pathogenesis of coronary atherosclerosis. Meanwhile, association of some single nucleotide polymorphisms (SNPs) of LTA gene with coronary artery disease (CAD) has been evaluated; however, the results are irreproducible. We therefore investigated the relationship between four SNPs of LTA gene and CAD in Han Chinese: G+10A (rs1800683, 5'-untranslated region), A+80C (rs2239704, 5'-untranslated region), T+496C (Cys13Arg, rs2229094, exon 2), and C+804A (Thr26Asn, rs1041981, exon 3). Genotyping was performed in 438 CAD patients and 330 healthy controls. Single-locus analysis showed that the genotype and allele frequencies of G+10A polymorphism exhibited marginal differences between CAD patients and controls, although no statistical significance was observed after the Bonferroni correction. Logistic regression analysis revealed that GG genotype of G+10A polymorphism was significantly associated with the risk of CAD under the dominant mode, whereas no significant association was detected between A+80C polymorphism and CAD. In contrast, individuals carrying TT or TC genotype of T+496C polymorphism showed a decreased CAD risk relative to those with CC genotype under the recessive mode. Likewise, CC genotype of C+804A polymorphism was associated with a protective effect on CAD under the dominant mode. Further, in haplotype analysis, the haplotype G-C-T-C (in order of rs1800683, rs2239704, rs2229094 and rs1041981) was significantly associated with a decreased risk of CAD after assigning the most common haplotype A-C-T-A as a reference. In conclusion, we show a protective effect of the haplotype G-C-T-C on the occurrence of CAD, suggesting the involvement of LTA in CAD pathogenesis.
Sleep problems are known to be risk factors for subsequent emotional and behavioral difficulties in childhood and adolescence. To date, there has been no study investigating the relationships between sleep habits and behavioral problems in a large nonclinical sample of preschool age children. The aim of this study was to examine these relationships and factors associated with the sleep habits of preschool age (2 to 5 year old) children. Their mothers (n = 1,746) completed a multiple-choice questionnaire about the sleep habits and behavior problems of their children, as well as their own sleep habits and working hours at Tokyo metropolitan public nursery schools. The short sleep duration group showed significantly higher aggressive scores than the long sleep duration group among 2- to 3-year-old children, and the irregular bedtime group showed significantly higher aggressive and attention problem scores than the regular bedtime group among 4- to 5-year-old children. Univariate and multivariate logistic regression analyses revealed that children's late bedtime was associated with their mother's late waking-up time, and late schedule of both the mother's leaving and returning home. This study recognized an association between behavioral problems and poor sleep habits among preschool-age children. It is important for children to sleep regularly and adequately in order to decrease their behavior problems. In conclusion, appropriate management of children's sleep by their mothers is necessary for promoting sleep-related health of children.
Seasonal variations in blood pressures should be kept in mind when controlling blood pressure in hypertensive patients. Seasonal variations in glomerular filtration rate (GFR) also may have a clinical significance. However, it is time-consuming to measure GFR directly. We therefore examined the seasonal variation in estimated glomerular filtration rate (eGFR) based on serum creatinine levels in hypertensive patients without CKD (eGFR ≥ 60 mL/min/1.73 m2) and those with chronic kidney disease (CKD) (eGFR < 60 mL/min/1.73 m2). This study included 47 hypertensive patients without CKD (69 ± 11 yrs) and 55 hypertensive patients with CKD (76 ± 8 yrs). The eGFR was determined from the equation: eGFR = 194 × age−0.287 × (serum creatinine)−1.094 (× 0.739 if female). Overall, both groups of hypertensive patients demonstrated similar seasonal variations in eGFR. Importantly, hypertensive patients without CKD and those with CKD showed the lower eGFR in summer (June-August) (71.8 ± 13.2 and 37.2 ± 13.0 mL/min/1.73 m2, respectively) compared with the eGFR in spring (March-May) (77.9 ± 13.0 and 43.0 ± 14.0 mL/min/1.73 m2, respectively) (p < 0.05). The decrease in eGFR from spring to summer was similar for both types of hypertensive patients (without CKD, −6.1 ± 7.0; with CKD, −5.8 ± 5.2 mL/min/1.73 m2). However, the percent change in eGFR from spring to summer was greater in hypertensive patients with CKD (−13.8 ± 9.4 %) than in those without CKD (−7.7 ± 8.3 %) (p = 0.001). In conclusion, careful observation regarding renal function is needed for hypertensive patients with CKD during summer.
Necrotizing enterocolitis (NEC) is the most common neonatal gastrointestinal emergency, predominantly affecting low-birth weight, premature infants. Early clinical signs of NEC are nonspecific and the laboratory findings are not fully reliable. Its severe morbidities and rapid progression require the application of new biomarkers for early diagnosis and intervention. The complement activation product, C5a (anaphylatoxin) has been reported to be a contributing factor leading to mesenteric ischemia/reperfusion injury which is a predisposing factor in the pathogenesis of NEC. Therefore, our aim was to evaluate the efficacy of serial C5a measurements in the diagnosis and follow-up of NEC. Preterm infants, whose gestational age and weight matched each other, were grouped as controls (n = 23) and NEC (n = 22). Serum levels of C5a, serum amyloid-A (SAA), C-reactive protein (CRP), and interleukin-6 (IL-6) levels were measured on the third day of life for the control group and on the day of diagnosis (1st day), 3rd and 7th days of the NEC group. C5a, SSA, CRP, and IL-6 levels were significantly higher in the NEC patients compared to the control group (P < 0.05) in the follow-up. Additionally, serum levels of C5a were found to be more accurate than the other parameters for the prediction of death and requirement for surgery at the time of diagnosis (P < 0.05). In conclusion, C5a may be useful as a new marker for both diagnosis and follow-up of infants with NEC in combination with clinical and radiographical findings.
The Miyagi Study is an epidemiological study of malignant lymphoma, including immunological and genetic analyses, constructed by a population-based registration system covering Miyagi prefecture, Japan. A total of 1,552 newly diagnosed cases in Miyagi between 2002 and 2008 were enrolled in this study; 75% were B-cell lymphomas, 19% were T-cell and natural killer-cell (T/NK-cell) lymphomas, and 5% were Hodgkin's lymphomas. The most frequent subtype of B-cell lymphoma is diffuse large B-cell lymphoma, followed by follicular lymphoma and extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (51%, 24% and 8%, respectively). Thus, follicular lymphoma accounts for 18.2% of newly diagnosed cases in Miyagi; unexpectedly, its frequency is similar to that reported in Western countries. The common subtypes of T/NK-cell lymphoma are peripheral T-cell lymphoma, angioimmunoblastic T-cell lymphoma, and adult T-cell leukemia/lymphoma (30%, 15% and 14%, respectively). Most of the data are similar to those reported in Asian countries, except for follicular lymphoma. We also analyzed the CD20 expression in B-cell lymphomas by flow cytometry for the cell membrane expression and by immunohistochemistry for the cytoplasmic expression. The cell membrane expression of CD20 protein may determine the susceptibility of B-cell lymphomas to anti-CD20 antibody therapy. The lack of CD20 expression was confirmed by both methods in 4 cases of 585 newly diagnosed cases (0.7%) and in 5 of 67 recurrent cases (7.5%). Furthermore, 23 cases (6.5%) showed the discrepancy of CD20 expression between both methods. The Miyagi Study has revealed the latest epidemiological features of malignant lymphoma in Japan.