Correlations between both the expression levels of inflammatory mediators and growth factor in medial perimeniscal synovial tissue and the severity of medial knee osteoarthritis

An enhanced expression of the inflammatory mediators in the perimeniscal synovium in knee osteoarthritis (OA) has been suggested to contribute to progressive cartilage degeneration. However, whether the expression levels of these molecules correlated with the severity of OA still remained unclear. Medial perimeniscal synovial samples were obtained from 23 patients with Kellgren-Lawrence (K/L) grades 2 to 4 of medial knee OA. Immunohistochemical analysis of the synovium revealed that the MMP-1, COX-2 and IL-1β expression of the patients with K/L 4 to be significantly reduced in comparison to those with either K/L 2 or 3, while the TGF-β expression showed the opposite. The synovial expression of MMP-1 and IL-1β showed a significant negative correlation with the severity of OA, while that of TGF-β again showed the opposite. In conclusion, although synovial inflammation remained active, the MMP-1, COX-2 and IL-1β expression in synovium decreased depending upon the severity of OA, while the TGF-β expression increased.     

Gastrointestinal stromal tumors of the small intestine in pediatric populations: a case report and literature review

An 18-year-old girl presented with abdominal pain and a tumor was subsequently detected in the jejunum. We therefore carried out a wedge resection of the jejunum. The diagnosis of GIST was confirmed histologically, and a mutation in exon 9 of the c-kit gene was observed. GISTs are rare in pediatric populations and pediatric GISTs occur predominantly in females and are characterized by a multifocal gastric location and a wild-type phenotype for the c-kit genes. The features of pediatric GISTs of the small intestine have not yet been categorized, and to date, only 11 cases in patients younger than 18 years have been reported. These cases did not occur primarily in females and tended to present as single tumors with mutations in the c-kit gene. This suggests that these cases do not have the same features as pediatric gastric GISTs, but instead are similar to adult GISTs. In pediatric populations, GISTs of the small intestine were expected to show a better response to imatinib treatment than gastric GISTs because of the alterations in the c-kit gene.     

Establishment of Long‐Term Model throughout Regular Menstrual Cycles in Immunodeficient Mice

Citation Kikuchi‐Arai M, Murakami T, Utsunomiya H, Akahira J, Suzuki‐Kakisaka H, Terada Y, Tachibana M, Hayasaka S, Ugajin T, Yaegashi N. Establishment of long‐term model throughout regular menstrual cycles in immunodeficient mice. Am J Reprod Immunol 2010 Problem The number of uterus natural killer (NK) cells change through the menstrual cycle, but the origin of uterus NK cell was not unclear. Our aims are to study whether we can reproduce repetition of menstrual cycle and to reveal the origin of uterus NK cells. Method of study Endometrial samples were obtained from fertile women, and the tissues were transplanted into ovariectomized non‐obese diabetic (NOD)/severe combined immunodeficiency (SCID)/γCnull (NOG) mice. Mice were treated with sex hormones which were in accord with human menstrual cycle. Results The replants showed similar histological changes as in eutopic endometrium repeatedly. CD56‐positive, CD16‐negative NK cells increased significantly during the treatment with estradiol and progesterone combination. Conclusion Histological assessment demonstrated that this model of NOG mice repeatedly exhibited regular menstrual cycles, and this model mimicked not ‘ectopic endometrium’, but ‘eutopic endometrium’ in humans. Change in number of NK cells suggested that NK cell might be derived from the endometrium.     

Cancer cachexia—pathophysiology and management

About half of all cancer patients show a syndrome of cachexia, characterized by anorexia and loss of adipose tissue and skeletal muscle mass. Cachexia can have a profound impact on quality of life, symptom burden, and a patient’s sense of dignity. It is a very serious complication, as weight loss during cancer treatment is associated with more chemotherapy-related side effects, fewer completed cycles of chemotherapy, and decreased survival rates. Numerous cytokines have been postulated to play a role in the etiology of cancer cachexia. Cytokines can elicit effects that mimic leptin signaling and suppress orexigenic ghrelin and neuropeptide Y (NPY) signaling, inducing sustained anorexia and cachexia not accompanied by the usual compensatory response. Furthermore, cytokines have been implicated in the induction of cancer-related muscle wasting. Cytokine-induced skeletal muscle wasting is probably a multifactorial process, which involves a protein synthesis inhibition, an increase in protein degradation, or a combination of both. The best treatment of the cachectic syndrome is a multifactorial approach. Many drugs including appetite stimulants, thalidomide, cytokine inhibitors, steroids, nonsteroidal anti-inflammatory drugs, branched-chain amino acids, eicosapentaenoic acid, and antiserotoninergic drugs have been proposed and used in clinical trials, while others are still under investigation using experimental animals. There is a growing awareness of the positive impact of supportive care measures and development of promising novel pharmaceutical agents for cachexia. While there has been great progress in understanding the underlying biological mechanisms of cachexia, health care providers must also recognize the psychosocial and biomedical impact cachexia can have.     

Re-evaluation of detectability of liver metastases by contrast-enhanced CT: added value of hepatic arterial phase imaging

Purpose

We compared the detectability of liver metastases on 2- and 3-phase images using robust statistical methods. Nine radiologists evaluated unenhanced CT plus portal venous phase (2-phase) images and 2-phase plus hepatic arterial phase (HAP) (3-phase) images.

Materials and methods

Our study included 54 patients with primary malignant tumors who underwent 3-phase hepatic dynamic CT more than twice to screen for liver metastases; 24 had 1–6 liver metastases measuring 4–27 mm in diameter (median 13 mm). The other 30 had no metastases. Nine board-certified radiologists participated in our observer performance study. They specified the location of the metastatic lesions and rated the probability of metastatic nodules on 2-phase images acquired with and without HAP imaging. We used jackknife alternative free-response receiver operating characteristic (JAFROC) analysis to compare their performances.

Results

For all radiologists the area under the curve without and with HAP imaging was 0.86 and 0.88, respectively; the difference was significant (p = 0.04). For metastases smaller than 10 mm the averaged lesion localization fraction without and with HAP imaging was 0.17 and 0.26 (p < 0.01).

Conclusion

Adding HAP to 2-phase imaging improved the detectability of liver metastases, especially of lesions smaller than 10 mm.     

Ecology of hantaviruses in Mexico: Genetic identification of rodent host species and spillover infection

In our recent epidemiological survey conducted in Mexico for hantavirus infection, we identified three distinct viruses circulating in Mexican wild rodents, namely Montano virus (MTNV), Huitzilac virus (HUIV), and Carrizal virus (CARV). To gain a detailed understanding of hantavirus epidemiology and its associated hosts, 410 rodents were captured at eight collecting points in Morelos and Guerrero, Mexico, and examined for hantavirus seroprevalence, the presence of viral RNA, and rodent host species identification using cytochrome b gene sequences. Of the 32 species captured, seven species were positive for hantavirus: Peromyscus beatae (31/127; 24.4%), Reithrodontomys sumichrasti (6/15; 40%), Reithrodontomys megalotis (2/25; 8%), Peromyscus aztecus evides (1/1; 100%), Peromyscus megalops (1/41; 2.4%), Megadontomys thomasi (1/9; 11.1%), and Neotoma picta (1/6; 16.7%), with an overall prevalence of 10.5%; virus genome persisted in the majority of seropositive rodents. Nucleotide sequence and phylogenetic analysis showed that the viruses belonged mainly to the three lineages previously identified. The data showed that MTNV and CARV were primarily carried by P. beatae and R. sumichrasti, respectively. In addition, the data revealed an apparent complex interaction between hantaviruses and their hosts, suggesting active transmission and/or spillover infections within sympatric rodent species.     

Assessment of the otolith-ocular reflex using ocular vestibular evoked myogenic potentials in patients with episodic lateral tilt sensation

The otolith-ocular reflex in patients with episodic lateral tilt sensation without any other vestibular symptoms was assessed using ocular vestibular evoked myogenic potentials (oVEMP). Ten patients (6 men and 4 women, mean age=53.5) were enrolled. All patients had episodic lateral tilt sensation. Patients with a medical history of rotatory vertigo, loss of consciousness, head trauma, or symptoms or signs of central nervous dysfunction or proprioceptive dysfunction and those who had been definitely diagnosed with a disease that causes disequilibrium were excluded. All of the 10 patients had oVEMP tests and cervical VEMP (cVEMP) tests and underwent caloric tests. Eight of the 10 patients showed unilateral absence of oVEMP, one displayed a bilateral absence, and one displayed normal oVEMP. Concerning cVEMP, 4 patients showed a unilateral absence of cVEMP, one displayed unilaterally decreased responses and 5 displayed normal cVEMP. All patients showed normal bilateral caloric responses. The present study showed that patients with episodic lateral tilt sensation displayed abnormal otolith-ocular reflexes, as shown by their oVEMP, suggesting that these patients were suffering from utricular dysfunction.     

Infectious mononucleosis with atypical manifestations accompanied by transient IgM antibody response for cytomegalovirus

Infectious mononucleosis (IM) is a clinical syndrome caused by primary infection with Epstein–Barr virus (EBV) that is common in adolescents. In adults, particularly in elderly people, the clinical picture of IM tends to be atypical, often leading to a diagnostic challenge. Diagnosis is also complicated because infection with EBV can induce the synthesis of cross-reacting immunoglobulin M antibodies for other herpesviruses. We report an unusual case of infectious mononucleosis in a 34-year-old immunocompetent adult. Epidemiological studies indicate that the average age of primary EBV infection in developed countries is increasing. IM with atypical presentation will be a diagnostic challenge in the future as the number of EBV-naïve adults increases.     

Identification and characterization of an oocyte factor required for development of porcine nuclear transfer embryos

Nuclear reprogramming of differentiated cells can be induced by oocyte factors. Despite numerous attempts, these factors and mechanisms responsible for successful reprogramming remain elusive. Here, we identify one such factor, necessary for the development of nuclear transfer embryos, using porcine oocyte extracts in which some reprogramming events are recapitulated. After incubating somatic nuclei in oocyte extracts from the metaphase II stage, the oocyte proteins that were specifically and abundantly incorporated into the nuclei were identified by mass spectrometry. Among 25 identified proteins, we especially focused on a multifunctional protein, DJ-1. DJ-1 is present at a high concentration in oocytes from the germinal vesicle stage until embryos at the four-cell stage. Inhibition of DJ-1 function compromises the development of nuclear transfer embryos but not that of fertilized embryos. Microarray analysis of nuclear transfer embryos in which DJ-1 function is inhibited shows perturbed expression of P53 pathway components. In addition, embryonic arrest of nuclear transfer embryos injected with anti-DJ-1 antibody is rescued by P53 inhibition. We conclude that DJ-1 is an oocyte factor that is required for development of nuclear transfer embryos. This study presents a means for identifying natural reprogramming factors in mammalian oocytes and a unique insight into the mechanisms underlying reprogramming by nuclear transfer.