Effects of indomethacin,triamcinolone, and dexamethasone on recombinant human interleukin-1-induced substance P and prostaglandin E2 levels in rabbit knee joints

Intra-articular (i.a.) injection of recombinant human interleukin-1 alpha (rHuIL-1) in rabbit knees induced both an inflammation, as determined by increases in leukocytes in the joint fluid, and cartilage degradation, as measured by loss of proteoglycan. Substance P (SP) and prostaglandin E₂ (PGE₂) levels in the joint lavage are also elevated. Treatment with 5 mg indomethacin/kg, p.o., b.i.d., 2 mg triamcinolone i.a., and 10 mg dexamethasone/kg, p.o., reduced synovial lavage leukocyte counts, as well as PGE₂ and SP lavage concentrations induced with IL-1 injection. However, none of the treatments inhibited rHuIL-1-induced proteoglycan loss.     

Androgen receptor YAC transgenic mice carrying CAG 45 alleles show trinucleotide repeat instability

X-linked spinal and bulbar muscular atrophy (SBMA) is caused by a CAG repeat expansion in the first exon of the androgen receptor (AR) gene. Disease-associated alleles (37-66 CAGs) change in length when transmitted from parents to offspring, with a significantly greater tendency to shift size when inherited paternally. As transgenic mice carrying human AR cDNAs with 45 and 66 CAG repeats do not display repeat instability, we attempted to model trinucleotide repeat instability by generating transgenic mice with yeast artificial chromosomes (YACs) carrying AR CAG repeat expansions in their genomic context. Studies of independent lines of AR YAC transgenic mice with CAG 45 alleles reveal intergenerational instability at an overall rate of approximately 10%. We also find that the 45 CAG repeat tracts are significantly more unstable with maternal transmission and as the transmitting mother ages. Of all the CAG/CTG repeat transgenic mice produced to date the AR YAC CAG 45 mice are unstable with the smallest trinucleotide repeat mutations, suggesting that the length threshold for repeat instability in the mouse may be lowered by including the appropriate flanking human DNA sequences. By sequence-tagged site content analysis and long range mapping we determined that one unstable transgenic line has integrated an approximately 70 kb segment of the AR locus due to fragmentation of the AR YAC. Identification of the cis - acting elements that permit CAG tract instability and the trans -acting factors that modulate repeat instability in the AR YAC CAG 45 mice may provide insights into the molecular basis of trinucleotide repeat instability in humans.      

Identification and characterization of a structural protein of hepatitis B virus: a polymerase and surface fusion protein encoded by a spliced RNA

The hepatitis B virus (HBV) genome is known to contain four conserved and overlapped open reading frames (ORFs) encoding the viral core, polymerase (P), surface (S), and X proteins. Whether HBV encodes other proteins has long been a major interest in the field. Using (32)P-labeling of an introduced protein kinase A site attached to the N- or C-terminus of the HBV polymerase gene, a 43-kDa P-S fusion protein was detected in cell lysate, secreted virions, and 22-nm subviral particles. Immunobiochemical studies showed that the 43-kDa protein contains the epitopes of the N-terminus of polymerase and most parts of the surface proteins. This 43-kDa protein was shown to be a glycoprotein, similar to the surface protein. RT-PCR and sequence analyses identified a spliced mRNA which was derived from pregenomic RNA with a deletion of 454 nucleotides (nt) from nt 2447 to 2902. This splice event creates a P-S fusion ORF. This finding is consistent with the result obtained from an immunobiochemical study. Mutations at the splice donor or acceptor site on the HBV genome abrogated the production of the 43-kDa protein. These mutants had no effect on viral replication in transfected HuH-7 cells. However, this P-S fusion protein is able to substitute for the LS protein in virion maturation. On the basis of these results, we conclude that the 43-kDa protein is a polymerase-surface fusion protein encoded by a spliced RNA. Similar to the LS protein, the 43-kDa P-S fusion protein is a structural protein of HBV and might play a role in the HBV life cycle.     

Group B Streptococcal infection in neonates and colonization in pregnant women: An epidemiological retrospective analysis

Background

Group B Streptococcus (GBS) infection is one of the major causes of neonatal morbidity and mortality. Universal GBS screening with intrapartum antibiotic prophylaxis (IAP) in pregnant women were initiated in 2012 in Taiwan. This study aimed to analyze the most recent maternal GBS colonization rate and the changes in neonatal GBS infection rate from 2011 to 2016.

Behavioral characteristics of a mouse model of cancer pain

Pain is a major symptom in cancer patients, and most cancer patients with advanced or terminal cancers suffer from chronic pain related to treatment failure and/or tumor progression. In the present study, we examined the development of cancer pain in mice. Murine hepatocarcinoma cells, HCa-1, were inoculated unilaterally into the thigh or the dorsum of the foot of male C3H/HeJ mice. Four weeks after inoculation, behavioral signs were observed for mechanical allodynia, cold allodynia, and hyperalgesia using a von Frey filament, acetone, and radiant heat, respectively. Bone invasion by the tumor commenced from 7 days after inoculation of tumor cells and was evident from 14 days after inoculation. Cold allodynia but neither mechanical allodynia nor hyperalgesia was observed in mice that received an inoculation into the thigh. On the contrary, mechanical allodynia and cold allodynia, but not hyperalgesia, were developed in mice with an inoculation into the foot. Sometimes, mirror-image pain was developed in these animals. These results suggest that carcinoma cells injected into the foot of mice may develop severe chronic pain related to cancer. This animal model of pain would be useful to elucidate the mechanisms of cancer pain in humans.     

Vertical root fracture in endodontically versus nonendodontically treated teeth: a survey of 315 cases in Chinese patients

OBJECTIVE: The purpose of this study was to compare endodontically versus nonendodontically treated teeth with respect to clinical features, including patient age and gender and tooth types of vertical root fractures. STUDY DESIGN: A total of 315 consecutive cases of vertical root fracture occurring in 274 Chinese patients during a 1 3-year period were reviewed. Age and gender, as well as tooth type and root distribution of vertical root fractures, were presented and compared in endodontically versus nonendodontically treated teeth. RESULTS: Most patients (87%) had 1 fractured tooth; the others had 2 or 3 fractured teeth. Of all vertical root fractures, 40% occurred in nonendodontically treated teeth. In comparison with those in endodontically treated teeth, vertical root fractures in nonendodontically treated teeth tended to occur in patients with a higher mean age (55 years vs. 51 years) and were more frequent in male patients (78% vs. 58%). Vertical root fractures occurred in nonendodontically treated teeth more often in molars (84% vs. 53%), less often in premolars (16% vs. 33%), and seldom in anteriors (1 tooth vs. 27 teeth). CONCLUSIONS: Vertical root fractures in nonendodontically treated teeth are not uncommon and comprise a large proportion of such fractures in Chinese patients. Differences between endodontically and nonendodontically treated teeth in patient age and gender, as well as in tooth types of vertical root fractures, were demonstrated.     

Changes in hemodynamics of the carotid and middle cerebral arteries before and after endoscopic sympathectomy in patients with palmar hyperhidrosis: preliminary results

OBJECT: The purpose of this study was to analyze the change in carotid and middle cerebral artery (MCA) hemodynamics before and after endoscopic upper thoracic sympathectomy in patients with palmar hyperhidrosis (PH). METHODS: Sixty-eight patients with PH (35 males and 33 females) for whom the average age was 24.5+/-10.7 years (+/- standard deviation) were recruited into this study. These patients all underwent routine upper T-2 sympathectomy to treat their PH. Ultrasonography studies of the carotid arteries (CAs) and MCA were obtained in each patient before and after T-2 sympathectomy. The blood flow volume, flow velocity, and resistivity index (RI) in the bilateral common CAs (CCAs), internal CAs (ICAs), and external CAs (ECAs) were evaluated using duplex ultrasonography. The systolic peak velocity, mean velocity, diastolic peak velocity, pulsatility index, and RI of the bilateral MCAs were evaluated using transcranial Doppler ultrasonography. Blood pressure and heart rate were also recorded during this study. The Student paired t-test was used to analyze the differences between studies before and after bilateral T-2 sympathectomy. There was a significant reduction in diastolic pressure after T-2 sympathectomy (p = 0.003), but not in systolic pressure or heart rate. The vessel diameter was increased after sympathectomy in the left CAs and right CCA. The T-2 sympathectomy led to significant elevation of blood flow volume and RI in the left CCA, ICA, and ECA (p < 0.05). The authors found significant increases in maximum flow velocity and RI in the left MCA (p < 0.05). CONCLUSIONS: Patients who underwent T-2 sympathectomy demonstrated a significant increase in blood flow volume and flow velocities of the CAs and MCA, especially on the left side. Asymmetry of sympathetic influence on the hemodynamics of the CAs and MCA was noted. The usefulness of sympathectomy for the treatment of ischemic cardiovascular and cerebrovascular disease deserves further investigation.     

Telomerase activity is a useful marker to distinguish malignant pancreatic cystic tumors from benign neoplasms and pseudocysts

BACKGROUND: Pancreatic serous cystadenoma, mucinous cystic neoplasms, ductal adenocarcinoma with cystic change, and pseudocysts are a spectrum of pancreatic cystic lesions. Their management strategy and prognosis are extremely diverse. Imaging study, cytology, and analysis of the tumor markers of cyst fluid are not always reliable in differentiation of these disease entities. MATERIALS AND METHODS: Fifteen patients with pancreatic cystic neoplasms (including six mucinous cystadenocarcinomas, two mucinous cystic neoplasms with borderline malignancy, two mucinous cystadenomas, and five serous cystadenomas), 4 patients with pancreatic ductal adenocarcinomas with cystic change, and 10 patients with pseudocysts were studied. Echo-guided or computed tomography-guided biopsies of pancreatic cystic lesions and their normal counterparts were conducted on all patients prior to operation or other management. The specimens were assayed for telomerase activity by using TRAP (telomere repeat amplification protocol). The level of telomerase activity in each specimen was semiquantitated as strong, moderate, weak, and none. The final diagnoses were made from histopathological examination of surgically resected or biopsied specimens. The efficacy of telomerase activity as a tumor marker to predict malignancy of pancreatic cystic lesions was evaluated. RESULTS: Three of the four pancreatic ductal adenocarcinomas with cystic change had strong or moderate telomerase activity; four of the six mucinous cystadenocarcinomas had moderate or weak telomerase activity; one of the two mucinous cystadenomas with borderline malignancy had weak telomerase activity; and none of their normal counterparts had detectable telomerase activity. In contrast, none of the two mucinous cystadenomas, five serous cystadenomas, and 10 pseudocysts had detectable telomerase activity. Based on these results, the sensitivity of telomerase activity for prediction of malignancy or premalignancy of pancreatic cystic lesions was 67%, the specificity was 100%, and the positive and negative predictive values were 1.0 and 0.81, respectively. The overall accuracy was 86%. CONCLUSIONS: The differential expressions of telomerase activity have been detected specifically in malignant and premalignant pancreatic cystic tumors, but not in benign cystic neoplasms or pseudocysts. The implications of these results are that telomerase activation takes part in the malignant transformation of pancreatic cystic neoplasms and that telomerase activity is a useful marker to distinguish malignant pancreatic cystic tumors from benign neoplasms and pseudocysts.