Relationship between Plasma Fibrinogen Levels and Pulmonary Function in the Japanese Population: The Takahata Study

Background:Plasma fibrinogen is considered a biomarker of respiratory disease, owing to the relationship between plasma fibrinogen and pulmonary function established in Western populations. However, such a relationship has not yet been confirmed in an Asian population. We assessed this relationship in the general Japanese population.Methods:Totally, 3,257 men and women aged ≥40 years who participated in a community-based annual health checkup in Takahata, Japan, from 2004 to 2006, underwent spirometry, and their plasma fibrinogen levels were determined.Results:We found an inverse relationship between spirometric measures (percent predicted forced vital capacity [%FVC] and forced expiratory volume in 1s [%FEV₁], and FEV₁/FVC) and plasma fibrinogen levels in men, but not in women. The plasma fibrinogen levels were significantly higher in subjects with restrictive, obstructive, and mixed ventilatory disorders than in those with normal spirometry results. Multiple linear regression analysis revealed that in men, plasma fibrinogen levels were predictive for %FVC and %FEV₁ (independent of age, body mass index, and cigarette smoking) but not for FEV₁/FVC.Conclusions:Plasma fibrinogen was significantly associated with pulmonary function in Japanese men, and as such, plasma fibrinogen might be a potent biomarker for pulmonary dysfunction in men.     

Fibroblast growth factor 23 enhances renal klotho abundance

Klotho constitutes the receptor for fibroblast growth factor 23 (FGF23). However, the effects of FGF23 on renal and circulating klotho are not well-known. In vivo experiments were performed to assess the effects of FGF23 (10 μg/kg), parathyroid hormone (PTH, 10 μg/kg), and 1,25-dihydroxy-vitamin D3 (1,25VD, 1 μg/kg) on renal expression and serum concentration of klotho in Wistar rats. Phosphate excretion was increased at 3 h after FGF23 administration (p?<?0.05). Renal klotho expressions and serum klotho levels were elevated at 3 h (p?<?0.01) by FGF23. At 24 h, phosphate excretion was still elevated (p?<?0.05), and serum phosphate, 1,25VD, and PTH were reduced (p?<?0.05). However, serum and renal klotho returned to the control level at 24 h. PTH markedly increased phosphate excretion after 24 h (p?<?0.01). There were increases in FGF23 at 3 and 24 h, and 1,25VD at 24 h after PTH administration (p?<?0.05). Serum klotho concentration and renal klotho expression were elevated by PTH at 3 or 24 h. After 24 h of exposure to 1,25VD, considerable increases in serum FGF23, calcium, and phosphate were seen (p?<?0.05), but PTH was decreased (p?<?0.01). 1,25 VD elevated renal klotho expression and serum klotho (p?<?0.05) at 3 h, but returned to control levels at 24 h. Our data indicate that FGF23 rapidly increases renal klotho expression and serum klotho. The present findings are consistent with the notion that PTH increases phosphate excretion at least in part through elevations of FGF23 and klotho. Moreover, our results suggest that 1,25VD increases klotho expression independently of FGF23.     

Early infectious complications after peripheral blood stem cell autografts in children

Seventeen children underwent marrowablative high-dose chemotherapy with peripheral blood stem cell autografts and were studied retrospectively to determine the type, frequency, and outcomes associated with infectious complications 3 months postgraft. The patients were kept in isolated rooms with a laminar air flow facility, but no decontamination procedures, such as gut sterilization with nonabsorbable antibiotics, nonmicrobial diet, and skin cleansing, were used. They were under their mothers' daily care to maintain good psychological conditions. After the completion of marrow-ablative chemotherapy and the infusion of stem cells, the absolute granulocyte count exceeded 0.5 × 10⁹/liter with a mean of 17.9 days (range 6–65 days), Fifteen patients developed a total of 16 febrile episodes during the first 4 week period, and the confirmed diagnoses were mucositis (12), enterocolitis (nine), septicemia (four), central venous catheter-associated infection (three), pneumonia (one), perianal abscess (one), and possible invasive fungal infection (one). All episodes were successfully treated with parenteral antibiotic therapy, and no patient died of infectious complications. The observations suggest that high-dose chemotherapy can be performed safely with simple and efficient patient management protocol followed by peripheral blood stem cell autografts.     

p53 mutations in early neoplastic lesions of the urinary bladder in rats treated with N-butyl-N-(4-hydroxybutyl)nitrosamine

Rat experimental models using Ar-butyl-Af-(4-hydroxybutyl) nitrosamine(BBN) as an initiating agent have been widely used to studycarcinogenic processes in the urinary bladder. In this study,early neoplastic lesions from 10 male F344 rats treated with0.05% BBN for 16 weeks were analyzed for changes in the H-rasor p53 genes by polymerase chain reaction (PCR)-single strandconformation polymorphism (SSCP) analysis and subsequent DNAsequencing. Lesions were pooled for each of the 10 rats andsix showed point mutations in the p53 gene and one in the H-rasgene. These results would indicate that BBNinduced rat urinarybladder carcinomas are similar to human urinary bladder carcinomaswith respect to alterations in the p53 and H-ras genes and thatp53 gene alterations are relatively early events in rat urinarybladder carcinogenesis induced by BBN treatment     

Detection of Epstein-Barr virus DNA from a lymphoma-like lesion of the uterine cervix.

The case of a 60-year-old woman in whom a lymphoma-like lesion of the cervix was found during an episode of silent Epstein-Barr virus (EBV) infection is presented. Fractional curettage was performed because of abnormal endometrial smear. The endocervical curettage specimens were diagnosed as highly suggestive of malignant lymphoma, but microscopic examination of a subsequent hysterectomy specimen revealed a benign lymphoid hyperplasia. Those were retrospectively interpreted as a lymphoma-like lesion of the cervix. In the absence of clinical symptoms of infectious mononucleosis, the results of serologic tests for EBV revealed an active EBV infection. EBV DNA was demonstrated in nuclei of large lymphoid cells in endocervical curettage specimens by in situ hybridization. She is alive and well 32 months postoperatively. When female patients with lymphoma-like lesions of the lower genital tract are encountered, examinations for EBV are recommended.     

Frequent mutations of the p53 gene and infrequent H- and K-ras mutations in urinary bladder carcinomas of NON/Shi mice treated with N-butyl-N-(4-hydroxybutyl)nitrosamine

To elucidate whether common genetic events in human urinarybladder carcinogenesis also occur in rodent models, we investigatedthe presence of p53, H- and K-ras mutations in 18 urinary bladdercarcinomas induced by various concentrations of N-butyl-N-(4-hydroxybutyl)nitrosamine(BBN) in male NON/Shi mice. Histopathologically, all were invasive,11 being squamous cell carcinomas (SCCs) and the remaining sevenbeing transitional cell carcinomas (TCCs). Using polymerasechain reaction single-strand conformation polymorphism (PCR-SSCP)analysis followed by DNA sequencing, p53, H- and K-ras mutationswere observed in 14 (78%; exons 5–7), two (11%; one eachon exons 1 and 2) and one (5.6%; exon 1) animals respectively.The frequencies of mutations in p53 exons 5, 6 and 7 were 7(39%), 4 (22%), and 9 (50%) respectively, and no mutation wasfound in exon 8. All mutations involved one base-pair substitutionwith or without amino acid changes and the types of base-pairsubstitution were random. No evident association was observedbetween mutation sites and the histological phenotypes. In conclusion,p53 mutations are frequent in BBN-induced mouse invasive urinarybladder tumors, at similar levels to those observed for humanhigh-grade invasive carcinomas, and this plus their distributionsuggests their possible participation in this model of urinarybladder carcinogenesis.     

Screening of various plant extracts used in ayurvedic medicine for inhibitory effects on human immunodeficiency virus type 1 (HIV-1) protease

To identify substances with anti-human immunodeficiency virus (HIV) activity in traditional medicines, water and methanol extracts of crude drugs used in Indian traditional medicine (Ayurveda) were subjected to screening for their inhibitory effects on HIV type 1 protease (PR). The enzyme activity was determined by HPLC and of the 39 crude drugs tested, the extracts of the seeds of Areca catechu, the bark of Eugenia jambolana, the bark of Saraca indica and the stem bark of Terminalia arjuna inhibited the HIV-1 PR activity by more than 70% at a concentration of 0.2 mg/mL. The most potent inhibition was shown by the A. catechu extract, from which some procyanidins were isolated. One of them, arecatannin B1 showed significant HIV-1-PR inhibitory activity.     

The development of three dimensional video microscope system for clinical application in neurosurgery

OBJECTIVE: The employment of surgical microscopy in the field of neurosurgery has significantly contributed not only to the advancement of surgical technique, but also the operative outcome as well. This technology has allowed surgeons to meet the demands for increasingly difficult levels of surgery, which usually require a long operative time. However, the surgeon and the assistant are restricted in their posture for a long time, leading to excessive muscular and ocular stress. To solve these problems, we have developed and clinically applied a three dimensional video microscope system for surgery, using a two binocular camera method, that allows surgical procedures to be performed over a video monitor. METHOD: Two 3CCD cameras were installed on the assistant's lens attachment and the camera lens attachment of the microscope for neurosurgery, manufactured by Carl Zeiss Co., Ltd. The surgery was performed by viewing the three dimensional picture on the monitor, which was created by processing the images from the cameras by a time-division method. In November 1998, the prototype was completed and, with numerous modifications, its clinical application has become possible. Currently, we have used it in 42 clinical cases. RESULTS: 1) Instead of viewing the surgical field through a conventional surgical microscope, the surgeon and the assistant were able to perform microsurgery by viewing the stereoscopic vision on the video monitor, through polarized glasses. 2) The assistant is provided with a separate video monitor, so that the assistant can freely adjust the angle of vision 90-180 degrees, according to where he stands. 3) The nurses, resident surgeons and students can view the same three dimensional images displayed to the surgeon. This effectively contributes to the educational environment. CONCLUSION: Even during a long surgical procedure, the posture of surgeon and assistant became less restricted since there was no need to look through the eyepiece of the microscope and led to significant decrease in physical fatigue and ocular strain. In the 42 clinical trials, the operation proceeded uneventfully, without any serious complications.