Effects of long-term and reduced-dose hormone replacement therapy on endothelial function and intima-media thickness in postmenopausal women.

OBJECTIVE: Short-term estrogen therapy improves endothelial function in postmenopausal women. However, there are few reports on its long-term effects on endothelial function and carotid intima-media thickness. Further, we determined whether a reduced dosage of estrogen may maintain its beneficial effects. DESIGN: Eighteen postmenopausal women (53.7+/-1.1 years) who had been diagnosed as having osteoporosis were enrolled. Among them, 11 women were prescribed oral conjugated estrogen 0.625 mg and medroxyprogesterone acetate 2.5 mg per day, and 7 women were prescribed an oral calcium supplement as the control group. Each patient decided whether she would take hormone replacement therapy or a calcium supplement. We performed ultrasound measurement of endothelial function of the brachial artery and carotid intima-media thickness. Examinations were scheduled to be performed pre-therapy and after 3, 6, 12, 18, 24, and 36 months of therapy. RESULTS: After three years of therapy, 6 women in the hormone replacement therapy group agreed to take half the dose of oral conjugated estrogen. Improvement of flow-mediated dilatation was observed at 3 months and the improvement was preserved up to 36 months. A similar improvement was also observed while women were on hormone replacement therapy even at the reduced dosage. Intima-media thickness of the common carotid artery in the control group increased after 12 months, which was not observed in the hormone replacement therapy group. CONCLUSIONS: Our results indicate that even at half the dose of estrogen, hormone replacement therapy may improve endothelial function and prevent the progression of carotid intima-media thickening in postmenopausal women.     

Albumin and urea production by hepatocytes cultured on extracellular matrix proteins-conjugated poly(vinyl alcohol) membranes

Production of albumin and urea by mouse hepatocytes on poly(vinylalcohol-co-ethylamine) (PVA-EA) membranes containing immobilized extracellular matrix (ECM) proteins was investigated for 7 days. The amount of ECM proteins (collagen, vitronectin and laminin) immobilized on PVA-EA and PVA-ECM membranes was determined to range from 1.09 microg/cm2 to 1.60 microg/cm2. Hepatocytes cultured on PVA-ECM membranes in serum-free media showed higher albumin production than those cultured on PVA-EA membranes after a 7-day incubation under the conditions in this study. Urea production by hepatocytes on PVA-ECM membranes was also determined to be higher than that on PVA-EA membranes up until day 5 of incubation in serum-free media, whereas no difference of urea production by hepatocytes on different PVA-ECM membranes and PVA-EA membranes was observed at 7 days of incubation. The effect of ECM proteins in PVA-ECM membranes on hepatocyte function (such as albumin and urea production) was observed in hepatocytes cultured in serum-free media up to day 5 of incubation. The ECM proteins immobilized on the PVA-ECM membranes contributed not only to the long-term stable production of albumin and urea by hepatocytes, but also the improved surviVal (viability) of hepatocytes on PVA-ECM membranes.     

Experimental Mucosal Infection with Molecularly Cloned Feline Immunodeficiency Viruses

Four of six specific pathogen-free cats were infected after intravaginal exposure to molecularly cloned lymphotropic but non-Crandell feline kidney (CRFK)-tropic feline immunodeficiency virus strain TM2 and its AP-1 deletion mutant. The sequences of the env V3-to-V5 region which defines the CRFK tropism were unchanged in the infected cats through the infection. These data suggest that the strain was transmitted across the mucosal epithelium without a broadening of cell tropism.     

The synchronization of chemotherapy to circadian rhythms and irradiation in pre-operative chemoradiation therapy with hyperthermia for local advanced rectal cancer.

PURPOSE: The therapeutic and adverse effects of pre-operative chrono-chemoradiation with local hyperthermia for patients with rectal adenocarcinoma were evaluated. MATERIALS AND METHODS: Pre-operative radiation therapy of a total dose of 40 Gy (n = 10) or 50 Gy (n = 19) on the whole pelvis and hyperthermia once a week during the radiation therapy for 1 h were performed for patients with T2-T4 rectal adenocarcinoma. Chemotherapy consisted of 5-FU (250 mg m-2 per day) and LV (25 mg m-2 per day) administered by continuous infusion in the night for 5 days a week in the second and fourth weeks of radiation. RESULTS: Grade 3+ toxicities were seen only in two patients (6.9%). A significant down staging was seen in 41.4% of all cases and 52.6% of cases with a radiation dose of 50 Gy. Of the patients who had received surgical resection of a tumour, three (11.1%) had no residue pathologically in the specimen and eight (29.6%) had microscopic lesions. CONCLUSIONS: These results yielded a high response rate with minimal toxicities for advanced low-rectal adenocarcinoma. The administration of 5-FU during the sleeping time before irradiation might have an advantage not only as a chronotherapy but also as a radiation sensitizer.     

Association of bone mineral density with polymorphism of the human matrix Gla protein locus in elderly women

The contribution of genetic factors has been implicated in the determination of bone mass in twin and family studies. Some of the genes involved would regulate bone metabolism, bone formation, and resorption, all processes that determine bone mass. One candidate gene, matrix Gla protein gene (MGP), has been implicated in the pathogenesis of bone loss through a repression of bone formation. To analyze the genetic background for osteoporosis in elderly women, we have investigated a possible association between the CA repeat polymorphism at the human MGP gene locus and bone mineral density (BMD) of radial bone in 460 elderly Japanese women. Genotypes were classified into six groups according to the number of CA repeats present, from 13 to 18 (alleles A1 through A6). BMD was expressed as the adjusted BMD (ADJBMD), which was the body mass index (BMI)- and age-adjusted average BMD. The 214 women who lacked an A2 allele (212 bp, containing 17 repeats of CA) had significantly lower adjusted BMD than the participants (n = 246) who possessed an allele of that size (mean ± SD; 0.303 ± 0.062 vs 0.315 ± 0.062 g/cm²; P = 0.0382). This result suggests that genetic variation at the MGP locus is associated with some determinants for BMD in elderly women. Therefore, this locus should serve as one of the genetic markers for osteoporosis. Received: Jan. 7, 1999 / Accepted: June 17, 1999     

Detailed Evolutionary Analyses of the F Gene in the Respiratory Syncytial Virus Subgroup A

We performed evolution, phylodynamics, and reinfection-related antigenicity analyses of respiratory syncytial virus subgroup A (RSV-A) fusion (F) gene in globally collected strains (1465 strains) using authentic bioinformatics methods. The time-scaled evolutionary tree using the Bayesian Markov chain Monte Carlo method estimated that a common ancestor of the RSV-A, RSV-B, and bovine-RSV diverged at around 450 years ago, and RSV-A and RSV-B diverged around 250 years ago. Finally, the RSV-A F gene formed eight genotypes (GA1-GA7 and NA1) over the last 80 years. Phylodynamics of RSV-A F gene, including all genotype strains, increased twice in the 1990s and 2010s, while patterns of each RSV-A genotype were different. Phylogenetic distance analysis suggested that the genetic distances of the strains were relatively short (less than 0.05). No positive selection sites were estimated, while many negative selection sites were found. Moreover, the F protein 3D structure mapping and conformational epitope analysis implied that the conformational epitopes did not correspond to the neutralizing antibody binding sites of the F protein. These results suggested that the RSV-A F gene is relatively conserved, and mismatches between conformational epitopes and neutralizing antibody binding sites of the F protein are responsible for the virus reinfection.     

Catheterization of the pulmonary artery using a 3 French catheter in patients with congenital heart disease

A 3 French (3F) coaxial polyurethane catheter was utilized for catheterization of the pulmonary artery in patients with complex congenital heart disease with concomitant stenosis or atresia of the pulmonary valve, with or without Blalock-Taussig shunts. Mean aortic and atrial pressures measured with the 3F catheter were compared with those measured with 5–6F conventional catheters. The values measured with the 3F catheter were identical to those measured with 5–6F catheters. Mean pulmonary arterial pressure measured using the 3F catheter was significantly higher than that measured using the 5–6F catheters, but it was not significantly different from mean pulmonary venous wedge pressure. Of 43 patients, 5–6F conventional catheters could be inserted into the branch pulmonary artery in 22 patients, but the 3F catheter could be inserted into the pulmonary artery in all patients. These data suggest that the 3F catheter is useful for catheterization in patients with complex congenital heart disease associated with pulmonary atresia or severe pulmonary stenosis. Cathet. Cardiovasc. Diagn. 45:45–50, 1998. © 1998 Wiley-Liss, Inc.     

Association between dyspeptic symptoms and endoscopic findings based on the Kyoto classification of gastritis in Japanese male

The Kyoto gastritis classification is used to categorize the endoscopic characteristics of Helicobacter pylori infection-associated gastritis. We aimed to clarify the association among endoscopic findings and abdominal dyspeptic symptoms in Japanese male. We administered a questionnaire to 418 subjects who underwent endoscopy as part of a health check-up from August 2003 to April 2004 to investigate the association among endoscopic findings of the Kyoto classification and the presence of dyspeptic symptoms. Logistic regression analyses were performed to evaluate risk based on dyspeptic symptoms. Among 418 health check-up subjects, 21.3% (89/418) reported dyspeptic symptoms in the questionnaire. The incidence of fundic gland polyp among patients with dyspeptic symptoms was 12.4% (11/89), which was significantly higher than that among non-symptomatic subjects (4.3%, 14/329, p = 0.004). Logistic regression analyses showed that fundic gland polyp was a risk factor for dyspeptic symptoms [odds ratio (OR): 3.413, 95% confidence interval (CI): 1.430–8.142], while short-segment Barrett’s esophagus and male sex were protective factors (OR: 0.569, 95% CI: 0.349–0.928 and OR: 0.333, 95% CI: 0.117–0.948, respectively). In conclusion, Endoscopic findings of fundic gland polyp may be associated with dyspeptic symptoms, which in turn may be a useful marker of gastric condition.     

Periodontal Tissue as a Biomaterial for Hard-Tissue Regeneration following bmp-2 Gene Transfer

The application of periodontal tissue in regenerative medicine has gained increasing interest since it has a high potential to induce hard-tissue regeneration, and is easy to handle and graft to other areas of the oral cavity or tissues. Additionally, bone morphogenetic protein-2 (BMP-2) has a high potential to induce the differentiation of mesenchymal stem cells into osteogenic cells. We previously developed a system for a gene transfer to the periodontal tissues in animal models. In this study, we aimed to reveal the potential and efficiency of periodontal tissue as a biomaterial for hard-tissue regeneration following a bmp-2 gene transfer. A non-viral expression vector carrying bmp-2 was injected into the palate of the periodontal tissues of Wistar rats, followed by electroporation. The periodontal tissues were analyzed through bone morphometric analyses, including mineral apposition rate (MAR) determination and collagen micro-arrangement, which is a bone quality parameter, before and after a gene transfer. The MAR was significantly higher 3–6 d after the gene transfer than that before the gene transfer. Collagen orientation was normally maintained even after the bmp-2 gene transfer, suggesting that the bmp-2 gene transfer has no adverse effects on bone quality. Our results suggest that periodontal tissue electroporated with bmp-2 could be a novel biomaterial candidate for hard-tissue regeneration therapy.     

Current status of oral antidiabetic drug prescribing patterns based on the body mass index for Japanese type 2 diabetes mellitus patients and yearly changes in diabetologists' prescribing patterns from 2002 to 2019 (JDDM61)

Aims/IntroductionType 2 diabetes mellitus is caused by a relative imbalance between insulin secretion and sensitivity related to the body mass index (BMI). Seven categories of oral antidiabetic drugs (OADs) are available in Japan. It is important to assess the OAD utilization patterns based on patients’ BMI levels.Materials and methodsOAD prescribing patterns from 2002 to 2019 were analyzed using the data collected in the computerized diabetes care database provided by the Japan Diabetes Clinical Data Management Study Group; OAD utilization patterns in 25,751 OAD‐treated type 2 diabetes mellitus patients registered in 2019 were analyzed after classifying them into five categories of BMI.ResultsComparing OAD usage between 2002 and 2019, sulfonylureas decreased from 44.5 to 23.2%, and biguanides (BGs) increased from 19.3 to 50.3%. Dipeptidyl peptidase‐4 inhibitors (DPP4is) increased to 56.9% in 2019. Sodium–glucose cotransporter 2 inhibitors (SGLT2is) increased to 23.6% in 2019. About 90% of type 2 diabetes mellitus patients had BMI < 30 kg/m². DPP4is were the most used OADs in 2019. When BMI exceeded 30 kg/m², use of BGs and sodium–glucose cotransporter 2 inhibitors increased, and use of sulfonylureas and DPP4is decreased. Although DPP4is were the most used OADs for patients with BMI <30 kg/m², they were the third most prescribed OADs for patients with BMI >35 kg/m² after BGs and sodium–glucose cotransporter 2 inhibitors .ConclusionsDPP4i usage was as high as that of BG in the analysis of Japanese type 2 diabetes mellitus patients with relatively low BMI. This was considered to be a treatment option appropriate for the pathophysiology in Japanese patients.