Dental impact of anti-fibroblast growth factor 23 therapy in X-linked hypophosphatemia / 国际口腔科学杂志·英文版

Elevated fibroblast growth factor 23 (FGF23) in X-linked hypophosphatemia (XLH) results in rickets and phosphate wasting, manifesting by severe bone and dental abnormalities. Burosumab, a FGF23-neutralizing antibody, an alternative to conventional treatment (phosphorus and active vitamin D analogs), showed significant improvement in the long bone phenotype. Here, we examined whether FGF23 antibody (FGF23-mAb) also improved the dentoalveolar features associated with XLH. Four-week-old male Hyp mice were injected weekly with 4 or 16 mg·kg-1 of FGF23-mAb for 2 months and compared to wild-type (WT) and vehicle (PBS) treated Hyp mice (n = 3-7 mice). Micro-CT analyses showed that both doses of FGF23-mAb restored dentin/cementum volume and corrected the enlarged pulp volume in Hyp mice, the higher concentration resulting in a rescue similar to WT levels. FGF23-mAb treatment also improved alveolar bone volume fraction and mineral density compared to vehicle-treated ones. Histology revealed improved mineralization of the dentoalveolar tissues, with a decreased amount of osteoid, predentin and cementoid. Better periodontal ligament attachment was also observed, evidenced by restoration of the acellular cementum. These preclinical data were consistent with the retrospective analysis of two patients with XLH showing that burosumab treatment improved oral features. Taken together, our data show that the dentoalveolar tissues are greatly improved by FGF23-mAb treatment, heralding its benefit in clinics for dental abnormalities.

Anti-allergic effects of the probiotic preparations of enterococcus on experimental allergic rhinitis in mice / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>The aim of this study was to investigate the anti-allergic effects of lysozyme/heat-treated Enterococcus faecalis FK-23 (LFK) and heat-treated Enterococcus faecium sp. TN-3 (TN) on experimental allergic rhinitis (AR).</p><p><b>METHODS</b>A total of twenty-four BALB/c mice were divided into four groups randomly: (1) positive control group, (2) LFK-fed group, (3) TN-fed group, and (4) negative control group. To establish the murine AR model, intraperitoneal injection and nasal drip with ovalbumin (OVA) were performed. Saline was used instead of OVA for negative control. Probiotic preparations of LFK and TN were orally administrated for 42 days [60 mg (0.5 ml)/d] in LFK-fed and TN-fed mice, respectively. The positive and negative control mice received saline orally for 42 days. Nasal rubbing and sneezing were monitored on d 21, d 27, and d 35. After the final challenge, mice were sacrificed on d 42, and eosinophilic infiltration into the nasal mucosa was quantified (H&E stain). IFN-gamma, IL4 and OVA-specific IgE levels in the sera and splenocyte culture supernatants were determined by ELISA kits.</p><p><b>RESULTS</b>Nasal rubbing of LFK-fed mice was significantly reduced compared to the positive control group on day 27 (t = 2.95, P = 0.028). Both in the LFK-fed and TN-fed mice, nasal rubbing (t value was 3.75 and 3.06, P value was 0.005 and 0.011, respectively) and sneezing (t value was 2.56 and 3.35, P value was 0.038 and 0. 01, respectively) were significantly decreased compared to the positive control group on d 35. The H&E strain section of nasal tissue showed that eosinophil influx into the nasal mucosa decreased significantly both in the LFK-fed and TN-fed mice compared to the positive control group on day 42 (t value was 3.44 and 2.97, P value was 0.014 and 0.025, respectively); however, the LFK-fed mice and TN-fed mice had significant eosinophil influx into the nasal mucosa than that in the negative control group (t value was 2.54 and 3.39, P value was 0.044 and 0.015, respectively). There were no significant differences in the serum levels of IL-4 and OVA-specific IgE, as well as the levels of IFN-gamma and IL-4 in splenocyte culture supernatants between the LFK-fed group and positive control group on d 42 (all P > 0.05). Interestingly, the TN-fed mice had significantly higher serum levels of IFN-gamma compared to the LFK-fed mice [TN-fed mice: (27.07 +/- 3.83) pg/ml, LFK-fed mice: (14.83 +/- 0.99) pg/ml; Z = 2.49, P = 0.016], but not the negative control group [negative control group: (37.12 +/- 1.65) pg/ml; Z = 1.18, P = 0.343] on day 42. The serum levels of IL-4 were significantly lower in the TN-fed mice than those in the positive control group [TN-fed mice: (34.48 +/- 7.53) pg/ml, positive control group: (58.68 +/- 6.59) pg/ml; Z = 2.11, P = 0.035]; however, the levels were significantly higher in the TN-fed mice than those in the negative control group [negative control group: (20.22 +/- 1.75) pg/ml; Z = 2. 31, P = 0.021]. The TN-fed mice had significantly higher levels of IFN-gamma in splenocyte culture supernatants compared to the LFK-fed mice (Z = 2.72, P = 0.03) and the positive control group (Z = 2.30, P = 0.029), whilst the splenocyte culture supernatant levels of IL-4 (Z = 2.12, P = 0.034) and the serum levels of OVA-specific IgE (Z = 2.31, P = 0.021) were significantly lower in the TN-fed mice compared to the positive control mice.</p><p><b>CONCLUSIONS</b>It is suggested that oral administration of probiotic LFK or TN may alleviate nasal symptoms and reduce nasal eosinophilia in the murine AR model. TN supplementation has obviously regulatory effects on the cytokine levels of IFN-gamma and IL-4, and significantly inhibitory effects on antigen-specific IgE levels.</p>

DNA Sequence Analysis of HPV type 33 in the Genital Tract of Woman / Шинэ санаа Шинэ нээлт

Our present study investigated DNA sequence analysis of Human Papillomavirus (HPV) typc-33 in sexually active women. In present study 22 HPV-33 positive Endocervical specimens were obtained by use of Polymerase Chain Reaction (PCR), from total 500 participants, and further analyzed by DNA sequencing of the Long Control Region (LCR), E6 and E7 genes. For the genes LCR and E6 13 samples, for the gene E7 all 22 HPV-33 positive samples were sequenced by Applied Biosystcms. All 22 HPV-33 positive participants were Mongolian nationality. Most common Non-prototype-Likc variant in LCR is HPV-33 LCR-17 (11/13). one HPV-33 LCR-5 (1/13), and only one Prototype was found (1/13). In the E6, 12 samples were variant 33-E6-6 (12/13), and one prototype was found. lntheE7, 13 Prototype (13/22), 11 Non-prototype-Like variants were found. From the sequence result of gene sites in LCR, E6 and E7 most common HPV-33 variant in Mongolia is MN-17-6-0 (10/13), HPV-33 MN-0-6-0 (1/13), HPV-33 MN-5-6-0 (1/13) and one Montreal variant were found HPV-33 MT-17-0-0 (1/13). We identified 3 new variants of 11PV-33 which we called MN (Mongolia). From sequence result in 3 sites of genes, LCR is more variable compare with E6 and E7. F.6 were variable compare with E7. ' ' Health Sciences University of Mongolia, Ulaanhaatar, Mongolia 4,6 Department of Biochemistry and Molecular Biology, Nippon Medical School, Tokyo. Japan

Clinical Genetics Education Program in Medical School: A Trial in Nippon Medical School / 医学教育

Advances in genetic medicine has rapidly been applied to clinical practice. However, many medical students have not studied biology or genetics in high school. There is little chance to think in Japan medical education about how to treat genetic information appropriately in the setting of clinical medicine. The timing and contents of a clinical genetics education program in medical school has hardly been discussed in Japan. This paper discusses the clinical genetics educationduring the medical-science and clinical-medicine stages at Nippon Medical School.<BR>1) An exercise on information gathering and role-play (for 180 minutes) about color vision deficiency were performed during the second-year molecular genetics course.<BR>2) A clinical genetics course (45 minutes 18 classes) in the fourth year was started in 2002 as a part of an integrated medical curriculum with courses classified by organ system.<BR>3) This clinical genetics course included systematic lectures for knowledge acquisition, lectures by patient support groups, exercises in drawing pedigrees, role-play, and discussions of ethical issues. Students evaluated this course favorably.<BR>4) Some topics in clinical genetics can be effectively presented at an early stage of medical education as part of an introduction to medicine. To maximize the educational effects and increase the possibility that students understand the importance of medical genetics, clinical genetics education in medical school will be performed after the student have grasped a basic understanding of diseases through lectures about clinical subjects.

A Questionnaire Study of Medical Students' Comprehension of Clinical Genetics: The Necessity of Education in Clinical Genetics in Medical School / 医学教育

Because of the rapid progress in genetic research, only a small part of what is known about clinical genetics is taught in medical schools. At Nippon Medical School a clinical genetics course for fourth-year students started in October 2002. In the present study, we used a questionnaire to investigate how well second-year medical school students understand clinical genetics. The results of the questionnaire suggested that many students are confused about basic concepts in clinical genetics, such as the differences between inherited disease and diseased caused by genetic disorders and between hereditary and chromosomal disorders and also suggested that education in clinical genetics is needed in medical schools. In the United States, guidelines for teaching genetics in medical schools have been established. However, in Japan, considering the lack of consensus about medical genetics terminology, to disseminate correct knowledge about clinical genetics, the present situation of medical genetics education in medical schools must be clarified, and various other measures, such as establishing what information should be taught, should be carried out.

Three Cases Report of Chugoho-Honton-to / 日本東洋医学雑誌

Case 1 was a 70-year-old female patient who visited our Department mainly due to palpitations which had persisted for the previous four years. From about one year ago, paroxysmal palpitations have occurred frequently. The 24-hour Holter ECG monitoring and echocardiography indicated supraventricular arrhythmia, but there was no temporal association between the arrhythmia and the palpitations. She was very nervous and irritable. She felt fullness of the upper abdomen and palpitations in the lower abdomen. She was given Chugoho-honton-to-ka-bukuryo-byakujutsu. One week later, the palpitations became less frequent, and two weeks later they all but disappeared.<br>Case 2 was a 41-year-old male company employee. He visited our Department complaining of general malaise, abnormal perspiration of the upper body, and pain in the fingers. Six years previously, he had developed erythema both in the palms and in the soles of the feet and also pain in the fingers of both hands. Four years ago, swelling occurred in the tips of his fingers and toes, which then aggravated. He was diagnosed as having acromegaly accompanied by pituitary adenoma and subsequently underwent resection of the pituitary tumor. After the operation, he developed general malaise and abnormal perspiration in the upper body, which obliged him to take time off work. Based on marked feelings of heat in the upper body and cold in the lower body and also abnormal sweating attacks, he was considered to be suffering from hypochondriasis with palpitation attack. One week after he was started on Chugoho-honton-to-ka-bukuryo-byakujutsu, his legs no longer felt cold. Symptoms of the joints and abnormal sweating subsequently improved, which enabled him to return to work.<br>Case 3 was a 32-year-old housewife who visited our Department complaining of headache and pain in the right shoulder. She had had contusion in the scapula ten years previously and had been suffering from dull pain ever since. Seven years ago, when she had a baby, she developed severe pain in the paraspinal muscle facing the right scapula. This severe pain radiated along the dorsal muscle and was accompanied by headache. Because she felt hot in the upper body and cold in the lower body, subjective palpations in the upper abdomen, and a mass in the hypochondria and umbilical region, Chugoho-honton-to-ka-bukuryo-byakujutsu was given. This produced excellent results.<br>Based on the experience of these three cases together with what can be found in the literature, we believe that conditions where Chugoho-honton-to-ka-bukuryo-byakujutsu are indicated have the following features. (1) The conditions are often triggered by fright, fear, depression etc. (2) There exist paroxysmal palpitations, headache, and the sensation of hot flushes. (3) A feeling of anxiety ascends from the abdomen. (4) The disease is in the initial stage of the three Yin diseases. (5) There are signs and symptoms of a deficiency in Qi. (6) There are subjective palpitations in the upper abdomen and in the epigastrium. (7) There is fullness of the upper abdomen and epigastrium, often accompanied by a mass in the hypochondria or umbilical region.