Differential expression of decorin and biglycan genes during palatogenesis in normal and retinoic acid-treated mice.

Proteoglycans are involved in secondary palate formation. In the present study, we focused on two small leucine-rich proteoglycans, decorin and biglycan, because they assembled extracellular matrix molecules such as collagens and modulated signaling pathway of transforming growth factor-beta. To investigate the functions of decorin and biglycan in palatogenesis, we compared their mRNA expression patterns between normal palate and retinoic acid-induced cleft palate in mice by using in situ hybridization analysis during the period of embryonic day 13.5 (E13.5) to E15.5. On E13.5, decorin mRNA was expressed in the epithelia and mesenchyme on the nasal side of the developing secondary palate. During the period the palate shelves were fusing (E14.5), decorin mRNA was strongly expressed in the mesenchyme but its expression pattern was asymmetric; decorin mRNA expression area in the nasal side was broader than that in the oral side. The expression of decorin mRNA was hardly detected in the mesenchyme on either side of the medial edge epithelium. After fusion (E15.5), its expression converged to the mesenchyme just around the palatine bone. Biglycan mRNA was ubiquitously distributed throughout the palatal mesenchyme for the mid-gestation period. Its expression area became limited to the ossification area within the palate after the late gestation period. In the retinoic acid-treated mice, the area of the decorin gene expression expanded to the core region of the palate primordium where little signal was observed in control mice. On the other hand, biglycan in the retinoic acid-treated mice did not show remarkable change in its distribution patterns compared with that in the control mice. These findings suggest that decorin and biglycan play distinct roles in palatogenesis, and decorin was more actively involved in the process of secondary palate formation than biglycan. Up-regulation of decorin gene expression in the retinoic acid-treated mice might influence the pathogenesis of cleft palate.     

No Improvement of Adult Height in Non-growth Hormone (GH) Deficient Short Children with GH Treatment

It is still in doubt whether the standard-dose growth hormone (GH) used in Japan (0.5 IU/kg/week, 0.167 mg/kg/week) for growth hormone deficiency is effective for achieving significant adult height improvement in non-growth hormone deficient (non-GHD) short children. We compared the growth of GH-treated non-GHD short children with that of untreated short children to examine the effect of standard-dose GH treatment on non-GHD short children. GH treatment with recombinant human growth hormone (rhGH) was started before the age of 11 yr in 64 boys and 76 girls with non-GHD short stature registered at the Foundation for Growth Science who have now reached their adult height. In 119 untreated boys and 127 untreated girls whose height standard deviation score (SDS) was below –2 SD at the age of 6 yr, height growth was followed until 17 yr. Height SDS was significantly lower before GH treatment in the GH-treated group than at the age of 6 yr in the untreated group, in both sexes. Adult height and adult height SDS were significantly greater in the untreated group than in the GH-treated group, in both sexes, although the change in height SDS did not differ significantly. Height SDS was significantly lower before GH treatment in the GH-treated group than at the age of 6 yr in the untreated group, so 57 boys and 57 girls whose height SDS at the age of 6 yr in the untreated group closely matched the height SDS before GH treatment in the GH-treated group were chosen for comparison. Height SDS did not differ significantly between the GH-treated group before GH treatment and the untreated group at the age of 6 yr, nor were there differences between these subgroups in adult height, adult height SDS, or height SDS change, in either sex. The effect of GH treatment is reported to be dose-dependent and doses over 0.23 mg/kg/week are reported to be necessary to improve adult height in non-GHD short children. Currently, the GH dose is fixed at 0.175 mg/kg/week in Japan, and we expected to find, and indeed concluded, that ordinary GH treatment in Japanese, non-GHD short children does not improve adult height.     

The effect of beta-adrenergic blockade in dilated cardiomyopathy — a questionnaire study in Japan

The effect of beta-blockade in dilated cardiomyopathy was studied by a questionnaire survey. Thirty-three cases were monitored in whom metoprolol (22 patients, 35.9 ± 20.4 mg, mean ± SD), propranolol (four patients, 26.3 ± 7.5 mg), or other beta-blockers (seven patients) were administered. Four patients died, but no direct relationship was found between administration of beta-blocker and death. The NYHA functional class improved significantly. The mean heart rate decreased from 96/min to 77/min (P < 0.01).=" the=" mean=" cardiothoracic=" ratio=" decreased=" from=" 55.6%=" to=" 52.1%=">P < 0.01).=" the=" mean=" ejection=" fraction=" of=" the=" left=" ventricle=" measured=" by=" echocardiogram=" increased=" from=" 30.4%=" to=" 36.9%=">P < 0.01).=" exercise=" tolerance=" in=" the=" treadmill=" test=" improved=" significantly.=" there=" was=" no=" change=" in=" blood=" pressure,=" nor=" were=" there=" arrhythmias=" seen=" on=" holter=" electrocardiograms.=" in=" two=" patients,=" congestive=" heart=" failure=" deteriorated=" after=" administration=" of=" beta-blockers.=" it=" is=" concluded=" that=" beta-adrenergic=" blockade=" has=" a=" beneficial=" effect=" in=" most=" of=" the=" patients=" with=" dilated=">This work was supported in part by a research grant from the Ministry of Health and Welfare and by a grant-in-aid for scientific research on priority areas and for general scientific research from the Ministry of Education, Science, and Culture, Japan, and Kanazawa Research Fund.     

Trends in age and anthropometric data at start of growth hormone treatment for girls with Turner syndrome in Japan

The purpose of this study is to evaluate the trends in age and anthropometric data for girls with Turner syndrome (TS) at start of growth hormone (GH) treatment in Japan. The data for analysis were obtained from a retrospective cohort, the Foundation for Growth Science, Japan. We analyzed trends in starting age of GH treatment for girls with TS in Japan after dividing subjects (n=1,478) into three registration periods: 1991-1994, 1995-1999 and 2000-2004. We also assessed the ratio of the subpopulation of subjects under five years of age. As results, the mean age (standard deviation (SD)) at start of GH treatment was significantly different among the three groups (10.95 (3.63), 10.15 (3.39) and 8.78 (3.61), p<0.0001). The proportion of the subjects under five years of age increased significantly over time (5.11%, 7.11% and 16.85%, p<0.0001). Mean (SD) height SD scores were also significantly different (-3.41 (0.87), -3.26 (0.81) and -3.17 (0.79), p<0.0001). However, the proportions of the karyotype of 45,X were not significantly different among the three groups (p=0.25). We concluded that age and shortness at initiation of GH treatment had been improving over time. However, these favorable trends have not fully met the conditions recommended by international clinical guidelines for TS.     

A Rapid Enzyme Immunoassay for Measurement of HBK in Blood

Abstract

An enzyme immunoassay has been developed for the measurement of HBK (4-amino-2-hydroxybutylyldibekacin) a new semisynthetic aminoglycoside antibiotic. Antisera were raised in rabbits by immunization with HBK conjugated to bovine serum albumin (BSA). 3′-Eno-HBK conjugated to alkaline phosphatase (ALP) was used as an enzyme labeled antigen. The antibody-bound drug was separated from free using goat anti-rabbit IgG serum. The assay can be completed within one hr by co-incubating the first and the second antibody. The present immunoassay allows detection of 10 ng HBK per ml of serum, and is applicable for monitoring HBK level in blood. HBK concentrations in human sera were determined by the immunoassay during and after infusion and the levels were compared with those determined by high performance liquid chromatography (HPLC) and antimicrobial assay.     

The enhancing effect of a triethanolamine-ethanol-isopropyl myristate mixed system on the skin permeation of acidic drugs

The effect of a TEI enhancer mixed system consisting of triethanolamine (T), ethanol (E) and isopropyl myristate (IPM) on the skin permeation of acidic, basic and neutral drugs were evaluated in vitro using excised hairless rat skin. The binary enhancer system consisting of IPM and ethanol (El) produced marked improvement on the penetration of all the drugs tested. When T was added to the EI system, a greater enhancing effect was found only on acidic drugs with a carboxyl group, compared with the flux in the EI system. On addition of another amine to the EI system, instead of T, mefenamic acid (MA), which exhibited the highest enhancing effect of the model drugs, showed an approximately 14-180 times greater flux than when delivered by the EI system. On simultaneous application of isosorbide dinitrate (ISDN) with MA in the TEI system, the flux of MA increased on increasing the T concentration in the TEI system, while, the flux of ISDN, a neutral drug, was unaffected by the T concentration. Application of MA in the EI system after pretreatment of the TEI system showed that the residual amount of T in the skin plays an important role in the skin permeation of MA. Furthermore, at a fixed concentration of MA, the flux of MA increased on increasing the T concentration in the TEI system, while the flux of E remained unchanged. Finally, the infrared spectrum of MA with amine in the E solution indicated that the carboxyl group of MA was ionized. These results demonstrated that the formation of an ion pair between MA and T, but not the effect of T on the skin, may be responsible for the enhanced skin permeation of MA using the TEI system.     

High-dose growth hormone (GH) treatment in prepubertal GH-deficient children

Two clinical studies were conducted to determine the effect of different doses of growth hormone (GH) on prepubertal growth in GH-deficient boys. In one study, GH doses of 1.0 and 1.5 IU/kg/week (0.33 and 0.5 mg/kg/week) were given to groups of five children and compared with a conventional Japanese dose of 0.5 IU/kg/week (0.17 mg/kg/week) in 15 children. A significant dose-dependent increase in height velocity occurred in the first year of treatment, but differences between doses were not significant thereafter. In a second study, GH was administered to ten boys at a dose of 0.5 IU/kg/week for the first year, 0.75 IU/kg/week for the second year, 1.0 IU/kg/week for the third year and 0.5 IU/kg/week for the fourth and subsequent years (0.17, 0.25, 0.33 and 0.17 mg/kg/week, respectively). During the second and third years of GH treatment, these boys had significantly higher growth rates than controls, who were given GH at 0.5 IU/kg/week (0.17 mg/kg/week) throughout, indicating successful reduction in 'waning' of the treatment effect. At the end of the fourth year, the different protocols from the two studies had both resulted in a greater height SDS than the controls, and did not advance bone maturation. In conclusion, these protocols may be effective in increasing prepubertal height gain in children with GH deficiency.     

Short stature in a girl with partial monosomy of the pseudoautosomal region distal to DXYS15: further evidence for the assignment of the critical region for a pseudoautosomal growth gene(s)

This report describes a 12 year 10 month old girl with short stature and a non-mosaic 46,X,Xp+ karyotype. Her height remained below −2 SD of the mean, and her predicted adult height (143 cm) was below her target height (155·5 cm) and target range (147·5 cm−163·5 cm). Cytogenetic and molecular studies showed that the Xp+ chromosome was formed by an inverted duplication of the Xp21.3−Xp22.33 segment and was missing about 700 kb of DNA from the pseudoautosomal region distal to DXYS15. The results provide further support for the previously proposed hypothesis that the region between DXYS20 and DXYS15 is the critical region for a pseudoautosomal growth gene(s).     

Open-ended questions: are they really beneficial for gathering medical information from patients?

Open-ended questions, which allow patients to discuss their concerns freely, are widely considered an efficient method gathering medical information from patients during a medical interview. However, few studies have examined the relationship between the use of open-ended questions and the amount of information obtained from patients during the medical interview. This study examines this relationship using a relatively large sample size under more standardized conditions than in previous studies. The Japanese Group for Research on the Medical Interview undertook this research in 2002-2003. A total of 1,527 medical students conducted medical interviews with standardized patients, and 1,220 met the inclusion criteria for this study. The interview was limited to five minutes. Evaluators (medical school faculty physicians) evaluated the use of open-ended questions during the medical interview. The reliability of the evaluation sheet was also examined. The amount of information obtained was measured through the medical interview evaluation sheet. The use of open-ended questions was positively related to the amount of information elicited from the patients (F = 41.0, p < 0.0001). This study provides data to support the hypothesis regarding the favorable relationship between the use of the open-ended questions and the amount of information from the patients.