Iron is fastidiously utilized by living cells, since it is an essential element, but is toxic in excess. Cells take up iron via a transferrin-transferrin receptor-dependent endocytotic process. The iron thus taken up is used for essential biological functions including oxygen transport, electron transfer, and DNA synthesis. The intracellular level of iron is tightly controlled, through regulation of the cellular uptake of iron and the sequestering of low molecular labile iron into the storage protein ferritin. The known proteins of iron transport and storage, transferrin, transferrin receptor and ferritin, have been recently linked with a number of newly identified proteins that are responsible for inherited diseases of iron metabolisms and play critical roles in the maintenance of iron homeostasis. These proteins are involved in regulation of intracellular levels of iron, iron transport, and heme transport and the oxygen-dependent regulation of gene expression. On the other hand, most iron is transported into mitochondria and immediately used for the biosynthesis of heme in erythroid cells. The heme biosynthesis in mitochondria is coupled with the supply of iron, and the heme, exported from mitochondria, is utilized as prosthetic groups of hemeproteins. Furthermore, non-erythroid and erythroid cells possess the different regulatory systems for the biosynthesis of heme; iron positively regulates the biosynthesis in erythroid cells while heme negatively regulates it in non-erythroid cells. Because of the toxicity and insolubility of heme, the intracellular level of uncommitted heme is maintained at a low concentration (< 10−9 M). The influx and efflux of heme also help to prevent cytotoxicity. Finally, heme-binding transcriptional factors such as Bach1 and NPAS2 regulate the transcription of several genes involved in the synthesis and degradation of heme-hemeproteins. The discovery of new molecules related to disorders of iron and heme metabolism is ascribable to a complete mechanistic understanding of the cellular network of iron homeostasis. The network of interactions that link iron and heme metabolisms with functions of cellular regulation involving oxidative stress and inflammations contributes to new insights into clinical aspects of disorders.
It has been known for many years that deformations of the occlusal plane of the teeth cause indefinite symptoms such as headaches or stiffness of the shoulders. However, how the occlusal plane of the teeth should be corrected remains uncertain. The purpose of this study was to examine whether a correction of the deviation of the maxillary occlusal plane (MOP) from the center of dens of axis vertebrae (DAV) improves symptoms in patients having intractable headache or shoulder-stiffness. Forty patients who complained of dental abnormalities and persistent headache or shoulder-stiffness that had not responded to conventional medical treatment and 17 healthy controls were recruited. All subjects received a lateral cephalometric x-ray examination to measure a distance from the MOP and the center of DAV. In the healthy subjects, both the upper and the lower shift of the MOP from the center of DAV were minimal (the upper shift was 1 ± 2 [mean ± S.D.] mm and the lower shift was 4 ± 4 mm). By contrast, the patients had a significantly greater deviation of the MOP from the center of DAV. Dental adjustment treatment was performed in fourteen patients who had a substantial deviation of the MOP from the center of DAV. Those patients were asked about their symptoms which were scored using a point system and were compared before and after treatment. An adjustment procedure of the MOP passing through the DAV significantly relieved clinical symptoms in these patients (before 42.5 ± 34.4 vs after 7.0 ± 8.2, p < 0.01). Correction of the MOP passing through the near center of DAV might be effective in relieving clinical symptoms associated with dental deformities.
We compared clinical features and vascular complications of patients with diabetes mellitus associated with liver cirrhosis versus patients with type 2 diabetes mellitus. Subjects were 19 patients (LC-DM group) in whom diabetes was diagnosed after development of liver cirrhosis. Control consisted of 38 patients with type 2 diabetes (T2DM group) matched for sex, age, duration of diabetes, body mass index, treatment, and degree of glycemic control, which was determined by glycoalbumin. The LC-DM group had significantly more smokers, higher serum insulin levels, more insulin resistance calculated by homeostasis model assessment, lower blood counts (white and red blood cells, hemoglobin, and platelets), and lower serum levels of total cholesterol, triglyceride, low density lipoprotein cholesterol and lipoprotein (Lp)(a) than the T2DM group. The incidence of diabetic retinopathy and cerebrovascular disease was significantly lower in the LC-DM group compared to the T2DM group. Logistic regression analysis indicated that Lp(a) and the diabetes duration were significant predictors for the retinopathy, while Lp(a) was a significant predictor for the cerebrovascular complication. In diabetes associated with liver cirrhosis, the incidence of diabetic retinopathy and cerebrovascular disease is lower than in type 2 diabetes mellitus in this study, probably because of lower levels of serum Lp(a).
Ornithine aminotransferase (OAT) deficiency (MIM: 258870) is a rare congenital metabolic disorder characterized by gyrate atrophy of the choroid and retina. Here, we report a 37-year-old male with gyrate atrophy of the choroid and retina who has been treated for 18 years. At the age of 7 years, the patient consulted an ophthalmologist due to progressive loss of vision. A large atrophied area was observed in his retina, and OAT deficiency was suspected. At the age of 19 years, amino acid analysis revealed high serum ornithine levels (1,140 nmol/ml), with the normal range being 40-100 nmol/ml. He was treated with vitamin B6 300 mg/day for 6 months, which successfully reduced his serum ornithine levels by 20-30%. For 18 years since, his serum ornithine levels have been maintained with vitamin B6 medication. There was no further impairment of vision or increase in the atrophied area, as judged by ophthalmoscopic examination. OAT activity was undetected in white blood cells of the patient and was 105% and 45% of normal values in his wife and son, respectively. OAT gene analysis revealed a novel mutation of Gly237Asp in exon 7 (710G > A) in both alleles of the patient, while his son was a heterozygote for the mutation. Notably, this novel mutation is associated with a vitamin B6-responsive phenotype. Therefore, early diagnosis and treatment with vitamin B6 may prevent loss of vision in some patients with OAT deficiency.
Use of high-density barium (= or > 180 w/v%) has been widely spread in community-based mass screening for gastric cancer in Japan. However, the impact on outcomes of the screening has not been fully evaluated. Then, we investigated the advantage of high-density barium use by comparing the outcomes between a period with high-density barium and that with low-density barium (< 180 w/v%) each for 3 consecutive years between 1991and 2002 at 5 medical examination organizations in Niigata Prefecture, Japan. Multivariate logistic regression analysis adjusted for age, sex and medical organization revealed that the introduction of high-density barium decreases the positive finding rate in initial mass screening x-ray examinations by 12% (odds ratio, 0.88; 95% confidence interval, 0.86 - 0.90) and increase the gastric cancer detection rate by diagnostic examination by 15% (odds ratio, 1.15; 95% confidence interval, 1.01-1.31). We conclude that introduction of high-density barium has improved the efficiency of mass screening for gastric cancer by decreasing unnecessary diagnostic examinations and reducing the total personal and public health costs. Thus, nationwide use of high-density barium is recommended for mass gastric cancer screening in Japan.
Cardiovascular disease (CVD) is the major cause of death in patients with type 2 diabetes mellitus. However, the diagnosis of CVD is delayed due to concealment of antecedent symptoms by factors such as autonomic neuropathy. In this study, we aimed to investigate the frequency of silent ischemia by using exercise electrocardiogram (ECG). The present study included 500 Turkish patients with type 2 diabetes (male/female: 222/278), who showed no evidence of CAD and angina pectoris or no sign(s) of ischemic changes in resting ECGs. All patients underwent treadmill exercise test according to Bruce protocol, and 62 cases (12.4%) exhibited abnormal changes. These patients identified by exercise ECG consisted of 28 males (28/222, [12.6%]) and 34 females (34/278, [12.2%]) and were then examined by coronary angiography. CAD was diagnosed in 53 individuals by coronary angiography. The abnormalities of exercise test are associated with the age of the patients or the duration of diabetes (p < 0.05). There is no significant difference in the severity of coronary disease or in the prevalence of silent ischemia between male and female patients. However, among the patients identified by exercise ECG females have higher body mass index than males, suggesting that obesity may represent the risk factor of CAD in women with type 2 diabetes.
It is necessary and important to quantify the handicap sustained by individuals with spinal cord injury (SCI); however, few instruments are available to measure the level of the disability. One of the best developed and most often used measures is the Craig Handicap Assessment and Reporting Technique (CHART). Nevertheless, a Japanese version has not yet been developed and tested for SCI individuals. The purpose of this study was to develop a Japanese version of the CHART (CHART-J) and to investigate its test-retest reliability and discriminant validity in SCI in Japan. Fifty-four individuals with SCI participated in the test-retest reliability study and 293 participated in the discriminant validity analysis. We have shown that the test-retest reliability coefficients of the CHART-J range from 0.57 to 1.00. In addition, its discriminant validity is acceptable for individuals with SCI in Japan. Therefore, the CHART-J is useful as a measure of disability for Japanese individuals with SCI.
In this study we have reported a 12-year old girl patient who visited out-patient clinic with the history of headache and convulsion. The patient was diagnosed as miliary tuberculosis and multiple brain tuberculomas. Miliary infiltration was observed in chest x-ray and high-resolution thorax computed tomography (CT), and multiple tuberculomas surrounded with wide edema was observed in Magnetic Resonance Imaging (MRI). Acid-fast bacilli were detected in inducted sputum and gastric fluid. Focal epileptiform activity was seen in electroencephalography (EEG). The patient was administered antitubercular, anti-edema and antiepileptic therapy. The patient had not experienced convulsion for the second time and EEG had been normal; therefore her treatment was completed within 12 months. Chest x-ray and high-resolution thorax CT findings turned to normal and brain MRI findings improved significantly. As a conclusion, tuberculosis disease has very different clinical pattern depending on the organs it involves. The significance of our case is due to the presence of both the miliary tuberculosis and intracranial tuberculomas. The patient was admitted to the hospital due to central nervous system symtoms rather than pulmonary symptoms.