Positive relationship between urinary sodium chloride and blood pressure in Chinese health examinees and its association with calcium excretion.

The relationships between salt, urinary calcium and blood pressure were studied in 401 middle-aged Chinese men. Seven overnight urine samples were collected. Three consecutive blood pressure measurements were made on two occasions. The 24-h urinary sodium estimate was positively associated with both mean systolic and diastolic blood pressure (P less than 0.001), controlled for age and body mass index. Urinary chloride was also positively associated with blood pressure (P less than 0.001) at a magnitude similar to that of sodium. Potassium was not related to blood pressure. Urinary calcium was significantly correlated to sodium (r = 0.46) and was positively associated with systolic (P less than 0.001) and diastolic (P less than 0.01) blood pressure. The relationship between calcium and blood pressure was partly explained by salt intake. Similar findings were obtained using electrolyte to creatinine ratios. These results confirm the positive relationship between salt and blood pressure within a Chinese population living in Taipei and indicate a possible, positive relationship between blood pressure and urinary calcium excretion, either dependent or independent of salt intake.

Effects and dose--response relationships of skin cancer and blackfoot disease with arsenic.

In a limited area on the southwest coast of Taiwan, where artesian well water with a high concentration of arsenic has been used for more than 60 years, a high prevalence of chronic arsenicism has been observed in recent years. The total population of this "endemic" area is approximately 100,000. A general survey of 40,421 inhabitants and follow-up of 1,108 patients with blackfoot disease were made. Blackfoot disease, so-termed locally, is a peripheral vascular disorder resulting in gangrene of the extremities, especially the feet. The overall prevalence rates for skin cancer was 10.6 per 1000, and for blackfoot disease 8.9 per 1000. Generally speaking, the prevalence increased steadily with age in both diseases. The prevalence rates for skin cancer and blackfoot disease increased with the arsenic content of well water, i.e., the higher the arsenic content, the more patients with skin cancer and blackfoot disease. A dose-response relationship between blackfoot disease and the duration of water intake was also noted. Furthermore, the degree of permanent impairment of function in the patient was directly related to duration of intake of arsenical water and to duration of such intake at the time of onset. The most common cause of death in the patients with skin cancer and blackfoot disease was carcinoma of various sites. The 5-year survival rate after the onset of blackfoot disease was 76.3%; the 10-year survival rate was 63.3% and 15-year survival rate, 52.2%. The 50% survival point was 16 years after onset of the disease.

Molecular cloning and characterization of a human brain-specific gene implicated in neuronal differentiation.

A 2.5 kb human cDNA clone containing a CAG trinucleotide repeat, designated HB20, was isolated from a human fetal brain library. Northern analysis on multi-tissue blots and various cell lines confirmed that HB20 is specifically expressed in the brain. Its expression is low in two glioma cells, moderate in a neuron precursor cell, NT2, but absent in lymphoma, cervical carcinoma, or colonic carcinoma cells. Significant increase of HB20 mRNA was shown along with retinoic acid-induced terminal differentiation of NT2 cells into neuron cells, hNT. Homology comparison of the predicted HB20 amino acid sequence with the current database revealed that it belongs to a newly recognized protein family composed of nucleosome assembly proteins and SET proto-oncogene, which has been shown to interact specifically with B-type cyclins involved in the control of cell proliferation. Together with the detection of nuclear localization signals and apparent nuclear distribution of expressed protein, HB20 is likely to be a brain-specific nuclear protein, functioning in the process of neuronal differentiation.

Marrow donor registry and bone marrow transplantation from unrelated donors in Taiwan: initial experience of the Tzu Chi Taiwan Marrow Donor Registry (TCTMDR).

To evaluate the outcomes of unrelated bone marrow transplantation facilitated by TCTMDR, we focused on 48 marrow transplants performed in Taiwan during the period May 1994 to June 1997. Follow-up of these 48 cases was made up to 30 May 1998. The average length of follow-up was 328 days (range 7-1385 days). All the donor/recipient pairs were HLA-A, B and DR matched and were divided into two risk groups based on diagnosis and stage of disease. There were 24 standard risk and 24 high risk patients. Engraftment occurred in 40 patients (83.3%). Acute and chronic GVHD was observed in 80% of evaluable patients and accounts for 41% of deaths. The second leading cause of death was infection, accounting for 35% of deaths. The overall probability of survival for the 48 patients after BMT over 2 years was 33.3% (95% CI 19.67-46.32%). The probability of survival for standard risk and high risk groups was 54% and 8%, respectively. In multivariate analysis, patients who were younger, in the standard risk group, or with a shorter search interval showed a higher survival probability.

Prenatal and molecular diagnosis of beta-thalassemia major in Taiwan by naturally and amplified created restriction sites.

To characterize mutations rapidly in 43 patients with beta-thalassemia major in Taiwan, we utilized a method of natural and amplified created restriction site (ACRS) analysis for detection of beta-globin gene mutation. After analysis, eight different point mutations were found among 86 known chromosomes. IVS-2 nt 654 (C-->T), accounting for 40 of the 86 mutations with mutant beta-globin genes, is the most common mutation, followed by frameshift codons 41/42 (-TCTT) in 28 mutations, -28 mutation (A-->G) in 7 mutations, nonsense codon 17 (A-->T) in 5 mutations, frameshift codons 27/28 (insertion of C) in 2 mutations, IVS-1 nt 1 (G-->T) in 2 mutations, frameshift codons 71/72 (insertion of A) in 1 mutation, and IVS-1 3' end TAG-->GAG in 1 mutation. The first four mutations account for 80 of all 86 mutations of beta-thalassemia major in Taiwan. Furthermore, the beta-globin gene mutation was identified successfully in one chorionic villi biopsy for prenatal diagnosis and in specimen of blood from one patient who had received bone marrow transplantation (BMT). Complete diagnosis is possible in all of the Chinese families with beta-thalassemia in Taiwan, and the first trimester prenatal diagnosis can be achieved simply by using only 13 oligonucleotide primers and 10 restriction endonucleases. This non-radioactive assay was shown to be a rapid, sensitive, precise and safe method in detecting the mutations of beta-thalassemia in Taiwan.

Epidemiology of hypertension among Chinese in Taiwan.

A series of population surveys in Taiwan have found that hypertension was present in 14.1% in 1976 and in 14.8% in 1984 in those aged above 18, and in 33.4% in 1976 and in 31.4% in 1987 in the elderly. In 1976, 4.5% of hypertensives aged 18 and over had good blood pressure control and in 1982 this figure was still only 4.9%. The outcome among 3037 untreated hypertensives out of a general population of 17,000 in southern Taiwan showed that 49.9% of those hypertensives died in the 22-year follow-up period. The annual death rate from stroke was 5.9/1000/year in untreated hypertensives but only 0.8/1000/year in normotensives. Compliance rate for treatment of hypertension in Taiwan showed that 81.6% of patients had good compliance under a free-of-charge programme with 86.1% of them having their blood pressure under control. In a comparison of the efficacy of antihypertensive drugs as first-line, propranolol (40.8%) proved to be more efficacious than trichlormethiazide (33.2%) in Taiwanese hypertensives. The difference however was not statistically significant.

Prevalence of diabetes mellitus and impaired glucose tolerance in Aborigines and Chinese in eastern Taiwan.

The aim of this study was to determine the prevalence of diabetes mellitus and impaired glucose tolerance (IGT) in three different ethnic groups in eastern Taiwan. The study was performed among Han Chinese, aboriginal Ami and aboriginal Atayal in six rural villages. Inhabitants aged 40 years and over were invited to participate. A 75-g oral glucose tolerance test (OGTT) was used as suggested by the World Health Organization (WHO) for population screening purposes. WHO criteria were used for determining the results. A total of 1013 adults (460 men and 553 women) were examined with a response rate of 62.1%. There were no significant differences in sex, age and history of diabetes between responders and non-responders. The age-adjusted prevalence of diabetes was 11.0% (9.8% in men and 12.3% in women) in the Chinese, 9.1% (12.1% in men and 7.4% in women) in the Amis, 10.8% (11.5% in men and 9.4% in women) in the Atayal and 9.9% (11.5% in men and 8.5% in women) for the two aboriginal groups together. Although sex differences in prevalence of diabetes were not statistically significant, it seems that diabetes was slightly more prevalent in Chinese women than in Chinese men (12.3 versus 9.8%). Nonetheless, the prevalence rate of diabetes was somewhat higher in the aboriginal males than in the aboriginal females (12.1 versus 9.8% for Ami and 11.5 versus 10.7% for Atayal). The prevalence of IGT was 7.2, 8.5, 10.8 and 9.7% for the Chinese, Amis, Atayal and the two aboriginal groups, respectively. There were no substantial differences in the prevalence of diabetes and IGT among these three ethnic groups. Environment, rather than ethnicity, was more likely the predominant factor. It was found that the prevalence of diabetes in this study was about twice as high as that reported in a 1987 survey in Taiwan. The discrepancy may be due to different screening methods and assessment periods.

Blackfoot disease in Taiwan: a 30-year follow-up study.

Blackfoot disease is an endemic peripheral vascular disease found among the inhabitants of a limited area on the southwest coast of Taiwan, where artesian well water with a high concentration of arsenic has been used for more than eighty years. The natural history of blackfoot disease, based on a prospective study of 1,300 patients, is presented. The overall male/female ratio was 1.5:1. Although the clinical onset was usually insidious, it may be quite sudden and almost always begins with numbness or coldness in one or more extremities, usually the feet. Ultimately, rest pain develops and progresses to gangrene. In this series, 68% of the patients underwent spontaneous or operative amputation, and the reamputation rate was 23.3%. Lower extremity involvement in blackfoot disease was observed in 97.7% of the cases. The average annual rate for major amputation was 3.81 per 100 patient-years. The factors influencing the prognosis, such as amputation in relation to age and disease onset, are analyzed. The case fatality rate was 66.5% during thirty years; 44% of these were cardiovascular deaths. The annual death rate was 4.84 per 100 patient-years. Other reported case fatality rates for vascular insufficiency are reviewed. A dose-response relationship between blackfoot disease and the duration of water intake was also noted. The survival rates after the onset of blackfoot disease were: five years, 76.0%; ten years, 59.5%; twenty years, 38.2%; thirty years, 28.6%. The 50% survival point was 13.5 years after onset of the disease.

Risk factors associated with coronary artery stenosis among patients with chest pain in eastern Taiwan.

To analyze the risk factors for coronary artery stenosis among patients who were admitted to the hospital with chest pain in eastern Taiwan, we retrospectively reviewed the clinical data of 444 patients who received coronary arteriography, including 62 aborigines. Results indicated that there were 268 patients (64%) with coronary stenosis. Male to female ratio, mean age, pack-years of cigarette smoking, and hypertension were significantly higher in patients with coronary stenosis (CS group) than in patients without coronary stenosis (control group). There were also significant differences in the serum levels of total cholesterol, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol between the CS and control groups. The total cholesterol and low-density lipoprotein cholesterol of both the CS and control groups were lower than those reported in western Taiwan. The prevalence of coronary stenosis among Taiwanese patients who presented with chest pain was significantly higher than in aborigines (64% vs 38%), although there were no significant differences in common risk factors between these two ethnic groups. These results revealed that the common risk factors in eastern Taiwan were the same as those reported here and suggest that race may be an important risk factor for coronary stenosis.

Ambulatory blood pressure in normal Chinese.

Noninvasive ambulatory blood pressure monitoring (NABPM) has been playing an increasing role in the diagnosis of hypertension and in the evaluation of antihypertensive drugs. NABPM data for the normal Chinese population has not yet been established. However, data obtained from 25 young male Chinese adults has been analysed. Average ambulatory blood pressure was 120 +/- 8/74 +/- 7 mmHg for the whole-day monitoring. There was an evident diurnal change of blood pressure during the 24-hour monitoring period with higher blood pressure levels being recorded during the daytime, rather than during the nighttime (7.8 +/- 9.7/4.4 +/- 4.8 mmHg; p less than 0.001). Maximal hourly blood pressure averages occurred during the late morning, while minimal hourly blood pressure averages occurred around midnight. The variability in blood pressure was 11 +/- 3/9 +/- 2 mmHg for the daytime and 11 +/- 3/8 +/- 2 mmHg for the nighttime. The incidence of abnormally high blood pressure ranged widely. Eating would raise both the systolic and diastolic blood pressure, while sleep caused a significant fall in blood pressure. This study offers basic data for the study of NABPM in young normotensive Chinese adults.

Outcome among untreated hypertensives in the general population in Taiwan.

The outcome of untreated hypertension was investigated in a population of 17,713 persons in southern Taiwan who were aged 15 or over when they had taken part in a blood pressure survey in 1963. In the 27-year follow-up period, 55.8% of the overall mortality was comprised of those who were found to be hypertensive (as defined by WHO) in 1963, 31.3% by borderline hypertensives, and 22.6% by normotensives. The 27-year mortality rate due to stroke was much higher in hypertensives than in normotensives (11.4% vs 1.8%, respectively). The 5-year survival rates for mild, moderate and severe hypertensives were 89.9%, 82.7% and 72.3%, respectively, and the 20-year rates were 60.2%, 37.2% and 25.2%, respectively. The causes of death were also recorded: among hypertensives, stroke accounted for 23.2% of all deaths of known cause, cancer 20.5%, cardiovascular disease 21.7%, respiratory disease 11.8%, and other causes 22.9%. From the results, it is concluded that obvious differences in mortality and cause of death exist between untreated hypertensives and normotensives.

Two distinct upstream regulatory domains containing multicopy cellular transcription factor binding sites provide basal repression and inducible enhancer characteristics to the immediate-early IES (US3) promoter from human cytomegalovirus.

The US3 gene of human cytomegalovirus (HCMV) is expressed at immediate-early (IE) times in permissive HF cells, but not in nonpermissive rodent cells, and encodes several proteins that have been reported to have regulatory characteristics, although they are dispensable for growth in cell culture. Both spliced and unspliced forms of US3 IE transcripts are associated with the second of only two known large and complex upstream enhancer domains within the 229-kb HCMV genome, which we refer to as the IES cis-acting control region. Only the 260-bp proximal segment (from -313 to -55) of the 600-bp IES control domain, which contains multicopy NF-kappaB binding sites, proved to be necessary to transfer both high basal expression plus phorbol ester- and okadaic acid-inducible characteristics to heterologous promoters in transient assays in U-937 and K-562 cells. However, the IES control region contains a distinctive 280-bp distal domain, characterized by the presence of seven interspersed repeats of a 10-bp TGTCGCGACA palindromic consensus motif that encompasses a NruI site. This far upstream Nru repeat region (from -596 to -314) imparted up to 20-fold down-regulation effects onto strong basal heterologous promoters as well as onto the IES enhancer plus minimal promoter region in both U-937 and K-562 cells. Functional Nru repressor elements (NREs) could not be generated by multimerizing either the palindromic (P) Nru motifs alone or adjacent degenerate interrupted (I Nru motifs alone. However, multimerized forms of the combined P plus I elements reconstituted the full 20-fold cis-acting down-regulation phenotype of the intact NRE domain. The P and I forms of the Nru elements each bound independently and specifically to related cellular DNA-binding factors to form differently migrating A or B complexes, respectively, whereas the combined P plus I elements bound cooperatively to both the A and B complexes with high affinity. Interestingly, nuclear extracts from U-937, K-562, HeLa, and Vero cells all formed both the A and B NRE binding factor complexes, whereas those from HF cells produced only A complexes, and Raji, HL60, and BALB/c 3T3 cells lacked both types of binding factor complexes. The core pentameric CGACA and CGATA half sites present in both the P and I Nru motifs are related to recently described Drosophila chromosomal insulator binding sites. Therefore, in addition to its cis-repression or silencer characteristics, the NRE domain appears likely to act to shield adjacent segments of the viral genome from the chromatin-reorganizing effects of the IES-inducible enhancer. We speculate that differential expression and regulation of the IES enhancer-controlled US3 protein, either in concert with or separately from the major IE (MIE) enhancer-controlled IE1 and IE2 transactivator proteins, may play a critical role in determining HCMV permissiveness in some cell types and perhaps also in the establishment of or reactivation from latency.

Klebsiella pneumoniae-induced mycotic aneurysm of the abdominal aorta complicated by bloody pleural effusion--a case report.

A 68-year-old diabetic male who suffered from recurrent severe lumbago and high fever was found to have mycotic abdominal aneurysm. His symptoms did not improve after maximum-dose antibiotic therapy. Bloody pleural effusion on the left side was noticed hours before he expired. Klebsiella pneumoniae alone was isolated from blood from cellulitis-related bacteremia, when aneurysm formation was complete and later from bloody pleural effusion. To our knowledge, this is the first report of mycotic abdominal aneurysm of solely Klebsiella pneumoniae complicated by bloody pleural effusion.

[Locomotion of dystrophin-deficient mice].

The purpose of our study was to make a comparison of the motor function between murine dystrophy mice (MDX mice) and C57BL/10ScSn control mice. The locomotor activities of mice were measured by an animal three-dimension optical monitor. Measurements were performed at ages of 21, 45 and 60 days. Animals were tested in a dark and peaceful environment under room temperature (25 degrees C-27 degrees C) at night for an hour. Results showed that the most important differences were in data on vertical activities. Among 15 variables of locomotor activity detected by the optical activity monitor, the MDX mice and control mice at age 21 days showed significant differences in 12 variables. However, the MDX mice and control mice at age 45 days revealed significant differences in only 7 variables. The MDX mice and control mice at age 60 days had significant differences for only one variable. The results may be explained by the fact that dystrophin-deficient mice undergo more severe dystrophic degeneration at an early age (5 weeks) and new regeneration of their muscle fibres is prevalent. Moreover, a functional recovery occurred in MDX skeletal muscle which was probably due to the regeneration of dystrophic muscle.

Molecular basis and hematological characterization of Hb H disease in southeast Asia.

We molecularly characterized sixty-seven cases of Hb H disease by the polymerase chain reaction. The strategy depends on amplifying the alpha-thalassemia-1 (alpha-thal-1) gene by primers flanking the breakpoint and sequence differences of the 3' end of the alpha-globin gene and the nonhomologous elements I, II, and III among different types of alpha-thala-2. In the 67 cases studied, all involved alpha-thal-1 of the Southeast Asia type (SEA) in combination with deletional or nondeletional alpha-thal-2. Thirty-two cases were of the deletion form and 35 cases were of the nondeletion form. In 32 cases of the deletion form, 29 cases were rightward deletion (-alpha 3.7), and three cases were leftward deletion (-alpha 4.2). We found that all of the nondeletion forms were alpha-thal-1 of SEA type with Hb CS. After the subtyping of Hb H with -alpha 3.7, 26 out of 29 were type I deletion and 3 out of 29 were type II deletion. Comparisons of clinical data of deletion forms and the nondeletion form showed that there were earlier occurrence of anemic symptoms and a larger erythrocyte volume in the nondeletion form group (P < 0.005).