The timed "up & go" test is a useful predictor of falls in community-dwelling older people.
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Biomedical subjects
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The polyhydroxyalkanoate (PHA) synthase gene of Comamonas acidovorans DS-17 (phaCCa) was cloned by using the synthase gene of Alcaligenes eutrophus as a heterologous hybridization probe. Complete sequencing of a 4.0-kbp SmaI-HindIII (SH40) subfragment revealed the presence of a 1,893-bp PHA synthase coding region which was followed by a 1,182-bp beta-ketothiolase gene (phaACa). Both the translated products of these genes showed significant identity, 51.1 and 74.2%, respectively, to the primary structures of the products of the corresponding genes in A. eutrophus. The arrangement of PHA biosynthesis genes in C. acidovorans was also similar to that in A. eutrophus except that the third gene, phaB, coding for acetoacetyl-coenzyme A reductase, was not found in the region downstream of phaACa. The cloned fragment complemented a PHA-negative mutant of A. eutrophus, PHB-4, resulting in poly-3-hydroxybutyrate accumulation of up to 73% of the dry cell weight when fructose was the carbon source. The heterologous expression enabled the incorporation of 4-hydroxybutyrate (4HB) and 3-hydroxyvalerate monomers. The PHA synthase of C. acidovorans does not appear to show any preference for 4-hydroxybutyryl-coenzyme A as a substrate. This leads to the suggestion that in C. acidovorans, it is the metabolic pathway, and not the specificity of the organism's PHA synthase, that drives the incorporation of 4HB monomers, resulting in the efficient accumulation of PHA with a high 4HB content.
Two types of polyhydroxyalkanoate (PHA) biosynthesis gene loci (phb and pha) of Pseudomonas sp. strain 61-3, which produces a blend of poly(3-hydroxybutyrate) [P(3HB)] homopolymer and a random copolymer (poly(3-hydroxybutyrate-co-3-hydroxyalkanoate) [P(3HB-co-3HA]) consisting of 3HA units of 4 to 12 carbon atoms, were cloned and analyzed at the molecular level. In the phb locus, three open reading frames encoding polyhydroxybutyrate (PHB) synthase (PhbCPs), beta-ketothiolase (PhbAPs), and NADPH-dependent acetoacetyl coenzyme A reductase (PhbBPs) were found. The genetic organization showed a putative promoter region, followed by phbBPs-phbAPs-phbCPs. Upstream from phbBPs was found the phbRPs gene, which exhibits significant similarity to members of the AraC/XylS family of transcriptional activators. The phbRPs gene was found to be transcribed in the opposite direction from the three structural genes. Cloning of phbRPs in a relatively high-copy vector in Pseudomonas sp. strain 61-3 elevated the levels of beta-galactosidase activity from a transcriptional phb promoter-lacZ fusion and also enhanced the 3HB fraction in the polyesters synthesized by this strain, suggesting that PhbRPs is a positive regulatory protein controlling the transcription of phbBACPs in this bacterium. In the pha locus, two genes encoding PHA synthases (PhaC1Ps and PhaC2Ps) were flanked by a PHA depolymerase gene (phaZPs), and two adjacent open reading frames (ORF1 and phaDPs), and the gene order was ORF1, phaC1Ps, phaZPs, phaC2Ps, and phaDPs. Heterologous expression of the cloned fragments in PHA-negative mutants of Pseudomonas putida and Ralstonia eutropha revealed that PHB synthase and two PHA synthases of Pseudomonas sp. strain 61-3 were specific for short chain length and both short and medium chain length 3HA units, respectively.
Complementation analysis of a polyhydroxyalkanoate (PHA)-negative mutant of Aeromonas caviae proved that ORF3 in the pha locus (a 402-bp gene located downstream of the PHA synthase gene) participates in PHA biosynthesis on alkanoic acids, and the ORF3 gene is here referred to as phaJ(Ac). Escherichia coli BL21(DE3) carrying phaJ(Ac). under the control of the T7 promoter overexpressed enoyl coenzyme A (enoyl-CoA) hydratase, which was purified by one-step anion-exchange chromatography. The N-terminal amino acid sequence of the purified hydratase corresponded to the amino acid sequence deduced from the nucleotide sequence of phaJ(Ac) except for the initial Met residue. The enoyl-CoA hydratase encoded by phaJ(Ac) exhibited (R)-specific hydration activity toward trans-2-enoyl-CoA with four to six carbon atoms. These results have demonstrated that (R)-specific hydration of 2-enoyl-CoA catalyzed by the translated product of phaJ(Ac) is a channeling pathway for supplying (R)-3-hydroxyacyl-CoA monomer units from fatty acid beta-oxidation to poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) biosynthesis in A. caviae.
The involvement of moesin in measles virus (MV) entry was investigated with moesin-positive and -negative mouse embryonic stem (ES) cells. MV infection of these cells was very ineffective and was independent of moesin expression. Furthermore, when these cells were transfected to express human CD46, a 100-fold increase in syncytium formation was observed with these cells and was independent of the expression of moesin. The only obvious difference between moesin-positive and -negative ES cells was the shape of the syncytia formed. Moesin-negative ES cells expressing or not expressing human CD46 formed separate pieces of fragmented syncytia which were torn apart during spreading, whereas ES cells expressing moesin exhibited typical syncytia. In addition, moesin was not detected on the surface of any murine cells or cell lines that we have tested by a flow cytometric assay with moesin-specific antibodies. These findings indicate that murine moesin is neither a receptor nor a CD46 coreceptor for MV entry into mouse ES cells. Moesin is involved in actin filament-plasma membrane interactions as a cross-linker, and it affects only the spreading and shape of MV-mediated syncytia.
The differentiating cavernous body (CB) of postnatal rabbit penises was examined with a special reference to immunolocalizations for fibronectin (FN) and endothelin-1 (ET-1). At postnatal day 1, the CBs were embedded by an abundance of mesenchymal cells (MCs), and some of them were closely associated with endothelial cells of preexisting capillaries. Our electron micrographs indicated that such MCs are successively incorporated into the capillary endothelium as vasoformative cells. At this period, vascular sprouts of the helicine artery (HA), which were associated with the MCs, arose from the deep penile artery, and the transformation of such cells to endothelial and medial muscle ones was also indicated, and some MCs appeared to differentiate to epithelioid cells in the media. Immunoreactions for FN were preferentially localized in the rough endoplasmic reticulum (rER) and along the plasma membrane of such vasoformative MCs, and on the extracellular matrix components which connect these MCs with sprouts of both growing capillaries and HA. These findings suggest that FN, which is produced in the rER of the MCs, plays a crucial role in the mechanical linkage during the incorporation of vasoformative MCs into these penile vessels. Immunoreactions for ET-1 were preferentially localized on Weibel-Palade bodies in endothelial cells of the HA, implying the involvement of this peptide in the regulation of the local blood flow in this vessel.
The sinusoid organization during the development of fetal rat livers was studied using a SE-1 antibody, which we have previously established as a specific monoclonal antibody against rat sinusoidal endothelial cell (SEC). Expression and localization of the SE-1 antigen in the liver tissues of 13- to 21-day-old fetuses were immunofluorescently and immunoelectron microscopically examined. The first positive fluorescence was observed in the immature liver of 15-day-old fetuses. The initial positive staining was randomly distributed in the liver parenchyma and showed no direct relation to the large vessels which may be derived from the fetal vitelline veins. The positive linear staining increased in number and connected with each other during the course of development. The SE-1 staining pattern and the sinusoidal arrangement became similar to those of the adult liver after 20th day of gestation. Immunoelectron microscopically, the immature SEC showed a weak positive reaction for the SE-1 antigen at their membrane and was observed together with immature hepatocytes and hematopoietic cells in the 15-day-old fetal liver. Along with the liver development, SEC formed a sinusoid structure closely associated with hepatocytes and came to strongly express the SE-1 antigen. These results indicate that the organization of the hepatic sinusoid may start at around 15th day of the gestation and occurs randomly in the fetal liver parenchyma. It is also suggested that the expression of SE-1 antigen is possibly regulated by the intimate association with hepatocytes.
To detect a significant narrowing of the left anterior descending artery in patients with inferior/posterior myocardial infarction, 200 patients underwent standard exercise testing. Age, gender, and grade of stenosis of the left anterior descending artery were similar in 138 patients with inferior myocardial infarction and 62 with posterior myocardial infarction. In patients with left anterior descending artery stenosis, there were more lateral leads with ST-segment depression (1.8+/-1.0 vs 1.1+/-1.1; p<0.01) and fewer anterior leads with ST-segment depression (2.1+/-1.4 vs 2.9+/-1.4; p=0.02) in those with inferior myocardial infarction than in those with posterior myocardial infarction. Applying the criterion of exercise-induced ST-segment depression > or = 0.1 mV, sensitivities and specificities in detecting left anterior descending artery stenosis were 98% and 21% respectively in inferior myocardial infarction and 94% and 26% respectively in posterior myocardial infarction. In contrast, discriminant analysis revealed sensitivities and specificities of 77% and 91% respectively in inferior myocardial infarction and 71% and 81% respectively in posterior myocardial infarction using the variables related to severity of inducible ischemia and lateral and anterior lead ST-segment depression. These results indicate that a multivariate approach underscoring the site of myocardial infarction can help in identifying stenosis of the left anterior descending artery in patients with inferior/posterior myocardial infarction.
T-593 consists of two optical isomers, (-)-S and (+)-R. Our previous report showed that T-593 has biphasic effects, that is a long-lasting antisecretory action and an improving effect on gastric mucosal blood flow (GMBF). In this study, we compared the sole potency of each isomer on these bi-phasic effects. On the anti-secretory action investigated by the pylorus-ligation method, the (-)-S-isomer showed strong inhibition, while the (+)-R-isomer showed no effect, whereas the GMBF improvement was provided by the (+)-R-isomer. These results show the bi-phasic effects of racemic T-593 are separately derived from each isomer. The (-)-S-isomer strongly inhibited acute gastric mucosal lesion formation, with a potency comparable to T-593 itself, while the (+)-R-isomer showed less effect. Chronic gastric ulcer induced by acetic acid was, however, not healed by the sole treatment of each optical isomer, while racemic T-593 showed a significant effect. This result shows not only anti-secretion but also GMBF improvement is necessary to heal the chronic ulcer. This interesting property of T-593 is expected to raise the quality of ulcer healing (QOUH) and also may prevent ulcer recurrence.
We investigated the influence of T-593, a novel anti-ulcer agent, on the recurrence and relapse of cryocautery-induced gastric ulcer in rats, in comparison with the action of famotidine and ranitidine. The drugs were administered from the 7th to the 119th day and then discontinued to the 190th day after induction of gastric ulcer. The healing, recurrence and relapse process of gastric ulcer was sequentially observed with an endoscope. In the control group, the reduction of ulcer index was observed until the 76th day after ulcer induction followed by aggravation, suggesting the recurrence and relapse occurred on cryocautery-induced gastric ulcer in rats. In the famotidine and ranitidine groups, the recurrence and relapse occurred after cessation of administration. The recurrence and/or relapse rate of T-593 was lower than those of other drugs. In the histological measurement, the grades of heterotopic regenerated gland and inflammatory cell infiltration of T-593 was lower than those of the control and other drugs in the ulcer area. From these results, it is concluded that T-593 induces ulcer healing with a lower recurrence and/or relapse rate of ulcers than other conventional H2-antagonists, and T-593 may thus be a useful anti-ulcer drug for clinical therapy.
To examine the clinical implications of post-stroke hypertension, defined as the rise in blood pressure on admission after the onset of ischemic stroke as compared with the blood pressure before stroke, and to assess the relationship between the value of post-stroke hypertension and neurologic recovery, we retrospectively studied 28 patients admitted to the hospital within 24 h (mean+/-SD, 6.7+/-7.0 h) after a first-ever, acute non-embolic ischemic stroke, whose blood pressure had been recorded at the outpatient clinic within 3 mo before stroke. The Canadian Neurological Scale was used to assess stroke severity, and neurologic recovery during the acute phase was calculated. The average duration of hospitalization was 18+/-9 d. The value of post-stroke hypertension and stroke severity on admission independently and significantly correlated with neurologic recovery (odds ratio, 1.06; 95% confidence interval, 1.00-1.12 and odd ratio, 0.20; 95% confidence interval, 0.06-0.72, respectively). There was also a significant linear correlation between the value of post-stroke hypertension and neurologic recovery (r= 0.50, p< 0.01). Furthermore, blood pressure after the onset of ischemic stroke was quite independent of blood pressure before stroke. We conclude that the value of post-stroke hypertension correlates with neurologic recovery in patients with acute non-embolic ischemic stroke. These results suggest that blood pressure control mechanisms change after the onset of acute ischemic stroke.
This study is based on the dissections of 645 pelvic halves of Japanese cadavers. The branching of the internal iliac artery was classified according to Adachi's classification (1928), and the data was compared with previous reports. Type I was predominant in this, as well as, in previous studies. During the course of the present study, some branching forms were different from the types in Adachi's classification. Therefore, this classification was modified into 5 types and 19 groups. Type I-Group 1 was most frequently observed in the modified Adachi's classification, however, the frequency was less than 50% (46.8%). To clarify the basic branching pattern of the original internal iliac artery and to simplify the classification for medical purposes, a new classification system was designed. The superior gluteal, inferior gluteal and internal pudendal arteries were defined as the major branches of the internal iliac artery, and the umbilical artery was excluded from this group. The branching of the internal iliac artery was classified into 4 groups. Almost 80% of the present specimens were included in Group A of the new classification, namely, the internal iliac artery dividing into two major branches, the superior gluteal artery and the common trunk of the inferior gluteal and internal pudendal arteries. This type of branching seemed to be the basic branching pattern for the original internal iliac artery.
To evaluate the relation between blood pressure and diastolic function in the elderly, 28 apparently healthy volunteers underwent blood pressure measurements, echocardiographic examinations, and radionuclide angiography acquired in list mode. Casual blood pressure did not correlate with diastolic indices measured either by echocardiography or by a radionuclide method, except for peak filling rate during atrial contraction assessed by radionuclide angiography (r = 0.39, p < 0.05). Ambulatory blood pressure monitoring revealed significant correlations between peak filling rate during atrial contraction assessed by radionuclide angiography and blood pressure measured over 24 hours, while awake and during sleep. The time to peak filling rate and the velocity of early diastolic filling were found to correlate with blood pressure, but the best correlation was between blood pressure during sleep and peak filling rate during atrial contraction (r = 0.53, p < 0.005). These results show a direct relation between blood pressure and diastolic function in the elderly, which is stronger during sleep than during wakefulness.
To assess the clinical significance of silent myocardial ischemia (SMI) in the elderly, 113 patients with stable angina who showed ischemic ST depression during treadmill stress testing were studied by dipyrimadole thallium imaging and coronary arteriography. They were divided into two groups: 44 patients with silent ST depressions and 69 patients with painful ST depressions. The groups were compared for scintigraphic and coronary arteriographic features as well as prognosis. There was a significantly greater proportion of older patients (> or = 65 years) in the group with SMI (64%) than in the group with painful ischemia (38%) (p < 0.01), although there was no difference in the mean ages of the two groups. The prevalence of multivessel coronary stenosis was not significantly different between the two groups (45% in the SMI group and 61% in the group with painful ischemia). Treadmill stress testing showed no differences in exercise duration, maximal heart rate, maximal systolic blood pressure, or maximal ST depression between the two groups. Dipyrimadamole thallium imaging revealed similar results in the site of reversible defects (RD), i.e. 76% in the anterior area and 24% in the inferior area in patients with SMI, and 83% in the anterior area and 17% in the inferior area in patients with painful ischemia. However, the size of RD was significantly smaller in patients with SMI, i.e. 14.6 +/- 6.1 segments in patients with SMI and 18.7 +/- 8.3 segments in patients with painful ischemia (p < 0.05). Although a significantly higher proportion of patients with painful ischemia (48%) underwent PTCA or CABG as their initial therapy as compared to those with SMI (16%), there was no significant difference in the cardiac event rate between the two groups initially treated medically. Among patients with stable angina, those with SMI may have a smaller amount of ischemic myocardium and may be older in a greater proportion than those with painful ischemia. Dipyrimadole thallium imaging is useful in the assessment of SMI in the elderly.
The clinical significance of silent myocardial ischemia (SMI) in the elderly was assessed in 91 patients with Q wave infarction who showed ischemic ST depression during treadmill stress testing, as well as reversible defect (RD) during dipyridamole thallium imaging. They were divided into two groups (47 patients with silent ST depression and 44 patients with painful ST depression) and compared for scintigraphic and coronary arteriographic features, and prognosis. There was no significant difference in age, gender and site of infarction between the two groups. The prevalence of single and double vessel coronary stenosis was higher in patients with SMI (66%) than in those with painful ischemia (p < 0.05). The results of treadmill stress testing showed a longer exercise duration (4.7 +/- 1.7 vs. 4.1 +/- 1.8 min) and higher maximal heart rate (138 +/- 15/vs. 126 +/- 20/min) in patients with SMI than in those with painful ischemia (p < 0.01). Dipyridamole thallium imaging revealed a larger infact (18.8 +/- 9.1 vs. 14.6 +/- 10.2 segments) in patients with SMI than in those with painful ischemia (p < 0.05). The prevalence of RD in the area of infarction was also higher in patients with SMI (74%) than in those with painful ischemia (45%) (p < 0.05). Although a higher proportion of the patients with painful ischemia (42%) underwent CABG or PTCA as their initial therapy, compared with those with SMI (25%) (ns), there was no difference in the cardiac event rate between the two groups who were initially treated medically. Dipyridamole thallium imaging is useful in the assessment of SMI in elderly patients with Q wave myocardial infarction. Those with SMI may have a larger infarct and a higher prevalence of ischemia localized within the infarction than those with painful ischemia.
In this study 112 elderly inpatients (55 men, 57 women) were recruited. 1. Twelve elderly inpatients (5 men, 7 women) aged 82.5 +/- 7.4 years (M +/- SD) were investigated during 3 periods of dietary intake: good intake (period I), tube nutrition (period II) and fasting with intravenous fluid infusion (period III). Calorie, protein, carbohydrate, fat and cholesterol intakes were greater in period I than in periods II and III. Serum total and LDL cholesterols were lowest in period III, when serum HDL cholesterol, triglyceride and total protein were lower in period III than in period I. 2. One hundred elderly inpatients (50 men, 50 women) were divided into 4 groups according to type of decreased serum lipid and a control group. Serum total cholesterol only was decreased in group I, both serum total and HDL cholesterols were decreased in group II, both serum total cholesterol and triglyceride were decreased in group III, all 3 lipids were decreased in group IV and lipid levels did not change in the control group. There were 5 patients in group I, 28 patients in group II, 20 patients in group III, 27 patients in group IV and 20 patients in the control group. The patient's age ranged from 80.3 to 88.4 years and body mass index ranged from 14.7 to 18.4 kg/m2. Serum total protein decreased significantly in groups II-IV, to 5.6 to 5.7 g/dl. Serum total protein, and total cholesterol correlated positively (r = 0.525, p < 0.01), as did Calorie ingestion and serum total cholesterol levels (r = 0.554, p < 0.001). Therefore, severe hypocholesterolemia was accompanied by malnutrition and a decrease in Calorie or cholesterol intake. Serum total cholesterol levels during observation decreased most in group IV, followed by group II similar to serum HDL cholesterol levels. The amount of nutrient intake was smallest in group IV resulting in an extreme lowering of all 3 serum lipid levels.
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