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Biomedical subjects

K Oiwa

Publications and source records attributed to K Oiwa.

At least 19 recordsLinked to original sources

The relationship between 24-hour blood pressure readings, subcortical ischemic lesions and vascular dementia.

BACKGROUND: Twenty-four-hour blood pressure (BP) readings have been found to correlate with hypertensive target organ damage. Lacunar infarcts (LI) and white matter lesions (WML) probably represent manifestations of cerebral hypertensive target organ damage. This study was conducted to better delineate the relationships between 24-hour BP measurements, LI/WML and small vessel disease cognitive impairment/vascular dementia (CI/VD). METHODS: Two hundred patients with first-time symptomatic LI were examined with 24-hour BP monitoring. The degree of nocturnal BP dip, (daytime BP - nighttime BP)/daytime BP, was categorized into three groups: dippers (>0.1), nondippers (0-0.1) and reverse dippers (<0). WML were subdivided into periventricular hyperintensities (PVH) and subcortical hyperintensities. RESULTS: The breakdown of patients was: 50% nondippers, 27.5% reverse dippers and 22.5% dippers. Forty-one patients (20.5%) were found to have CI and dementia. Male sex (OR 3.35; 95% CI 1.20-9.34), advanced PVH (OR 14.42; 95% CI 5.62-36.98) and absence of a dipping status (nondipper: OR 12.62; 95% CI 1.37-115.95; reverse dipper: OR 11.95; 95% CI 1.27-112.11) were independently associated with CIVD after multivariate analysis. High nighttime systolic BP (OR 3.93; 95% CI 1.38-11.17), high daytime (OR 2.06; 95% CI 1.03-4.04) and nighttime diastolic BP (OR 2.48; 95% CI 1.13-5.45) and absence of a dipping status (nondipper: OR 2.7; 95% CI 1.03-7.05; reverse dipper: OR 3.78; 95% CI 1.38-10.34) were significantly associated with PVH. CONCLUSIONS: High prevalence of a nondipping status was found in the LI cohort. A nondipping status appears to be directly associated with CIVD independent of PVH. This study indicates the need for further studies to investigate whether or not controlling nighttime BP will help reduce the risk for CI/VD development.

Aged↗

Tomatoes have natural anti-thrombotic effects.

The prevention of arterial thrombotic diseases has a high priority in developed countries. An inappropriate diet may be an important risk factor for thrombotic events. The daily intake of an anti-thrombotic diet may offer a convenient and effective way of prevention. The aim of the present study was to test tomato extracts for anti-thrombotic effects and to identify those varieties that have such an effect. A shear-induced platelet-function test (haemostatometry) was used to test anti-thrombotic potential in vitro. Extracts from those tomato varieties that showed a significant anti-thrombotic activity in vitro were further assessed in vivo, using a laser-induced thrombosis test in mice. One tomato variety (KG99-4) showed significant anti-thrombotic activity both in vitro and in vivo. KG99-4 inhibited not only platelet-rich thrombus formation but also had a thrombolytic effect. It is concluded that haemostatometry can detect and classify the anti-thrombotic potential of fruits and vegetables and offers a simple way of screening for such effects.

Animals↗

A new model to evaluate the diet-induced prothrombotic state, using He-Ne laser-induced thrombogenesis in the carotid artery of apolipoprotein E-deficient and low-density lipoprotein receptor-deficient mice.

Epidemiological studies suggest the high fat content of the Western diet to be responsible for atherosclerosis and its thrombotic complications. Despite such a prevailing view, few animal experiments have so far succeeded in demonstrating enhanced thrombogenicity due to a high fat diet. Even a high fat and a very high cholesterol (1%) diet has failed to demonstrate an enhanced thrombotic reaction in rodents and rabbits. The aim of the present study was twofold. First, we wanted to establish a new, sensitive and specific thrombosis model in mice, which can then be used to study the effect of diets. Second, we intended to employ such a thrombosis model in investigations into the effect of high or low fat diets on thrombosis. The technique described uses a laser to induce thrombus formation in the exposed carotid artery of apolipoprotein E-deficient and low-density lipoprotein receptor-deficient mice. Thrombus formation was recorded on video, analysed by computer, and the size of thrombus was calculated by image analysis software. Thrombotic status was evaluated by analysing a total of 61 individual images of the thrombotic reaction, which were taken over 600 s. The severity of atherosclerosis was assessed by image analysis of the stained elastic fibers. Two kinds of diets were used: the Western type, high fat diet contained 20% fat (w/w) and 0.05% cholesterol (w/w); the low fat diet contained 7% fat, without cholesterol. These diets were on the basis of AIN93G and were given to mice for 4 or 8 weeks. The high fat diet significantly enhanced both the thrombotic reaction and the development of atherosclerosis as compared with the low fat diet.

Animals↗

Twenty-four-hour blood pressure and MRI as predictive factors for different outcomes in patients with lacunar infarct.

BACKGROUND AND PURPOSE: A long-term follow-up study was conducted in patients with lacunar infarct to assess how 24-hour blood pressure monitoring values and MRI findings, in particular lacunar infarcts and diffuse white matter lesions, can predict subsequent development of dementia and vascular events, which include cerebrovascular and cardiovascular events. METHODS: One hundred seventy-seven patients were tracked for a mean of 8.9 years of follow-up. Documented events comprise the development of dementia and the occurrence of vascular events. The predictors for developing dementia and vascular events were separately evaluated by Cox proportional hazards analysis. RESULTS: Twenty-six patients developed dementia (0.17/100 patient-years). Male sex (relative risk [RR], 4.2; 95% CI, 1.2 to 14.7), cognitive impairment (RR, 3.0; 95% CI, 1.0 to 8.5), confluent DWML (moderate: RR, 7.1; 95% CI, 1.6 to 31.5; severe: RR, 35.8; 95% CI, 7.2 to 177.3), and nondipping status (RR, 7.1; 95% CI, 2.2 to 22.0) were independent predictors for dementia. Forty-six patients suffered from vascular events (3.11/100 patient-years). Diabetes mellitus (RR, 5.7; 95% CI, 2.7 to 11.9), multiple lacunae (moderate: RR, 6.4; 95% CI, 2.5 to 15.8; severe: RR, 8.5; 95% CI, 3.1 to 23.3), and high 24-hour systolic blood pressure (>145 mm Hg versus <130 mm Hg) (RR, 10.3; 95% CI, 1.3 to 81.3) were independent predictors for vascular events. CONCLUSIONS: Predictors for developing dementia and vascular events appear to differ. Male sex, confluent diffuse white matter lesions, and nondipping status were independent predictors for subsequent development of dementia, while diabetes mellitus, multiple lacunae, and high 24-hour systolic blood pressure were independent predictors for vascular events.

Aged↗

An in vitro assay reveals essential protein components for the "catch" state of invertebrate smooth muscle.

"Catch," a state where some invertebrate muscles sustain high tension over long periods of time with little energy expenditure (low ATP hydrolysis rate) is similar to the "latch" state of vertebrate smooth muscles. Its induction and release involve Ca(2+)-dependent phosphatase and cAMP-dependent protein kinase, respectively. Molecular mechanisms for catch remain obscure. Here, we describe a quantitative microscopic in vitro assay reconstituting the catch state with proteins isolated from catch muscles. Thick filaments attached to glass coverslips and pretreated with approximately 10(-4) M free Ca(2+) and soluble muscle proteins bound fluorescently labeled native thin filaments tightly in catch at approximately 10(-8) M free Ca(2+) in the presence of MgATP. At approximately 10(-4) M free Ca(2+), the thin filaments moved at approximately 4 microm/s. Addition of cAMP and cAMP-dependent protein kinase at approximately 10(-8) M free Ca(2+) caused their release. Rabbit skeletal muscle F-actin filaments completely reproduced the results obtained with native thin filaments. Binding forces >500 pN/microm between thick and F-actin filaments were measured by glass microneedles, and were sufficient to explain catch tension in vivo. Synthetic filaments of purified myosin and twitchin bound F-actin in catch, showing that other components of native thick filaments such as paramyosin and catchin are not essential. The binding between synthetic thick filaments and F-actin filaments depended on phosphorylation of twitchin but not of myosin. Cosedimentation experiments showed that twitchin did not bind directly to F-actin in catch. These results show that catch is a direct actomyosin interaction regulated by twitchin phosphorylation.

Animals↗

X-ray diffraction evidence for the lack of stereospecific protein interactions in highly activated actomyosin complex.

The structure of actomyosin complex while hydrolyzing ATP was investigated by recording X-ray diffraction patterns from rabbit skeletal muscle fibers, in which exogenously introduced rabbit skeletal subfragment-1 (S1) was covalently cross-linked to the endogenous actin filaments in rigor by 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC). Approximately two-thirds of the introduced S1 was cross-linked. The cross-linking procedure did not affect the profile of the S1-induced enhancement of the actin-based layer line reflections in rigor, indicating that the acto-S1 interactions remained highly stereospecific. In the presence of ATP, the MgATPase of the S1 was highly activated regardless of calcium levels, presumably because the availability of the stereospecific binding sites for both proteins was maximized by the cross-linking. However, the diffraction pattern in the presence of ATP was striking in that the intensity profile of the strong 1/5.9 nm(-1) layer lines was indistinguishable from that from bare actin filaments, despite the fact that the majority of the S1 was still associated with actin. The change of the intensity profiles upon addition of ATP was completely reversible. Model calculations showed that this result can be explained if the S1 is not only swinging around its pivoting point, but the pivoting point itself is also moving on the actin surface in a range of a few nanometers. The results suggest that the stereospecific binding sites, which have been considered important for actomyosin cycling, are paradoxically left unoccupied for most of the time in this highly activated actomyosin complex.

Actins↗

Controlling the direction of kinesin-driven microtubule movements along microlithographic tracks.

Motor proteins are able to move protein filaments in vitro. However, useful work cannot be extracted from the existing in vitro systems because filament motions are in random directions on two-dimensional surfaces. We succeeded in restricting kinesin-driven movements of microtubules along linear tracks by using micrometer-scaled grooves lithographically fabricated on glass surfaces. We also accomplished the extraction of unidirectional movement from the bidirectional movements along the linear tracks by adding arrowhead patterns on the tracks. These "rectifiers" enabled us to construct microminiturized circulators in which populations of microtubules rotated in one direction, and to actively transport microtubules between two pools connected by arrowheaded tracks in the fields of micrometer scales.

Absorption↗

Dynamic behavior of microtubules during dynein-dependent nuclear migrations of meiotic prophase in fission yeast.

During meiotic prophase in fission yeast, the nucleus migrates back and forth between the two ends of the cell, led by the spindle pole body (SPB). This nuclear oscillation is dependent on astral microtubules radiating from the SPB and a microtubule motor, cytoplasmic dynein. Here we have examined the dynamic behavior of astral microtubules labeled with the green fluorescent protein during meiotic prophase with the use of optical sectioning microscopy. During nuclear migrations, the SPB mostly follows the microtubules that extend toward the cell cortex. SPB migrations start when these microtubules interact with the cortex and stop when they disappear, suggesting that these microtubules drive nuclear migrations. The microtubules that are followed by the SPB often slide along the cortex and are shortened by disassembly at their ends proximal to the cortex. In dynein-mutant cells, where nuclear oscillations are absent, the SPB never migrates by following microtubules, and microtubule assembly/disassembly dynamics is significantly altered. Based on these observations, together with the frequent accumulation of dynein at a cortical site where the directing microtubules interact, we propose a model in which dynein drives nuclear oscillation by mediating cortical microtubule interactions and regulating the dynamics of microtubule disassembly at the cortex.

Biological Transport↗

Twenty-four-hour blood pressure changes in the course of lacunar disease.

BACKGROUND: Changes in blood pressure (BP) over time have not been considered in investigations on the relationship between BP and cerebrovascular disease (CVD). OBJECTIVE: To investigate BP changes throughout a 24-hour period in lacunar infarct patients with different outcomes. METHODS: Twelve control subjects (group 1) and 56 patients with symptomatic lacunar infarcts were studied. The infarct patients were divided into three groups: group 2, 25 patients with a fair outcome without any cerebrovascular attack or progressive dementia (mean follow-up period: 4.4 years); group 3, 14 patients with worsening of clinical dementia rating and silent lesions, which included lacunae and diffuse white matter lesions (4.5 years), and group 4, 17 patients who developed symptomatic infarcts (1.7 years). MRIs and ambulatory BP monitoring were performed for each patient on two separate occasions. No patient was treated with antihypertensive agents during the course of the study. RESULTS: In group 2, the second measurements were significantly higher than the first for 24-hour systolic BP (SBP), daytime SBP, 24-hour diastolic BP (DBP), daytime DBP (p < 0.01, for all) and nighttime DBP (p < 0.05). In group 3, the second measurements were significantly lower than the first for 24-hour SBP, daytime SBP, 24-hour DBP, and daytime DBP (p < 0.01, for all). In group 4, the second measurements were significantly lower than the first for 24-hour SBP and daytime SBP (p < 0.01). The correlation between BP and pulse rate became positive for group 2 in second measurements, but was not positive for groups 3 and 4. CONCLUSIONS: BP tended to elevate over time in patients with a fair outcome. In contrast, BP tended to decrease in those who developed dementia and symptomatic infarct. Autonomic functions including sympathetic activity might play a role in changes in BP in lacunar infarct patients during the course of disease.

Aged↗

[Mechanisms involved in large subcortical infarcts].

Large subcortical infarcts(maximum diameter of infarct > or = 20 mm) result from various stroke patterns, including striatocapsular infarcts (SCI), corona radiata infarcts, centrum semiovale infarcts, and internal borderzone infarcts. A systematic investigation of stroke pathogenesis involved in large subcortical infarcts, however, has not been performed. This study attempted to clarify the stroke mechanisms involved in large subcortical infarcts, by examining 50 patients with large subcortical infarcts out of 430 ischemic stroke patients consecutively registered in our department. The subjects were divided into two groups according to the vascular territories involved on the MRI: 1) the lenticulostriate arteries group for 39 patients whose infarcts were restricted to within the vicinity of the lenticulostriate arteries; 2) the internal borderzone group for 11 patients whose infarcts mainly involved the internal borderzone (the upper part of the corona radiata and the centrum semiovale) between the territories of the deep perforating branches from the basal cerebral arteries and the medullary branches from the superficial pial arteries. Stroke pathogenesis were classified into the following 6 categories: A) cardiogenic embolism, 9 patients; B) artery-to-artery embolism, 6 patients; C) cryptogenic embolism, 2 patients; D) thrombotic MCA (M1) occlusion, 9 patients; E) thrombotic ICA occlusion, 10 patients; F) undetermined cause, 14 patients. The lenticulostriate arteries group consisted of 9 patients with cardiogenic embolism, 6 with artery-to-artery embolism, 2 with cryptogenic embolism, 8 with thrombotic M1 occlusion, and 14 with undetermined cause. The internal borderzone group consisted of 10 patients with thrombotic ICA occlusion and 1 patient with thrombotic M1 occlusion. The stroke pathogenesis of the undetermined cause is considered to be thrombotic occlusion at the orifice of the lateral lenticulostriate artery, a so-called "branch atheromatous disease (BAD)". The patients in this group experienced a gradual onset, and did not have a cardiac source of the embolism or proximal large artery disease. Among the patients reported as having SCI, BAD may play a role in some cases, especially in those whose the cause was classified as "undetermined". In conclusion, the lenticulostriate arteries group exhibited a higher frequency of cerebral embolisms (cardiogenic embolism, artery-to-artery embolism, and cryptogenic embolism) and thrombotic M1 occlusion, whereas the internal borderzone group had a higher frequency of thrombotic ICA occlusion.

Aged↗

Catchin, a novel protein in molluscan catch muscles, is produced by alternative splicing from the myosin heavy chain gene.

Molluscan catch muscles contain polypeptides of 110-120 kDa in size which have the same partial amino acid sequences as those of the myosin heavy chain (MHC). Here we provide evidence that these polypeptides are major components only of the catch-type muscles (their estimated molar ratio to MHC is approximately 1:1) and they are alternative products of the MHC gene. Northern blot analysis of total RNA from Mytilus galloprovincialis catch muscles was carried out with fragments from the 3'-end of the MHC cDNA as probes. We detected two bands of 6.5 kb and 3.5 kb. The former corresponds to the MHC mRNA, and the latter is an mRNA coding for catchin, a novel myosin rod-like protein. By using a 5'-rapid amplification of cDNA ends (RACE) PCR method, the full-length cDNA of Mytilus catchin was cloned. It codes for a protein with a unique N-terminal domain of 156 residues (rich in serine, threonine, and proline), which includes a phosphorylatable peptide sequence. The rest of the sequence is identical with the C-terminal 830 residues of the MHC. We also analyzed Mytilus and scallop (Argopecten irradians) genomic DNAs and found that the 5'-end of the cDNA sequence was located in a large intron of the MHC gene in both species. Since catchin is abundantly expressed only in catch muscles and it is phosphorylatable, we suggest that it may play an important role in the catch contraction of molluscan smooth muscles.

Alternative Splicing↗

Comparative single-molecule and ensemble myosin enzymology: sulfoindocyanine ATP and ADP derivatives.

Single-molecule and macroscopic reactions of fluorescent nucleotides with myosin have been compared. The single-molecule studies serve as paradigms for enzyme-catalyzed reactions and ligand-receptor interactions analyzed as individual stochastic processes. Fluorescent nucleotides, called Cy3-EDA-ATP and Cy5-EDA-ATP, were derived by coupling the dyes Cy3.29.OH and Cy5.29.OH (compounds XI and XIV, respectively, in, Bioconjug. Chem. 4:105-111)) with 2'(3')-O-[N-(2-aminoethyl)carbamoyl]ATP (EDA-ATP). The ATP(ADP) analogs were separated into their respective 2'- and 3'-O-isomers, the interconversion rate of which was 30[OH(-)] s(-1) (0.016 h(-1) at pH 7.1) at 22 degrees C. Macroscopic studies showed that 2'(3')-O-substituted nucleotides had properties similar to those of ATP and ADP in their interactions with myosin, actomyosin, and muscle fibers, although the ATP analogs did not relax muscle as well as ATP did. Significant differences in the fluorescence intensity of Cy3-nucleotide 2'- and 3'-O-isomers in free solution and when they interacted with myosin were evident. Single-molecule studies using total internal reflection fluorescence microscopy showed that reciprocal mean lifetimes of the nucleotide analogs interacting with myosin filaments were one- to severalfold greater than predicted from macroscopic data. Kinetic and equilibrium data of nucleotide-(acto)myosin interactions derived from single-molecule microscopy now have a biochemical and physiological framework. This is important for single-molecule mechanical studies of motor proteins.

Actins↗

Inner-arm dynein c of Chlamydomonas flagella is a single-headed processive motor.

Axonemal dyneins are force-generating ATPases that produce movement of eukaryotic cilia and flagella. Several studies indicate that inner-arm dyneins mainly produce bending moments in flagella and that these motors have inherent oscillations in force and motility. Processive motors such as kinesins have high duty ratios of attached to total ATPase cycle (attached plus detached) times compared to sliding motors such as myosin. Here we provide evidence that subspecies-c, a single-headed axonemal inner-arm dynein, is processive but has a low duty ratio. Ultrastructurally it is similar to other dyneins, with a single globular head, long stem and a slender stalk that attaches to microtubules. In vitro studies of microtubules sliding over surfaces coated with subspecies-c at low densities (measured by single-molecule fluorescence) show that a single molecule is sufficient to move a microtubule more than 1 microm at 0.7 microm s(-1). When many motors interact the velocity is 5.1 microm s(-1), fitting a duty ratio of 0.14. Using optical trap nanometry, we show that beads carrying a single subspecies-c motor move processively along the microtubules in 8-nm steps but slip backwards under high loads. These results indicate that dynein subspecies-c functions in a very different way from conventional motor proteins, and has properties that could produce self-oscillation in vivo.

Animals↗

Myosin light-chain kinase of smooth muscle stimulates myosin ATPase activity without phosphorylating myosin light chain.

Myosin light-chain kinase (MLCK) of smooth muscle is multifunctional, being composed of N-terminal actin-binding domain, central kinase domain, and C-terminal myosin-binding domain. The kinase domain is the best characterized; this domain activates the interaction of smooth-muscle myosin with actin by phosphorylating the myosin light chain. We have recently shown that the Met-1-Pro-41 sequence of MLCK binds to actin to inhibit this interaction. However, it is not known whether the myosin-binding domain modifies the actin-myosin interaction. We designed MLCK.cDNA to overexpress the Asp-777-Glu-972 sequence in Escherichia coli. The purified Asp-777-Glu-972 fragment, although devoid of the kinase activity, exerted a stimulatory effect on the ATPase activity of dephosphorylated myosin (Vmax = 7.36 +/- 0.44-fold, Km = 1.06 +/- 0. 20 microM, n = 4). When the N-terminal 39 residues of the fragment were deleted from the fragment, the resultant fragment, Met-816-Glu-972, lost the stimulatory activity. We synthesized the Ala-777-Ser-815 peptide that was deleted from the fragment and confirmed its stimulatory effect of the peptide (Vmax = 3.03 +/- 0. 22-fold, Km = 6.93 +/- 1.61 microM, n = 3). When this peptide was further divided into Asp-777-Met-795 and Ala-796-Ser-815 peptides, the stimulatory activity was found in the latter. We confirmed that the myosin phosphorylation did not occur during the experiments with the above fragments and peptides. Therefore, we suggest that phosphorylation is not obligatory for smooth-muscle myosin not to be active.

Animals↗

[Coagulation and fibrinolytic activation in lacunar infarct patients].

Lacunar infarcts are related to occlusion of penetrating arteries. Lipohyalinosis affects the smaller arteries 40-200 microns in diameter, and atherosclerosis involves larger arteries 200-850 microns in diameter. We hypothesized that the processes of thrombus formation might be different among these two kinds of lacuner infarcts, including those caused by lipohyalinosis and atherosclerosis. We studied acute coagulation and fibrinolytic activation in lacunar infarct patients which were divided into two groups according to their size: smaller lacunar group and larger lacunar group. Then we divided lacunar infarct patients into two groups in terms of the progression of motor deficits: those who showed the progression and those did not. And coagulation and fibrinolytic activation were compared each other. One hundred and twenty four patients were enrolled in this study, including 34 control subjects, 39 patients with smaller lacune (3 mm-10 mm in diameter), 28 patients with large lacune (10 mm-20 mm), and 23 patients with atherothrombotic infarcts confirmed by angiography. The levels of TAT activity in large lacune and atherothrombotic infarcts were significantly higher than those in control subjects (p = 0.009, p < 0.0001, respectively), whereas those in small lacune were not. Also, the levels of D-dimer activity in large lacune and atherothrombotic infarcts were significantly higher than those in control subjects (p = 0.0003, p < 0.0001, respectively), whereas those in small lacune were not. The progression of motor deficits were more frequently recognized in large lacune than in small lacune: three patients out of 39 small lacune patients and 22 patients out of 28 large lacune patients (difference was significant, p = 0.001). The level of TAT activity in patients who showed progression of motor deficits was significantly higher than that in those who did not (p = 0.0002), whereas the difference of the levels of D-dimer activity in two groups did not reach significant differencial levels. The process of thrombin and fibrin formation in large lacunar infarcts which are related to microatheroma and atheroscrelosis appears to be different from that in small lacunar infarcts. Antiplatelet and anticoagulation therapy should be tailored to large lacunar infarct patients.

Aged↗

Direct observation of a central bare zone in a native thick filament isolated from the anterior byssus retractor muscle of Mytilus edulis using fluorescent ATP analogue.

To investigate the existence of a central bare zone in native thick filaments isolated from the anterior byssus retractor muscle (ABRM) of blue mussels (Mytilus edulis), the filaments were observed by fluorescence and dark-field microscopy after being incubated in the presence of Ca2+ with the fluorescent ATP analogue, Cy3-EDA-ATP. Filaments appeared under dark-field illumination as thin rods with tapered ends of length 5-30 microm. Fluorescence microscopy revealed that Cy3-EDA-ATP was bound to these filaments, except near their center. Although the boundary between this central non-fluorescent zone and fluorescent regions was not clearly defined, there was a trend for the width of the central non-fluorescent zone to increase with thick filament length (correlation coefficient = 0.45; n = 142). When Cy3-EDA-nucleotides bound to thick filaments were displaced by excess ATP, fluorescent images disappeared with a rate constant of 0. 024 s-1, close to the turnover rate of Cy3-EDA-ATP by myosin on the native thick filaments. These results indicate that each native thick filament isolated from the ABRM has a central bare zone, but its boundary was not sharply resolved.

Adenosine Triphosphate↗

Adverse effect of nighttime blood pressure on the outcome of lacunar infarct patients.

BACKGROUND AND PURPOSE: Antihypertensive therapy has dramatically reduced the incidence of stroke recurrence; however, recent studies have suggested that the excessive lowering of blood pressure (BP) could cause ischemic cerebral lesions. We conducted a prospective study using MRI and ambulatory blood pressure monitoring to elucidate the appropriate BP control level for the prevention of silent and symptomatic cerebral infarction. METHODS: We studied 105 patients with symptomatic lacunar infarcts who underWent repeated MRI and 24-hour BP monitoring in the period between the two MRI examinations. The patients were divided into five groups according to their outcome as follows: group 1, those who showed neither symptomatic episodes nor the development of new silent lesions detected by repeated MRI; group 2, those who only showed the development of silent lacunae; group 3, those who showed development of diffuse white matter lesions only; group 4, those who showed the development of both silent lacunae and diffuse white matter lesions; and group 5, those who showed symptomatic cerebrovascular disease. Groups 2 through 5 were then compared with group 1 with respect to the ambulatory BP values. RESULTS: The average follow-up period was 3.2 +/- 2.6 years (mean +/- SD). In all patients in group 4 and group 5, nighttime systolic BPs were significantly higher than in group 1 (both P<.01), and the magnitude of the nocturnal systolic BP dip and diastolic BP dip in group 4 and group 5 were significantly smaller than in group 1 (all P<.01). In patients who took antihypertensive agents, the 24-hour systolic and diastolic BPs and nighttime systolic and diastolic BPs in group 4 were significantly higher than in group 1 (P<.01, P<.01, P<.001, P<.01, respectively). The magnitude of the nocturnal systolic and diastolic BP dip in group 5 was significantly smaller than in group 1 (both P<.01). CONCLUSIONS: A high average ambulatory BP, especially nighttime BP, and a reduced nocturnal BP dip may have an adverse effect on the development of silent ischemic lesions and symptomatic stroke attack in patients with lacunar infarcts.

Aged↗

Unidirectional movement of fluorescent microtubules on rows of dynein arms of disintegrated axonemes.

Tetramethylrhodamine-labelled microtubules were observed to move on rows of dynein arms of sea urchin sperm axonemes exposed by elastase-induced sliding disintegration. The microtubules moved towards the flagellar tip at a velocity of 3.1+/-2.1 microm second-1 (mean +/- s.d., n=53) in the presence of 0.1 mM ATP at 22 degrees C, but none moved towards the sperm head. We also examined the polarity of microtubule binding to axonemal doublet microtubules in the absence of ATP by using microtubules brightly labelled at their minus-ends. In 140 of 210 microtubules studied, they bound to axonemal microtubules with a parallel polarity. These results suggest that tightly packed dynein arms on the outer doublet microtubules of sperm axoneme preferentially bind microtubules to themselves with the same polarity as that of the axoneme and that they generate a force to move only these microtubules in the direction away from the sperm head.

Animals↗