The role of tissue factor in ischemic reperfusion injury: (ii). The expression of tissue factor of the liver in hepatic injury.
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Animals↗
Biomedical subjects
N Yoshimura
Publications and source records attributed to N Yoshimura.
Developmental and injury induced plasticity in the micturition reflex pathway.
The storage and periodic elimination of urine are dependent upon neural circuits in the brain and spinal cord that co-ordinate the activity of the urinary bladder, the urethra and the striated urethral sphincter. This study utilized anatomical, electrophysiological and pharmacological techniques to examine: (1) the organization of the parasympathetic excitatory reflex mechanisms that control the urinary bladder of the rat and the cat; and (2) the changes in these reflexes during postnatal development and after spinal cord injury. In normal adult cats and rats, the parasympathetic excitatory input to the bladder is dependent upon a spinobulbospinal reflex pathway that is activated by myelinated (Adelta) bladder afferents and that passes through an integrative center (the pontine micturition center, PMC) in the rostral brain stem. Transneuronal tracing studies using pseudorabies virus as well as physiological methods have revealed that the PMC is located in close proximity to the locus coeruleus. Single unit recordings indicate that neurons in the PMC respond to afferent input from the bladder and are excited prior to or during reflex bladder contractions. Glutamic acid is the major excitatory transmitter in the micturition reflex pathway. Glutamatergic transmission which is mediated by AMPA/kainate and NMDA receptors can be modulated by a variety of other transmitters. In neonatal animals, a spinal micturition reflex is activated by somatic afferent fibers from the perigenital region. This reflex is suppressed during postnatal development, but can be unmasked in adult animals following spinal cord injury. Spinal injury also causes the emergence of a spinal bladder-to-bladder reflex which in the cat is activated by capsaicin-sensitive C-fiber bladder afferents. Patch clamp studies in spinal cord slice preparations indicate that developmental and spinal cord injury induced plasticity in sacral parasympathetic reflex pathways is due in part to alterations in glutamatergic excitatory transmission between interneurons and preganglionic neurons. Changes in the electrical properties of bladder afferent pathways may also contribute to the reorganization of bladder reflexes in paraplegic animals.
Animals↗
Effects of spinal cord injury on neurofilament immunoreactivity and capsaicin sensitivity in rat dorsal root ganglion neurons innervating the urinary bladder.
The effect of chronic spinal cord transection on neurofilament immunoreactivity and capsaicin sensitivity of L6 and S1 dorsal root ganglion neurons innervating the urinary bladder was examined using an antibody (RT97) against 200,000 mol. wt subunit of neurofilament protein and a cobalt uptake assay, respectively. Bladder afferent neurons labelled by axonal transport of a fluorescent dye (Fast Blue) injected into the bladder wall were identified in sections of intact dorsal root ganglia and among dissociated neurons in short-term culture. Approximately two thirds of bladder afferent neurons from spinal intact rats were neurofilament-poor (i.e. C-fibre neurons). These neurons were on average 37% smaller in cross-sectional area than neurofilament-rich neurons (A delta-fibre neurons). In spinal intact rats, 78% of neurofilament-poor dissociated bladder afferent neurons were sensitive to capsaicin, while only 6.2% of neurofilament-rich neurons were capsaicin-sensitive. Dissociated bladder afferent neurons from spinal transected animals had larger diameters (34.2 +/- 1.1 microns) than those from spinal intact animals (29.2 +/- 1.2 microns). In tissue sections from dorsal root ganglia, the mean cross-sectional area of bladder afferent neuron profiles in spinal transected animals was also larger by approximately 35% than in spinal intact animals. Immunoreactivity to neurofilament protein which occurred in 32% of bladder afferent neurons in spinal intact animals was detected in a larger percentage (56% to 62%) of neurons from spinal transected animals. Conversely, the population of capsaicin-sensitive dissociated neurons was reduced from 55% in spinal intact rats to 38% in spinal transected rats. These results indicate that spinal cord injury induces functional and morphological plasticity in C-fibre visceral afferent neurons innervating the urinary bladder.
Animals↗
Bone loss in Great Britain and Japan: a comparative longitudinal study.
Hip fracture incidence is lower in Japan than in the West. Although differences have been found in peak bone mass and hip geometry between white and Japanese populations, these do not fully explain the difference in hip fracture rates. Variation in the rates of involutional bone loss may be an additional contributing factor. We address this issue in a prospective epidemiological study comparing bone loss rate among elderly people in Britain and Japan. Two population-based studies of bone loss rate in a British and a Japanese cohort were performed. Annual bone loss rates were obtained for 172 Hertfordshire men and 143 Hertfordshire women of mean age 66 years, and a questionnaire administered to obtain information on known confounding lifestyle factors. Eighty-six Japanese men and 90 Japanese women of mean age 69 years completed a similar study in Taiji, Japan. British men and women were heavier than Japanese men and women. Differences in lifestyle were also evident; the British men were less likely to smoke and the women more likely to consume alcohol than their Japanese counterparts. The British population also spent more time walking outdoors. Statistically significant differences between the two populations were apparent in baseline bone mineral density at lumbar spine (p < 0.05) and trochanter (p < 0.001) in men and women with Japanese subjects having lower values. There were also significant differences in bone density at the femoral neck (p < 0.001) between British and Japanese males. Men gained bone at the lumbar spine over the follow-up period in both populations. Bone loss rates were generally greater in the British female population than in Japanese women: the difference was statistically significant at the femoral neck (p < 0.05) and femoral trochanter (p < 0.001). These differences all remained significant after adjustment for differences in age between the two populations. Japanese subjects appear to have lower peak bone mass, but slower bone loss rates in later life than their European counterparts. These differences in bone loss rate help to explain the relatively low hip fracture rates found in Japan.
Absorptiometry, Photon↗
Acetabular dysplasia and hip osteoarthritis in Britain and Japan.
OBJECTIVE: Geographic differences in the prevalence of hip osteoarthritis (OA) have been ascribed to differences in the frequency of acetabular dysplasia among different ethnic groups. However, there are few data on the shape of the acetabulum in various populations around the world. We examined this issue in samples of pelvic radiographs from Britain and Japan. METHODS: Measurements were made on the pelvic radiographs of 1303 men and 195 women, aged 60-75 yr, who attended for i.v. urography in two British centres. These were compared with 99 men and 99 women aged 60-79 yr who were included in a population-based study in a rural community in Japan, and who agreed to undergo standardized pelvic radiography. Acetabular dysplasia was assessed by morphometric measurement of the centre-edge (CE) angle and acetabular depth. RESULTS: The mean CE angle among men was 36 degrees (95% CI 35-37 degrees ) in Britain and 31 degrees (95% CI 29-32 degrees ) in Japan; that in women was 37 degrees (95%, CI 36-38 degrees ) in Britain and 31 degrees (95% CI 29 33 degrees ) in Japan. The mean values of acetabular depth were also significantly (P < 0.001) lower in Japan than in Britain. However, the prevalence of hip OA was lower in Japan (0% in men, 2% in women) than in Britain ( 11% in men, 4.8 / in women). In a random effects model, there were negative relationships between measures of acetabular dysplasia and minimum joint space among individuals. CONCLUSIONS: We conclude that there are marked differences in pelvic morphometry between Britain and Japan. The acetabular dimensions of Japanese subjects are considerably shallower than those of their British counterparts of similar age and sex. Nevertheless, hip OA is more frequent in Britain than in Japan. Further studies are required on the risk factors for hip OA in Oriental populations, in order that the aetiology of this disorder can be better understood.
Acetabulum↗
Dual isotope SPECT in malignant Jacod's syndrome.
A case is presented of metastatic tumor causing Jacod's syndrome: total ophthalmoplegia, blindness, and trigeminal neuralgia. Abnormal soft tissue invading the orbital apex, anterior clinoid process, and cavernous sinus was difficult to assess by CT and MRI, but dual-isotope SPECT including Tc-99m HMDP bone imaging and Tl-201 tumor imaging strongly suggested that the cause of this rare syndrome was a small metastatic tumor. Although the therapeutic effect was also difficult to assess by anatomic imaging alone, dual-isotope SPECT after radiation therapy showed a decline of tumor viability.
Aged↗
Diagnosis of lung cancer using two-phase Tl-201 SPECT and modified retention image to view tumor in the collapsed lung: comparison with bolus CT.
In this report the usefulness of Tl-201 SPECT and modified retention images in the differentiation of lung cancer and postobstructive collapse was studied. Two-phase Tl-201 SPECT was performed in 20 lung cancer lesions in which postobstructive collapse was suspected on CT. Retention imaging was done afterward. Three types of Tl-201 images were compared with the bolus CT images. Bolus CT differentiated lung cancer from postobstructive collapse in 7 of the 20 lesions (35%). Tl-201 SPECT differentiated the two conditions in 9 of 20 lesions (45%) on early Tl-201 SPECT and in 13 of 20 lesions (65%) on delayed imaging. With modified retention images, differentiation was possible in 13 of 20 lesions (65%). By combining delayed Tl-201 SPECT and modified retention images, lung cancer alone could be demonstrated in 18 of 20 lesions (90%). Combined delayed Tl-201 SPECT and modified retention images were more effective than bolus CT in delineating the extent of lung cancer in the presence of postobstructive collapse.
Aged↗
Relationship between ATP synthesis and 201Tl uptake in transformed and non-transformed cell lines.
201Tl tumour imaging is an established procedure, but little is known about its biological significance in transformed and non-transformed cells. In investigating the relationship between 201Tl uptake and intracellular ATP, we wished to determine whether the observed difference in delayed uptake is attributable to re-uptake via Na-K ATPase by using transformed (HeLa) and non-transformed (human fibroblast: hFB) cell lines. In each cell line, ATP was measured using the Luciferin-Luciferase method (LLM). The change in 201Tl uptake was assessed under conditions of mitochondrial suppression. Additionally, we assessed whether glycolysis is involved in 201Tl uptake under conditions of mitochondrial suppression and anaerobic incubation. Re-uptake via Na-K ATPase (HeLa vs hFB: 37.3 vs 24.2%) showed a clear difference in delayed uptake between HeLa and hFB. With HeLa, 201Tl uptake decreased biphasically with a reduction in ATP levels, whereas with hFB a linear correlation was evident. Despite the suppression of mitochondrial potential, a 5% glucose loading accelerated glycolysis with HeLa, and increased ATP (10.0 +/- 4.0%) and 201Tl uptake (16.2 +/- 3.0%). Conversely, neither ATP nor 201Tl uptake increased with hFB. Our results provide evidence that 201Tl uptake in transformed cells is related to enhanced glycolysis as well as mitochondrial ATP synthesis.
2,4-Dinitrophenol↗
Decision analysis for treatment of early stage prostate cancer.
We performed a decision analysis to evaluate the usefulness of pretreatment prediction of clinically significant or insignificant tumor in patients with prostate-specific antigen (PSA)-detected stage T1c prostate cancer nonpalpable on rectal examination. Analysis was done for otherwise healthy subjects with 20 years of life expectancy. The prevalence of insignificant tumor among those with T1c prostate cancer was initially assumed to be 0.2. Quality-adjusted life expectancy was calculated and compared between 2 strategies; one with prediction-based selection of either radical prostatectomy or watchful waiting and the other with unselective assignment of one of the treatments. The selection strategy was superior when the sensitivity and specificity for detecting clinically significant tumor were 0.92 and 0.73, respectively, as reported by Epstein et al. (1994) using criteria of PSA density and Gleason score in a needle biopsy specimen. Sensitivity analysis revealed that the prediction-based selection strategy is preferred, with sensitivity and specificity constant, when the prevalence of insignificant tumor exceeds 0.16. On the other hand, when the prevalence of insignificant tumor is kept constant at 0.2, sensitivity should be 0.85 or higher for the prediction strategy to be preferred. As the prevalence of insignificant tumor among those with T1c prostate cancer increased, the prediction-based selection strategy is preferred with lower values of sensitivity and specificity for detecting significant tumor. These results suggest that a selective treatment strategy of either radical or conservative treatment based on pretreatment prediction for significant tumor is a beneficial alternative to radical prostatectomy unselectively assigned to all patients at the T1c stage, if a reasonable accuracy in prediction is attained.
Decision Support Techniques↗
Ultrasound biomicroscopic images of the anterior chamber angle of a patient with posterior polymorphous dystrophy.
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Adult↗
Energy-dependent redox state of heme a + a3 and copper of cytochrome oxidase in perfused rat brain in situ.
Using the blood-free perfused rat brain, we examined the redox behavior of cytochrome oxidase of two chromophores, heme a + a3 and copper. When perfusate inflow was stopped to induce global ischemia, the reduction of heme a + a3 was triphasic, with a rapid phase, a slow phase, and a second rapid phase. In contrast, the reduction of copper was monophasic after the rapid phase of heme a + a3. The triphasic reduction of heme a + a3 was diminished by energy-depleting treatments, such as addition of an uncoupler. The time course of the reduction of copper was not affected by the energy depletion. During global ischemia the decrease in creatine phosphate nearly paralleled the reduction of heme a + a3, whereas ATP remained at the control level until approximately 60% of heme a + a3 was reduced in the rapid phase. In the slow phase, ATP started to decrease with the reduction of copper. The redox behavior of copper was similar to the slow phase of the reduction of heme a + a3 because of the higher oxygen affinity of copper than of heme a + a3. Therefore, the rapid phase of the reduction of heme a + a3 can be used as an alarm before a decrease in ATP, whereas the reduction of copper indicates a decrease in ATP under severe hypoxia. Thus the copper signal in noninvasive near-infrared spectroscopy is a useful parameter for the clinical setting.
Animals↗
Localized aberrant expression of cytochrome P450 aromatase in primary and metastatic malignant tumors of human liver.
The present study was designed to demonstrate localized aberrant expression of aromatase in primary and metastatic malignant liver tumors. Immunocytochemistry revealed the presence of locally increased aromatase protein in regions around tumors in all specimens from seven primary and seven metastatic liver tumors. This observation was further confirmed by Western blotting analysis and assay of aromatase activity in tumorous, proximal, and distal regions. Western blots showed most intensely immunoreactive bands at the position corresponding to aromatase in proximal tissues where aromatase activities also were higher (2.75 +/- 1.59 pmol/mg.h) than in tumors (0.137 +/- 0.115 pmol/mg.h) and distal tissues (1.90 +/- 1.47 pmol/mg.h), in spite of a gradient decline of NADPH-cytochrome P-450 reductase activity from the distal regions to the tumors. RT-PCR analysis indicated that the aberrant increase in aromatase protein and enzyme activity in the regions proximal to tumors is caused by locally elevated aromatase messenger RNA.
Adult↗
Expression of cell cycle-related genes in dying cells in retinal ischemic injury.
PURPOSE: To investigate whether cell cycle-related genes play a role in neuronal cell death in retinal ischemia-reperfusion injury. METHODS: Retinal ischemia-reperfusion injury was induced in rats by a ligation method and also by increasing the intraocular pressure. After 1 hour-of ischemia, cell death in the retina was studied using the TdT-dUTP terminal nick-end labeling (TUNEL) method, propidium iodide (PI) staining, DNA ladder formation, and ultrastructural studies. Immunohistochemical studies using antibodies against cell cycle-related genes were conducted. Changes in expression of cyclin D1 mRNA were quantitated using competitive quantitative polymerase chain reaction. RESULTS: At 3 hours after reperfusion, cells in the ganglion cell layer were the first to die, followed by those in the inner nuclear layer (at 6 hours) and outer nuclear layer (at 9 hours). Ultrastructural studies revealed condensed nuclei and relatively preserved mitochondria; DNA ladder formation was also detected. Immunostaining was positive for the cell cycle-related gene products c-Jun, cyclin B1, and cyclin D1. The time course of TUNEL-positive cells and that of cells positive for c-Jun or cyclin D1 in the inner nuclear layer was similar. A double-labeling study, using PI or TUNEL, and immunohistochemical analysis revealed that dying cells expressed c-Jun and cyclin D1, whereas cyclin B1 expression was observed in Müller cells. Quantitation of cyclin D1 mRNA revealed an approximate 4-fold increase at 24 hours after reperfusion. CONCLUSIONS: Aberrant expression of cell cycle-related genes may play an important role in the cell death that accompanies retinal ischemia-reperfusion injury.
Animals↗
Upregulation of transforming growth factor-beta after panretinal photocoagulation.
PURPOSE: To determine whether upregulation of transforming growth factor-beta (TGF-beta) gene expression occurs after panretinal photocoagulation (PRP). To quantitate two TGF-beta isoforms in the aqueous and vitreous humors and to localize TGF-beta 2-like immunoreactivities (TGF-beta 2-LI) and TGF-beta 2 mRNA in the retina after PRP. METHODS: PRP was performed on Brown Norway rats by using an argon-green laser. Sensory retina, aqueous and vitreous humors were collected from the rats on days 1, 3, and 7 after PRP, and semiquantitative polymerase chain reaction analyses were carried out. TGF-beta 2 in the aqueous and vitreous humors was quantitated by enzyme-linked immunosorbent assay. Localization of TGF-beta 2-LI was demonstrated by immunohistochemistry, and that of TGF-beta 2 mRNA by in situ reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: Gene expression of both TGF-beta 1 and -beta 2 was upregulated by PRP. Expression of TGF-beta 2 was greater than that of beta 1 (12.8-fold increase versus 3.24-fold increase, respectively, compared with control level on day 3). TGF-beta 2 concentration was increased in the vitreous humor (4.37-fold increase, P < 0.01) but not in the aqueous humor (the same level compared with control) on day 1. TGF-beta 2-LI and TGF-beta 2 mRNA were detected in cells of the outer retinal layer and in retinal pigment epithelial cells adjacent to the laser burns. CONCLUSIONS: PRP upregulates expression of TGF-beta 2 in the retina, and increased TGF-beta 2 concentrations are found in the retina and the vitreous humor. Retinal pigment epithelial cells and sensory retina around the laser burn appear to play a major role in the upregulation.
Animals↗
[Functional difference between the left supplementary motor area and the left premotor area in a task of confrontation naming and word fluency].
We assessed the faculty of confrontation naming and word fluency of the 11 patients afflicted with frontal lobe infarction or hemorrhage. All the patients were right-handed and manifested transcortical motor aphasia due to cerebrovascular diseases. We carried out the Western Aphasia Battery, and we adopted V-A; the naming task involved confrontation naming of 20 objects, and V-B; the word fluency task involved the naming as many animals as possible in a one minute period. Six patients who have lesions in the left medial frontal lobe performed excellency in the confrontation naming task but exhibited poor word fluency, and 5 patients who have lesions in the left dorso-lateral frontal lobe performed poorly in both tasks. This results suggests that the left dorso-lateral frontal lobe is important in confrontation naming, while the left medial frontal lobe is important in word fluency. Mushiake et al. (1991) showed that the premotor area was involved in visually guided sequential movements, and the supplementary motor area was involved internally determined sequential movements in primates. Regarding language function as analogous to movement, confrontation naming is analogous to visually guided movements and word fluency is analogous to internally determined movements. Thus, our results suggest that the functional difference between the left medial frontal lobe, which includes the supplementary motor area, and the left dorso-lateral frontal lobe, which includes the premotor area, which was demonstrated in primates for movement is also true of language function in humans.
Aphasia, Broca↗
[Therapeutic strategy in Fontan procedure].
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Aortic Valve Stenosis↗
Therapeutic effects of dopamine D1/D2 receptor agonists on detrusor hyperreflexia in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned parkinsonian cynomolgus monkeys.
The effects of dopamine receptor agonists on urinary bladder function were evaluated in normal and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned parkinsonian cynomolgus monkeys to investigate the therapeutic efficacy in the treatment of urinary symptoms in Parkinson's disease. Under ketamine anesthesia, cystometrograms exhibited significant reduction in the volume threshold for the micturition reflex in MPTP-lesioned parkinsonian monkeys when compared with those of normal monkeys. The selective dopamine D2 receptor agonist bromocriptine significantly reduced the bladder volume threshold for the micturition reflex by 25 to 30% in both normal and MPTP-lesioned animals. The nonselective D1/D2 receptor agonist pergolide significantly reduced the bladder volume threshold by 22% in normal monkeys, but increased the volume threshold by 50% in MPTP-lesioned parkinsonian monkeys. Another D1/D2 agonist (5R,8R,10R)-6-methyl-8-(1,2,4-triazol-1-ylmethyl) ergoline maleate (BAM-1110) also increased the bladder volume threshold (by 80%) in parkinsonian monkeys without significant effects on the micturition reflex in normal monkeys. The reduction in the volume threshold by bromocriptine in both normal and MPTP-treated groups and by pergolide in normal monkeys was suppressed by pretreatment with the selective D2 antagonist sulpiride, whereas the increment in the volume threshold by pergolide and BAM-1110 in parkinsonian monkeys was antagonized by pretreatment with the selective D1 antagonist SCH 23390, but not by sulpiride. These findings suggest that concurrent activation of D1/D2 receptors, rather than selective stimulation of D2 receptors, might be beneficial for treating urinary symptoms caused by detrusor hyperreflexia in Parkinson's disease.
Animals↗
Protective effect of adult T-cell leukemia-derived factor on retinal ischemia-reperfusion injury in the rat.
PURPOSE: To evaluate the protective effects of recombinant adult T-cell leukemia- derived factor (ADF)-human thioredoxin against ischemia-reperfusion injury in the rat retina. METHODS: Retinal ischemia was induced in rats by increasing the intraocular pressure to 110 mm Hg for 60 minutes. Various doses of recombinant human ADF (rhADF) or vehicle were administered intravenously before ischemia induction and immediately after reperfusion. The degree of retinal damage was assessed by electroretinogram (ERG) recording, by measuring the inner retinal thickness, and by counting the number of TdT-dUTP terminal nick-end labeling (TUNEL)-positive cells in the inner nuclear layer. RESULTS: The amplitudes of the ERG b-wave and oscillatory potentials were increased significantly by treatment before ischemia and after reperfusion with 0.5 mg or 5 mg rhADF and by treatment after reperfusion with 1 mg rhADF, compared with those of vehicle-treated control rats (P < 0.01). On day 28 after reperfusion, the thickness of the inner retina of control rats and of rats treated before ischemia and after reperfusion with 0.5 mg rhADF were 46.1+/-6.4 microm and 78.5+/-8.9 microm, respectively (P < 0.01). The number of TUNEL-positive cells on days 1 and 2 after reperfusion was decreased significantly by treatments with 0.5 mg rhADF compared with the number of TUNEL-positive cells in control rats (P < 0.01). CONCLUSIONS: Electrophysiologic and histologic studies showed that ischemia for 60 minutes produces severe damage in vehicle-treated control rat retina, particularly in the inner retinal layer. Intravenous injection of rhADF protects the rat retina from ischemia-reperfusion injury.
Animals↗