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Biomedical subjects

S Konno

Publications and source records attributed to S Konno.

At least 73 records · Page 4Linked to original sources
PubMed1999

Glyoxalase I activity in human prostate cancer: a potential marker and importance in chemotherapy.

PURPOSE: To provide information on the activity of Gly-I in prostate cancer. MATERIALS AND METHODS: We performed qualitative Gly-I assay on prostate tissues. RESULTS: Gly-I activity between prostate cancer and noncancerous specimens differed substantially and significantly, although such activity also varied somewhat among cancer specimens. CONCLUSIONS: Gly-I activity is indeed higher in cancerous than in noncancerous specimens, suggesting that it may play a role in prostate cancer homeostasis and survival.

Biomarkers, Tumor↗
PubMed1998

Report on the preparation of deuterium-labelled aconitine and mesaconitine and their application to the analysis of these alkaloids from body fluids as internal standard.

Improved analysis of aconitine and mesaconitine, highly toxic compounds from Aconitum species, in body fluids by gas chromatography-selected ion monitoring with their deuterium-labelled analogues as internal standards (I.S.s) is described. Deuterium-labelled analogues of aconitine and mesaconitine were synthesized by the substitution of the N-alkyl group for a deuterium-labelled one. The mass spectra of the derivatives of the deuterium labels closely resembled that of the nonlabelled compounds except for an obvious mass shift produced by substitution of the deuterium atoms at N-alkyl groups. Using these deuterium-labelled compounds as I.S.s, the standard curves for aconitine and mesaconitine were linear (r2=0.999 each) in the concentration range of 50 pg to 50 ng, respectively. The detection limit of the alkaloids was 10 pg each per injection. The recovery, accuracy and precision of the analysis were evaluated with three different concentration of spiked human blood and urine (n=5 each). The recovery rates ranged from 97.6% to 101.3% and the standard deviations of the interseries ranged from 2.1% to 3.9%. These I.S.s give us a more precise analysis and may be useful in examining the behavior of these alkaloids in the human body.

Aconitine↗
PubMed1998

Chronic double-level cauda equina compression. An experimental study on the dog cauda equina with analyses of nerve conduction velocity.

STUDY DESIGN: Nerve conduction velocity was studied in the dog cauda equina subjected to chronic double-level compression. OBJECTIVES: To analyze the effects of chronic double-level cauda equina compression. SUMMARY OF BACKGROUND DATA: Double-level cauda equina compression produces more symptoms in patients and more changes in acute experimental set-ups than does single-level compression. However, there have been no controlled, experimental studies on chronic double-level compression. METHODS: A total of 20 dogs were anesthetized. Two balloons were placed under the lamina of the seventh lumbar vertebra and the first sacral vertebra, respectively. One week (10 mm Hg, n = 5; 0 mm Hg, n = 5) and 1 month (10 mm Hg, n = 5; 0 mm Hg, n = 5) after inflation with a viscous substance, nerve conduction velocity was studied by local electrical stimulation and recording of muscle action potentials in the tail muscles. RESULTS: Nerve conduction velocity was determined over the cranial balloon, the caudal balloon, and both balloons. The data were similar for all three recordings. After 1 week there was a significant reduction in nerve conduction velocity induced by 10 mm Hg, compared with that induced by 0 mm Hg, which showed normal conditions. However, after 1 month this initial reduction in nerve conduction velocity had recovered partially. The reduction was similar to that described for single-level compression in a previous study in which the same compression model was used. CONCLUSIONS: Unlike the acute situation, chronic double-level compression does not induce more changes than single-level compression after 1 week, although the recovery after 1 month of compression is less complete after double-level compression. This less complete recovery may be a result of an adaptation of the nerve tissue and the vascularization of the cauda equina nerve roots to the applied pressure.

Action Potentials↗
PubMed1998

The effects of brefeldin A (BFA) on cell cycle progression involving the modulation of the retinoblastoma protein (pRB) in PC-3 prostate cancer cells.

PURPOSE: To investigate the effects of brefelding A (BFA) on the growth of the androgen-independent human prostate cancer PC-3 cells, focusing on cell cycle regulation. MATERIALS AND METHODS: BFA is a fungal macrocyclic lactone with an antiviral activity. PC-3 cells were cultured with various concentrations of BFA for indicated times and cell growth was monitored at each time point. Cell cycle analysis was performed to explore the mechanism of BFA-induced growth inhibition. To further investigate the cell cycle regulation, cell cycle-controlling factors, such as the retinoblastoma gene product (pRB) and its regulatory components cdk2, cdk4, and cyclin D1, were analyzed by Western immunoblots. RESULTS: BFA was a potent growth inhibitor at a concentration of 30 ng./ml., resulting in a > 70% reduction in cell number at 3 days. Cell cycle analysis revealed a cell arrest in the G1 to S phase transition. Western blots further showed that BFA induced dephosphorylation of pRB accompanied by down regulation of cdk2, cdk4, and cyclin D1 expression. The extended pRB dephosphorylation in control cell lysates was also observed by the addition of BFA-treated lysates, but was prevented by the inclusion of phosphatase inhibitors in assay mixtures. CONCLUSION: These results suggest that BFA may be a potent cell cycle modulator, which post-translationally regulates pRB phosphorylation possibly by down-regulating cdk2, cdk4, and cyclin D1 and/or by up-regulating a phosphatase(s) capable of dephosphorylating pRB. Thus, BFA-induced growth inhibition in PC-3 cells appears to be at least partially due to the modulation of a pRB-mediated growth pathway.

Brefeldin A↗
PubMed1998

Comparison of short- and long-term effects of betaxolol and timolol on human retinal circulation.

PURPOSE: To determine the short- and long-term effects of betaxolol and timolol on human retinal circulation. METHODS: In a double-masked, randomised, placebo-controlled study we evaluated the effects of both a one-drop application and a twice-daily 2-week application of either topical 0.5% betaxolol hydrochloride or topical 0.5% timolol maleate on the retinal circulation in 12 healthy volunteers. Laser Doppler velocimetry was used to detect changes in the retinal venous blood flow. RESULTS: In both betaxolol- and timolol-treated eyes, intraocular pressure decreased significantly compared with baseline values after both 90 min and 2 weeks. In betaxolol-treated eyes, retinal blood flow did not change significantly after 90 min, but increased significantly (14 +/- 9%; p = 0.02) compared with baseline after 2 weeks. In timolol-treated eyes, retinal blood flow decreased significantly (18 +/- 5%: p = 0.04) compared with baseline after 90 min, and also decreased significantly (14 +/- 6%; p = 0.04) compared with baseline after 2 weeks. CONCLUSIONS: Retinal blood flow increases as a long-term effect of betaxolol and decreases as both a short- and long-term effects of timolol.

Adrenergic beta-Antagonists↗
PubMed1998

Hydrolysis of androgen receptor by cathepsin D: its biological significance in human prostate cancer.

OBJECTIVE: To elicit the biological role of a lysosomal protease, cathepsin D (CatD) in prostate cancer, by investigating its regulatory effect on the androgen receptor (AR) using human prostate cancer LNCaP cells and prostate tissue specimens. MATERIALS AND METHODS: Cell extracts were prepared from LNCaP or prostate specimens by cell lysis and tissue homogenization. Proteolytic assays were performed by incubating these extracts in acidic buffer (pH 3-4) at 37 degrees C. The resulting effects on AR and CatD were then analysed using Western immunoblots. RESULTS: The Western blots showed that AR was virtually hydrolysed with acid treatment, because endogenous CatD was activated; this activation only occurred at pH 3.2-3.5, but no specific acid appeared to be required. Further analyses suggested that CatD activation could be attributed to acid-induced autoproteolysis of mature CatD. Similar assays were also performed on prostate tissues, including normal and malignant specimens. These studies revealed that CatD-mediated AR hydrolysis was observed only in cancer specimens, while no such hydrolysis occurred in normal specimens. CONCLUSION: Endogenous CatD can hydrolyse AR, thereby possibly modulating AR function/metabolism in LNCaP cells, and in cancer specimens. CatD activity also appears to differ significantly between normal and malignant tissue. Thus, CatD may play a pivotal role as a growth modulator in androgen-dependent prostate cancer.

Blotting, Western↗
PubMed1998

Age-related cerebrovascular disease alters the symptomatic course of migraine.

Migraine headaches usually decrease in frequency and severity and often cease during advancing age. Occasionally, migraineurs report late-life migrainous accompaniments, i.e., auras without headache, particularly when typical migraine attacks terminate or diminish following major or minor strokes, at which time the auras may become atypical. Clinical observations such as these suggest that degenerative cerebrovascular changes accompanying aging may modify the course of migraine headaches particularly those with aura. To test this hypothesis, we quantitated age-related changes in cerebral vasodilator capacitance by measuring local cerebral blood flow utilizing xenon contrast computed tomography (CT) scanning before and after oral administration of the pharmacological cerebral vasodilator, acetazolamide (Diamox). Measurements were compared among 27 normal volunteers without headache (aged 24-94 years; mean age 61.1 +/- 17.6) and 37 carefully categorized groups of migraine patients (aged 27-83 years; mean age 59.4 +/- 12.4). The normals comprised Group A. Migraineurs were divided into two subgroups: Group B consisted of 27 migraineurs with and without aura who continued to suffer from incapacitating and frequent headaches and Group C consisted of 10 migraineurs who no longer suffered from severe and frequent headaches, two of whom still complained of atypical auras of the "late-life migrainous accompaniments" type. Cerebral vasodilator capacitance significantly declined with advancing age among normals and the two groups of migraineurs, confirming the development of age-related cerebrovascular diseases. Global CBF increases after Diamox in Group B (with persistent and severe migraine), were significantly greater compared with normals without headache, and with Group C consisting of migraineurs whose headaches had decreased, subsided, or become replaced by late-life migrainous accompaniments (Group C). Results establish that cerebrovasodilator capacitance declines with advancing age, probably due to progressive cerebral atherosclerosis, since these declines were accentuated by risk factors for stroke, particularly TIAs or documented lacunar infarcts by CT. Progressive impairments of cerebral vasodilator capacitance among migraineurs were associated with: (i) reductions in frequency and severity of migrainous cephalalgia and (ii) appearance of late-life migrainous accompaniments.

Adult↗
PubMed1998

Analysis of cathepsin D forms and their clinical implications in human prostate cancer.

PURPOSE: To assess cathepsin D (Cat.D) status in the prostate, we analyzed the different Cat.D forms in human prostate tissues using Western immunoblots. MATERIALS AND METHODS: Cell extracts were prepared from prostate tissues (n = 42) obtained from radical prostatectomy, adopting the tissue homogenization method. Expression of the different Cat.D forms was analyzed using Western blots. The catalytic activity of Cat.D was assayed by acid treatment, in which cell extracts were incubated in acidic buffer (pH 3 to 4) at 37C for 1 hour. RESULTS: Pathologically confirmed normal (NML), benign prostatic hyperplasia (BPH) and cancer (CAP) specimens all expressed Cat.D, but as two distinct forms. Both NML and BPH predominantly expressed an inactive procathepsin D (Pro.Cat.D), while CAP notably exhibited an active mature Cat.D. The assessment of Cat.D activity, using PSA (prostate specific antigen) as a physiological substrate, showed that such activity was consistently higher in CAP than in NML/BPH specimens. Further studies revealed that the mode of Cat.D activation in CAP specimens appeared to be primarily due to acid-induced autoproteolysis (self-degradation) of mature Cat.D. CONCLUSION: This study demonstrates that expression and activity of Cat.D varies among prostate specimens. A greater expression of mature Cat.D with a higher catalytic activity in CAP specimens is the most notable difference from NML/BPH. Therefore, the differential expression/activity of Cat.D forms may be a useful indicator for assessing prostate cancer status.

Blotting, Western↗
PubMed1998

Corneal and lens autofluorescence in young insulin-dependent diabetic patients.

To study the early ocular abnormalities in young diabetic patients, corneal and lens autofluorescence was measured by fluorophotometry in 30 eyes of 30 insulin-dependent diabetic patients without retinopathy. The lens [f(l)] and the corneal [f(c)] autofluorescence values in diabetic patients were significantly higher than in controls. In diabetic patients, f(l) was significantly correlated with the duration of diabetes, the f(c) was significantly correlated with the duration of diabetes and the indices of metabolic control, i.e. HbA1c and fructosamine. Our study demonstrated that young diabetic patients clearly had corneal and lens abnormalities before the appearance of overt diabetic retinopathy. The f(c) value might be a good indicator of metabolic control in diabetic patients.

Adolescent↗
PubMed1998

Risk factors for cerebral degenerative changes and dementia.

It is concluded that the most important determinants for cerebral neurodegenerative changes and cognitive decline during aging are neuronal shrinkage and/or loss, which are accelerated by certain risk factors: e.g. TIAs, hypertension, heart disease, hyperlipidemia, smoking, heavy alcohol consumption, male gender, low educational status, family history of cerebrovascular disease and absence of estrogen replacement therapy among women. Some of these risk factors are remediable by therapeutic interventions, including prevention of TIAs and medications that control hypertension, heart disease, hyperlipidemia and estrogen replacement in postmenopausal women, as well as abstention from abuse of tobacco and alcohol. Cerebral neurodegenerative changes measured by neuroimaging appear to be premorbid markers for depleted neuronal and synaptic reserves which predispose to the onset of dementias of both VAD and DAT types. Normal subjects at risk for cognitive decline include those with TIAs, hypertension and heart disease since these risk factors measurably accelerate cerebral atrophy, ventricular enlargement, leukoaraiosis, and decline in cortical perfusion.

Adult↗
PubMed1998

[Three adults with mild varicella and bronchial mucosal lesions].

We encountered three adults with varicella and bronchial mucosal lesions. Respiratory symptoms were minimal in all three. Chest X-ray films showed bilateral, diffuse, small, nodular shadows. Small, elevated lesions with white plaque's were seen on the bronchial mucosa bronchoscopically. Transbronchial lung biopsy, bronchial mucosal biopsy, and bronchoalveolar lavage were also done. The lung-biopsy specimen showed infiltration of lymphocytes into the interstitial space: VZV antigen was found by immunohistochemical staining of the lesion in one case. Analysis of bronchoalveolar lavage fluid revealed abnormally low CD 4/8 ratios in three cases. These findings suggest a high incidence of respiratory complications, especially bronchial lesions, despite the lack of respiratory symptoms, in adults with varicella.

Adult↗
PubMed1997

Experimental disc herniation: evaluation of the natural course.

STUDY DESIGN: Changes in L7 nerve root conduction velocity and changes in appearance on magnetic resonance study of the L6-L7 intervertebral disc in the dog were assessed for 2-6 months after an experimental disc herniation was performed. OBJECTIVES: To assess the time-related changes of nerve conduction velocity and magnetic resonance changes of the intervertebral discs. SUMMARY OF BACKGROUND DATA: It is known that nucleus pulposus may induce nerve root morphologic and functional changes when applied epidurally. However, it is not known whether such changes are reversible. METHODS: The spinal canal was opened by laminotomy of the upper part of the L7 lamina and the lower part of the L6 lamina on the left side. The L7 nerve root was gently retracted (sham) or the disc was punctured and injected with saline to produce herniation of the nucleus pulposus during the retraction time (herniation). After 1 day to 2 months, nerve root conduction velocity was determined by local electrical stimulation. Six dogs had the herniation or the sham procedure, and the L6-L7 disc was studied by magnetic resonance imaging at various times up to 6 months after the procedure. RESULTS: Decrease in nerve conduction velocity reached a maximum after 7 days and recovered to baseline level fully within 2 months. Although there was a clear reduction-recovery pattern, the difference in conduction velocity compared with that of the sham group was statistically significant after only 7 days. Disc degeneration started in the herniated discs within 7 days after the herniation procedure. However, none of the experimentally induced disc herniations were visualized by magnetic resonance imaging 7 days after the procedure. In no case was there subsequent nerve root compression. In one case, disc protrusion was visible 6 months after the herniation procedure. CONCLUSIONS: The results demonstrate for the first time that nucleus pulposus-induced nerve root injury reverses in 2 months and that it may be present without simultaneous nerve root compression, as confirmed by findings in magnetic resonance imaging. The previously described nucleus pulposus-induced nerve root changes may therefore be of clinical importance, and experimental studies of these mechanisms will probably be relevant for expanded understanding of the pathophysiologic mechanism behind sciatica that is caused by disc herniation.

Animals↗
PubMed1997

Normal human aging: factors contributing to cerebral atrophy.

Factors that accelerate rates of 'normal' age-related cerebral atrophic and degenerative changes are important because they may predispose to cognitive declines. To determine characteristic patterns of normal aging, risk factors were correlated with serial neurological-neuropsychological examinations, CT measures of progressive cerebral atrophy, local tissue hypodensities, or perfusional declines. Both cross-sectional and longitudinal designs were utilized. Ninety-four cognitively and neurologically normal aging volunteers, 15 with a history of transient ischemic attacks (TIAs), were followed for mean intervals of 3.0+/-2.1 years. Results indicated that: (1) after age 60, cerebral atrophy, polio- and leuko-araiosis doubled and cerebral perfusion decreased, with marked individual variations; (2) risk factors independently accelerating cerebral atrophy and cortico-subcortical perfusional declines included TIAs, hypertension, smoking, hyperlipidemia, excessive alcohol consumption and male gender; (3) progressive leuko-araiosis correlated directly with cortical atrophy and cortical perfusional declines. We posit that: (1) cerebral atrophy and degenerative changes result from neuronal shrinkage and/or loss, which are accelerated by TIAs, hypertension, smoking, hyperlipidemia, excessive alcohol consumption and male gender; (2) accelerated cerebral atrophic and degenerative changes identified by neuroimaging should be considered as markers for depleted neuronal synaptic reserves, which predispose to cognitive declines. Interventions available for controlling some of these risk factors include control of TIAs, hypertension, and hyperlipidemia, as well as tobacco and alcohol withdrawal.

Adult↗
PubMed1997

Juvenile amyotrophy of the distal upper extremity: pathologic findings of the dura mater and surgical management.

STUDY DESIGN: Five cases of juvenile amyotrophy of the distal upper extremity were reviewed retrospectively to elucidate the pathophysiology of spinal cord dysfunction and the results of surgical management. OBJECTIVES: To clarify the pathogenesis of juvenile amyotrophy of the distal upper extremity and to present the results of a new surgical treatment. SUMMARY OF BACKGROUND DATA: Hirayama first reported this disorder in 1959. It is characterized by juvenile onset, slow progression, and involvement of the unilateral distal upper extremity. Recently, compression of the cervical spinal cord during neck flexion was implicated as a possible etiology of the disorder, but the exact etiology is still unknown. The value of surgical treatment for patients with juvenile amyotrophy of the distal upper extremity has not been established. METHODS: The clinical and radiographic characteristics of five patients with juvenile amyotrophy of the distal upper extremity were examined. All five patients were treated surgically with duraplasty in combination with posterior spinal fusion. Dynamic and computed tomographic myelography were performed before and after surgery. Intraoperative ultrasonography and conductive spinal cord evoked potentials were recorded before and after duraplasty. The surgical results and the histology of the resected dura were studied. RESULTS: Myelograms taken with the neck in a neutral position showed that the spinal cord was flattened in all five patients. When the neck was flexed, the dura and the spinal cord were compressed further. Intraoperative ultrasonography during neck flexion revealed an anterior shift of the spinal cord and decreased spinal cord pulsation. Amplitude of the conductive spinal cord evoked potentials decreased with neck flexion but increased after dural incision. Histologically, the dura appeared abnormal in that it contained few elastic fibers without the normal wavy structure. CONCLUSIONS: Juvenile amyotrophy of the distal upper extremity was characterized by inelastic dura that constricts and compresses the cervical spinal cord when the neck is in either a neutral or a flexed position. Abnormal dura appeared to be the cause of juvenile amyotrophy of the distal upper extremity. Duraplasty with spinal fusion are proposed as treatments.

Adolescent↗
PubMed1997

Circulating intracellular adhesion molecule-1 concentrations following bronchial provocation in atopic asthma.

A house dust bronchial provocation test (BPT) was used to investigate the effect of allergen-induced airway inflammation and airway hyperresponsiveness (AHR) on the level of circulating intracellular adhesion molecule-1 (c-ICAM-1). The concentration of c-ICAM-1 was measured by the sandwich ELISA while the level of eosinophil cationic protein (ECP) in the sputum was determined by RIA. The parameter used for quantification of AHR was the minimum dose of methacholine (Mch) required to produce a fall in respiratory resistance and was expressed as log Dmin. Fourteen subjects with mild atopic asthma participated in this study. Ten patients (dual asthmatic response group; DAR group) developed a late asthmatic response (LAR) following an immediate asthmatic response (IAR). Four subjects (IAR alone group) exhibited only IAR following BPT. In both groups, the mean baseline concentration of c-ICAM-1 did not change 6 h after BPT (from 195.3+/-20.3 to 220.9+/-27.6 and from 215.5+/-23.5 to 231.3+/-30.5 ng/ml, respectively). However, BPT produced a significant increase in the mean concentration of c-ICAM-1 24 h later in the DAR group (257.3+/-41.14 ng/ml, p < 0.05), but not in the IAR alone group (225.5+/-18.1 ng/ml). BPT also increased ECP levels in the sputum from a baseline value 24 h after BPT in the DAR group (from 30.2+/-10.1 to 68.8+/-19.8 ng/ml; p<0.05), but not in the IAR alone group (from 28.1+/-8.3 to 43.3+/-23.7 ng/ml). There was a significant (p<0.05) correlation between c-ICAM-1-concentrations and sputum ECP levels 24 h after BPT in each group. Furthermore an inverse and significant (p<0.05) correlation was found between c-ICAM-1 concentrations and percent changes in log Dmin 24 h after BPT in each group. Our results suggest that increased concentrations of c-ICAM-1 after BPT may reflect the upregulated expression of airway ICAM-1 during allergen-induced airway inflammation. We propose that c-ICAM-1 is a useful marker for allergic inflammation, particularly that of eosinophilic infiltration into the airway, an essential feature of asthma.

Administration, Inhalation↗
PubMed1997

Classification, diagnosis and treatment of vascular dementia.

Vascular dementia (VAD) is considered to be the second most common cause of dementia in Europe and the US. In Asia and many developing countries, it is more common than dementia of the Alzheimer's type (DAT). VAD is the most preventable form of dementia associated with later life. The pathogenesis of VAD is multifactorial, and it represents a heterogeneous, not a homogeneous, clinical entity. Classification of VAD by pathogenesis is important for its prevention and treatment. Control of the risk factors for VAD reduces its incidence and stabilises or improves cognitive performance following stroke. Proper diagnostic evaluation of VAD requires: (i) a well defined quantitative assessment of the cognitive deficits present; (ii) assessment of risk factors for stroke; (iii) identification of cerebral vascular lesions by history, neurological examination and neuroimaging; (iv) exclusion of other causes of dementia; (v) establishment of a positive diagnosis of possible, probable or definite VAD versus DAT or mixed VAD/DAT; and (vi) identification of the temporal relationship between cognitive deficits and cerebral vascular lesions. VAD can be subdivided into 8 major types, as follows: (i) multi-infarct dementia secondary to large cerebral emboli [type 1]; (ii) strategically placed infarctions causing dementia [type 2]; (iii) multiple subcortical lacunar lesions secondary to atherosclerosis or degenerative arteriolar changes [type 3]; (iv) Binswanger's disease (arteriosclerotic subcortical leukoencephalopathy) [type 4]; (v) mixtures of types 1, 2 and 3 [type 5]; (vi) haemorrhagic lesions causing dementia [type 6]; (vii) subcortical dementia secondary to hereditary factors (type 7); and (viii) mixtures of DAT and VAD (type 8). Treatment is dictated by the pathogenetic subtype of VAD that is present.

Dementia, Vascular↗