Biomedical subjects

H Kusaka

Publications and source records attributed to H Kusaka.

At least 55 records · Page 3Linked to original sources

PubMed1995

Antihypertensive effects of KW-3902, an adenosine A1-receptor antagonist, in Dahl salt-sensitive rats.

We determined the effects of KW-3902 (8-(noradamantan-3-yl)-1,3- dipropylxanthine), a novel adenosine A1-receptor antagonist, on the development of hypertension in Dahl salt-sensitive (Dahl-S) rats. KW-3902 (0.00017% w/w-0.017% w/w), fed with the diet, prevented the development of hypertension at 2-6 weeks in response to the high (8% w/w) NaCl diet. KW-3902 increased urine volume and sodium excretion and attenuated cardiac hypertrophy. In another series of the experiments employing the clearance method, KW-3902 (0.1 mg/kg, i.v.) increased urine volume, sodium excretion and lithium clearance in anesthetized Dahl-S rats. These results suggest that the antihypertensive effect of KW-3902 in Dahl-S rats is mediated via its natriuretic effect, the site of action being, at least partly, the proximal tubule. The adenosine A1-receptor antagonist may be effective for the treatment of salt-sensitive hypertension.

Animals↗

PubMed1995

Smoking promotes insidious and chronic farmer's lung disease, and deteriorates the clinical outcome.

Although the prevalence of serum precipitating antibodies for farmer's lung disease (FLD) is lower in smokers than in nonsmokers and FLD predominates in nonsmokers, the affects of smoking on the clinical course of the disease is not known. We compared the clinical findings and the prognosis between 12 smokers (SM-FLD) and 31 non-smokers with FLD (NS-FLD). There was no difference in age, sex, working years on farm, clinical symptoms, laboratory findings, radiographic findings, between the two groups. However, for the type of onset on the first visit for FLD, "acute single episode" type was less common, and "recurrent" and "insidious onset" types were more common in SM-FLD than in NS-FLD (8.3 vs 58.1, 91.7 vs 41.9%, respectively, p < 0.05). Although working status and mask wearing status were not significantly different between the two groups after the diagnosis of FLD, patients with symptoms and/or radiographic abnormalities of FLD of more than 6 months were found more frequently in SM-FLD than in NS-FLD (66.7 vs 19.4%, p < 0.005). And also SM-FLD had more recurrences of FLD than NS-FLD after the initial diagnosis of FLD (1.58 +/- 1.56 vs 0.47 +/- 1.07, p < 0.05). SM-FLD tended to have lower % VC than NS-FLD (73.6 +/- 7.4 vs 88.5 +/- 3.9%, respectively, p = 0.06). Regarding the prognosis, the 10-year survival rates were 70.7% in SM-FLD, and 91.5% in NS-FLD (p < 0.05). These results suggest that smoking may make FLD insidious and chronic, and deteriorates the clinical outcome.

Adolescent↗

PubMed1995

[A case of localized hypertrophic neuropathy in the sciatic nerve].

A 26-year-old male patient gradually developed muscular atrophy of the right lower leg over a two-year period. Neurological examination revealed absent Achilles tendon reflex and muscular atrophy of the right lower leg and right hamstring muscles. Conduction velocity of the F waves was delayed in the right posterior tibial nerve. A computerized tomography scan and magnetic resonance imaging revealed a mass lesion along the proximal segment of the right sciatic nerve. Exploration revealed a fusiformly swollen sciatic nerve. Histological examination showed that a swollen segment of the sciatic nerve was filled with onion-bulb formations of perineurial cells, consistent with the diagnosis of localized hypertrophic neuropathy. This condition should be added to several etiologies of monomelic amyotrophy. Electrophysiological studies and neuroimaging techniques were useful in obtaining differential diagnosis.

Adult↗

PubMed1995

[Acute leukoencephalopathy in Filipino women--report of two cases].

Two cases of acute leukoencephalopathy are reported. Both patients were Filipino women who had lived together in Japan for one month at the time of the onset. The first patient, 26 years old, suddenly developed right hemiplegia without fever. Small, high signal intensity lesions of the cerebral white matter were disseminated on T2-weighted magnetic resonance images. One week later, the patient became delirious, developed seizures, and lapsed into a comatose state with spastic quadriplegia. Corticosteroid was administered, resulting in improvement of consciousness levels. The patient was transferred to our hospital. Neurological examination disclosed severe pseudobulbar palsy and spastic quadriplegia without meningeal signs. Results of a cerebrospinal fluid examination were unremarkable. With magnetic resonance imaging, large irregularly-shaped lesions were seen in both centrum semiovale as high signal intensity areas on T2-weighted images and low signal intensity areas on T1-weighted images. Concentric structures in the lesions were particularly observed on T1-weighted images. One year later, the patient improved from a bedridden state to a wheel-chair bound state. The second patient, 23 years old, also developed right hemiplegia one week after the onset of the first case. MR imaging revealed small disseminated lesions in the cerebral white matter similar to those disclosed in the first case. From the onset, the patient was given corticosteroid, and experienced good recovery within one month. The clinical features, results of the laboratory examination, and MRI findings particularly in the first case suggest the diagnosis of so-called Baló's concentric sclerosis, despite the absence of pathological confirmation.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

PubMed1994

Synaptic pathology of spinal anterior horn cells in amyotrophic lateral sclerosis: an immunohistochemical study.

We have applied immunohistochemical techniques to study synaptic alterations of the spinal anterior horn in amyotrophic lateral sclerosis (ALS), and other disorders involving upper or lower motor neurons. A monoclonal antibody to synaptophysin was used. Spinal cord tissues from normal individuals served as controls. As compared to these, a decrease in synaptophysin immunoreactivity was evident in the neuropil in the spinal anterior horn of ALS patients. However, synaptophysin expression in the perikarya and dendrites of remaining normal-appearing neurons in these patients was not decreased and occasionally it was even higher than in control neurons. Similar results were obtained with specimens from patients with lower motor neuron disease. Synaptophysin immunoreactivity in the neuropil and perikarya of the cases with focal spinal cord lesions with bilateral descending tract degeneration was similar to normal controls. Our data suggest that the alterations in synaptophysin expression occurring in ALS are mainly associated with the loss of lower motor neurons, and that the occasional increased perikaryal expression may be due to the neuronal atrophy, compensatory accumulation or abnormal synaptic vesicle degradation.

Aged↗

PubMed1994

Colorectal tumours and pit pattern.

AIMS: To investigate the morphological and histopathological associations between an individual pit seen on stereomicroscopy or magnifying colonoscopy and an individual crypt seen in histological sections; and to examine these associations in colorectal tumours. METHODS: Fourteen thousand and twenty three cases were examined by colonoscope at Akita Red Cross Hospital. The surface mucosal pits of the lesions were observed using a magnifying endoscope in vivo and the pits of the extracted specimens were observed in vitro using a stereo microscope. Histological diagnoses were determined by light microscopy: the pit patterns in 100 glands were analysed. RESULTS: Pit pattern was classified into seven principal types: (1) normal round pit; (2) small round pit; (3) small asteroid pit; (4) large asteroid pit; (5) oval pit; (6) gyrus-like pit; and (7) non-pit. There was a correlation between pit pattern and the structure of the underlying crypt or gland. Furthermore, there was an association between pit pattern and the histology of the cells in the gland. Macroscopically, types 3, 4, 5, and 6 were common in protruding lesions. Type 2 was common in depressed lesions. The non-pit pattern was recognised in both. The depressed lesions had invaded the deeper layers more rapidly than protruding lesions. CONCLUSIONS: There were associations between individual pits and crypts. The branching carcinoma gland is thought to be the result of malignant transformation of the adenoma gland. The straight carcinoma gland is thought to result from the normal gland becoming malignant. The gland of the small round pit is thought to change from normal to the straight carcinoma gland via malignant transformation.

Adolescent↗

PubMed1994

Diuretic effects of KW-3902, a novel adenosine A1-receptor antagonist, in anesthetized dogs.

The effects of intravenous infusion of KW-3902 (8-(noradamantan-3-yl)-1,3-dipropylxanthine), a novel adenosine A1-receptor antagonist, on urine volume, urinary excretion of electrolytes and renal hemodynamics were examined in anesthetized dogs. KW-3902 at 10 and 30 micrograms/kg/min for 20 min inhibited the decline of renal blood flow induced by intrarenal arterial injection of adenosine (0.5-2.0 micrograms). KW-3902 at these doses produced significant increases in urine volume and sodium excretion with little change in potassium excretion. The diuretic effect of KW-3902 at 30 micrograms/kg/min for 20 min continued for longer than 1 h even after discontinuation of the KW-3902 infusion. KW-3902 did not affect creatinine clearance, renal blood flow, arterial blood pressure or heart rate. Furosemide at 10 micrograms/kg/min for 20 min brought about significant increases in urine volume and excretion of sodium and potassium. The diuresis and saliuresis induced by furosemide continued for only 40 min after discontinuation of the drug infusion. Trichlormethiazide at 3 micrograms/kg/min for 20 min also provoked increases in urine volume and sodium excretion, but did not affect potassium excretion. The diuretic and natriuretic effect of trichlormethiazide gradually disappeared after discontinuation of the drug infusion. The present study in anesthetized dogs suggests that KW-3902, an adenosine A1-receptor antagonist, produces diuresis and natriuresis but not kaliuresis and that the diuresis and natriuresis are caused in large part by the inhibition of sodium reabsorption at tubular sites.

Anesthesia↗

PubMed1994

Diuretic effects of KW-3902, a novel adenosine A1-receptor antagonist, in various models of acute renal failure in rats.

Using various models of acute renal failure (ARF) in rats, the diuretic effects of 8-(noradamantan-3-yl)-1,3-dipropylxanthine (KW-3902), a novel adenosine A1-receptor antagonist (0.01 and 0.1 mg/kg, p.o.), were determined and compared with those of furosemide (30 mg/kg, p.o.) and trichlormethiazide (TCM; 1 mg/kg, p.o.). In cisplatin-induced ARF rats, KW-3902 and TCM, but not furosemide, increased Na excretion. KW-3902 did not affect creatinine clearance (CCRE), while TCM decreased CCRE. In gentamicin-induced ARF rats, KW-3902 increased urine volume (UV) and Na excretion. In glycerol-induced oliguric ARF rats, KW-3902, but not furosemide or TCM, increased UV, Na and K excretion and tended to improve the depressed CCRE, suggesting that the improvement of renal hemodynamics might also contribute to the diuretic effect of KW-3902. In glycerol-induced polyuric ARF rats, only KW-3902 significantly increased UV and Na excretion. These results demonstrate that KW-3902 induces natriuretic effects in various models of ARF and that the effect of KW-3902 is more prominent than those of furosemide and TCM. The present results suggest that endogenous adenosine may be involved in various forms of ARF via adenosine A1-receptors.

Acute Kidney Injury↗

PubMed1994

Effects of KW-3902, a novel adenosine A1-receptor antagonist, on cephaloridine-induced acute renal failure in rats.

We investigated the possible renal protective effects of KW-3902 (8-(noradamantan-3-yl)-1,3-dipropylxanthine), a selective and potent adenosine A1-receptor antagonist, against cephaloridine (CER)-induced acute renal failure (ARF) in rats. ARF was induced by intravenous injection of CER at a dose of 600 mg/kg body weight. KW-3902 at doses higher than 0.01 mg/kg (p.o.) dose-dependently attenuated the decrease of creatinine clearance and the increase of proteinuria in rats with CER-induced ARF. In contrast, furosemide and trichlormethiazide (TCM) increased urinary protein and aggravated the serum parameters. These results suggest that KW-3902 has some advantages over furosemide and TCM when used in combination with CER. In the diuretic study in the rats with established ARF induced by CER, KW-3902, furosemide and TCM caused a significant increase in sodium excretion, whereas acetazolamide was ineffective. These results suggest that the proximal tubule is functionally damaged in rats with CER-induced ARF, in accord with the histological observation demonstrating the degeneration of the proximal tubule. From the fact that KW-3902 induces diuretic action even in CER-induced ARF, it is suggested that KW-3902 acts, directly or indirectly, on the proximal tubule or other tubular sites in the kidney, resulting in the diuretic effect.

Acute Kidney Injury↗

PubMed1994

Protective effects of KW-3902, a novel adenosine A1-receptor antagonist, against gentamicin-induced acute renal failure in rats.

We investigated the possible renal protective effects of KW-3902 (8-(noradamantan-3-yl)-1,3-dipropylxanthine), an adenosine A1-receptor antagonist, against gentamicin (GM)-induced acute renal failure (ARF) in rats. ARF was induced by subcutaneous injection of GM at 80 mg/kg/day for 12 days. KW-3902 (0.001-0.1 mg/kg, p.o., twice daily) attenuated the increases of serum creatinine and urea nitrogen and the decrease of creatinine clearance in rats treated with GM. In contrast, furosemide and trichlormethiazide aggravated the GM-induced nephrotoxicity. These results suggest that KW-3902 can ameliorate the GM-induced ARF and that endogenous adenosine may be involved in GM-induced ARF via the adenosine A1-receptor.

Acute Kidney Injury↗

PubMed1994

Effects of benidipine on renal function in anesthetized spontaneously hypertensive rats.

Effects of benidipine on urine volume, excretion of electrolytes and renal hemodynamics were investigated in anesthetized spontaneously hypertensive rats (SHR). Benidipine at 3 and 10 micrograms/kg (i.v.) significantly increased urine volume, sodium (Na) and potassium (K) excretion with no change of creatinine clearance (CCRE). The increase in K excretion was relatively slight when compared with that in Na excretion. In another series of experiments, the tubular sites of action of benidipine were determined by the lithium clearance (CLi) technique and the stop-flow method. Benidipine at 3 micrograms/kg (i.v.) increased CLi, decreased creatinine concentration and increased Na concentration in the stop-flow urine from the distal nephron. These results suggest that benidipine produces diuresis and natriuresis by the inhibition of water and Na reabsorption at both the proximal tubule and the distal nephron. Benidipine increased p-aminohippuric acid clearance, but not CCRE, at doses of 3 and 10 micrograms/kg (i.v.), suggesting that benidipine dilates the glomerular efferent arteriole as well as the afferent arteriole. It is, therefore, expected that benidipine does not cause intraglomerular hypertension and has a beneficial effect in progressive renal disease.

Anesthesia↗

PubMed1994

[A family with hereditary neuropathy with liability to pressure palsies--clinical, electrophysiological, pathological study and DNA analysis].

Hereditary neuropathy with liability to pressure palsies (HNPP) is an autosomal dominant disease that causes episodes of recurrent mononeuropathies following minor trauma or pressure. It was recently reported that deletion of the peripheral myelin protein-22 (PMP-22) gene was associated with HNPP in three unrelated American pedigrees and one Dutch pedigree, but not in another Dutch pedigree. We tested a Japanese family with HNPP for PMP-22 gene deletion. HNPP diagnosis was established by a history of recurrent mononeuropathies following moderate compression, delayed distal latencies and F-wave latencies, and the characteristic focal thickening of the myelin sheath ("tomacula") in sural nerves. Genomic DNA of the HNPP patients was extracted from peripheral blood lymphocytes. The DNA was cut by the restriction endonuclease BamHI, separated by electrophoresis and the fragments hybridized with probes for PMP-22 cDNA and human muscle specific phosphoglycerate mutase (PGAM) cDNA (used as internal control). The intensity of the autoradiographs of patients was measured densitometrically and compared to that of normal controls. Our analysis revealed that the PMP-22 and PGAM autoradiograph intensity ratio in the specimens of the HNPP patients was 60% of that of control individuals, thus suggesting that the patients only had a single copy of the PMP-22 gene. From these data we conclude that the PMP-22 gene also was deleted in the Japanese family with HNPP.

DNA↗

PubMed1994

[A case of bilateral medial longitudinal fasciculus (MLF) syndrome associated with rotatory nystagmus].

We report a patient with bilateral MLF syndrome associated with rotatory nystagmus. The patient was a 33-year-old female, admitted to our hospital because of sudden onset of diplopia. The adduction of both eyes were markedly disturbed on lateral gaze, but convergence was relatively spared. Excyclorotatory nystagmus was observed in the right eye on the rightward gaze, and gaze-directional horizontal gaze nystagmus was observed in the left eye on the leftward gaze. No other neurological abnormality was pointed out. T2-weighted magnetic resonance imaging revealed a high intensity lesion in the pontine tegmentum. The lesion was located at the mid-pontine level. Rotatory nystagmus has been rarely observed in the patients with MLF syndrome, and previous authors postulated a lesion in the MLF above the level of the abducens nucleus and below the level of the trochlear nucleus. In our patient we demonstrated a lesion in the hypothesized location on magnetic resonance imaging and provided a supportive anatomical evidence.

Adult↗

PubMed1993

Ubiquitin-positive inclusion in anterior horn cells in subgroups of motor neuron diseases: a comparative study of adult-onset amyotrophic lateral sclerosis, juvenile amyotrophic lateral sclerosis and Werdnig-Hoffmann disease.

This report concerns the expression of ubiquitin in anterior horn cells of various subgroups of adult and infantile motor neuron disease (MNDs); immunohistochemical techniques were employed. Ubiquitin-positive skein-like inclusions (SLIs) were found in all cases of adult-onset amyotrophic lateral sclerosis (ALS), including 16 cases with sporadic ALS, two cases of familial ALS with posterior column degeneration and Lewy body-like hyaline inclusions (LBHIs), two sporadic ALS cases with LBHIs, and three cases of sporadic ALS with dementia. SLIs were not found in anterior horn cells of 5 cases with Werdnig-Hoffmann disease (WHD). However, granular ubiquitin-positive deposits were seen in ballooned neurons of WHD patients. No ubiquitinated materials were found in the perikarya of two sporadic juvenile ALS patients with basophilic inclusions (BIs), but granular ubiquitin-immunoreactive deposits were occasionally observed in the BIs. These results suggest that ubiquitin-positive SLIs are characteristic features of various forms of adult-onset ALS and that aggregated ubiquitinated granules are characteristic of ballooned neurons of WHD. Ubiquitinated structures and their distribution patterns may reflect degenerative processes of anterior horn cells, and may be useful for classifying subgroups of motor neuron diseases.

Adult↗

PubMed1993

Effects of repeated administration of KW-3902, a novel adenosine A1-receptor antagonist, on its pharmacological actions.

Effects of repeated administration of KW-3902, a novel adenosine A1-receptor antagonist, on its pharmacological actions were studied with regards to: 1) in vivo adenosine A1-antagonism, 2) diuretic effects and 3) renal protective effects against glycerol-induced acute renal failure (ARF). After repeated oral administration of KW-3902 (0.1 mg/kg/day) for 24 days, neither enhancement of the sensitivity to 5'-N-ethylcarboxamidoadenosine (NECA) nor reduction of the inhibitory effect of KW-3902 on the NECA-induced bradycardic response were observed. After repeated oral administration of KW-3902 (0.01 and 0.1 mg/kg/day) for 20 days, the diuretic effects of KW-3902 did not change. Renal protective effects against glycerol-induced ARF were not reduced by repeated oral administration of KW-3902 (0.01 and 0.1 mg/kg/day) for 23 days. These results suggest that repeated oral administration of KW-3902 has no effect on its pharmacological actions. Additionally, changes in serum parameters, which occurred after repeated administration of furosemide or trichlormethiazide, were minimal after repeated oral administration of KW-3902 (0.001-1 mg/kg/day) for 27 days. From these results, KW-3902 proved to be a diuretic which has renal protective effects with less side effects.

Acute Kidney Injury↗

PubMed1993

Two-year follow up on the protective value of dust masks against farmer's lung disease.

Some advocate moving away from the farm environment for farmers affected with farmer's lung disease (FLD), but most affected farmers still live on farms. In this study, we evaluated the practicality of dust masks and their effectiveness in prevention of FLD. The dust masks we chose were practically used and no new severe episodes of FLD developed in 20 of 21 farmers with FLD using the masks during a 2-year period. When the farmers took off the dust masks in a farming environmental provocation test, statistically significant reductions in FVC (mean 3.43 to 3.351, p < 0.01), DLco (mean 19.6 to 18.2 ml/torr/min, p < 0.01), and DL/VA (mean 5.1 to 4.8 (x10(-3)) 1/torr/min, p < 0.01) were observed several hours after exposure. These findings suggest that the dust masks were used practically during routine dairy farming and were effective in protection against FLD.

Adult↗

PubMed1993

[A comparative immunohistochemical study of ubiquitin-positive skein-like inclusions in anterior horn neurons in subgroups of adult-onset motor neuron diseases].

This study investigated the expression of ubiquitin in anterior horn cells of various subgroups of adult-onset motor neuron diseases (MNDs). Ubiquitin-positive skein-like inclusions (SLIs) were found in all 11 cases of sporadic amyotrophic lateral sclerosis (ALS) patients, two patients with lower MND, 3 sporadic cases of ALS with dementia, 3 sporadic ALS cases with long-term use of respirators, and two cases of sporadic ALS with Lewy body-like hyaline inclusions. This result suggests that a similar pathomechanism is involved in the degeneration of the lower motor neurons in these subgroups. SLIs were not detected in two cases of adult-onset MND with basophilic inclusions. This may indicate that adult-onset MND with basophilic inclusions is a distinct nosological entity of classical ALS and some relationship to juvenile ALS with basophilic inclusions is suggested.

Age of Onset↗

PubMed1993

[Angiotropic lymphoma presenting with subacute dementia: treatment with combination chemotherapy (CHOP) based on antemortem diagnosis--a case report].

We report a 64-year-old male with angiotropic lymphoma. He developed subacute dementia with right hemiparesis. Laboratory abnormalities included elevated serum lactic dehydrogenase (LDH) (715 U/l) erythrocyte sedimentation rate (38 mm/hr) and CSF protein (90 mg/dl). Precontrast MR imaging of the brain demonstrated lesions involving the left internal capsule, subcortical white matter in the right frontal lobe and splenium within the atrophic corpus callosum. A brain biopsy revealed intravascular lymphoid cells, strongly suggestive of angiotropic lymphoma. By combination chemotherapy (CHOP), serum LDH and CSF protein normalized through the patient remained demented. He died of bronchopneumonia about 2 years and 5 months after the onset. Coronal sections of the brain showed infarct in the left internal capsule as well as markedly thin corpus callosum with necrotic lesions involving both the genu and splenium. Microscopic examination showed many small vessels occluded by lymphoma cells (B-lymphocyte) predominantly in the corpus callosum, cerebral white matter, thalamus, midbrain, medulla oblongata, thoracic and lumbar segments of the spinal cord. By combination chemotherapy, our patient survived longer than most of previous patients with angiotropic lymphoma. An early diagnosis and subsequent combination chemotherapy may improve neurological manifestations, and make possible longer survival in angiotropic lymphoma.

Antineoplastic Combined Chemotherapy Protocols↗