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Biomedical subjects

M Fujishima

Publications and source records attributed to M Fujishima.

At least 91 records · Page 5Linked to original sources

Combination therapy using prednisolone and cyclophosphamide slows the progression of moderately advanced IgA nephropathy.

AIM: We retrospectively examined the effect of combination therapy using prednisolone (PSL) and cyclophosphamide (CPA) on the progression of IgA nephropathy (IgAN) in 45 patients with moderate to severe histological changes. PATIENTS AND METHODS: Patients were recruited from 129 consecutive patients with IgAN seen over 10 years based on semiquantitative histological grading. They were divided into two groups: PSL+CPA group (n = 26, male/female = 11/15, age 40+/-3 years (SEM)) or control group undergone conventional therapy with or without antiplatelet agents (n = 19, male/female = 10/9, age 41+/-3). In PSL+CPA group, PSL and CPA treatment commenced using a dose of 30 and 50 mg/day, respectively. PSL was reduced by 5 mg every month. RESULTS: The clinical parameters at the start of treatment such as age, gender, histological score, blood pressure, urinary protein excretion and serum creatinine concentration (SCr) were not different between the groups. The mean observation period in PSL+CPA group (3.3+/-0.3 years) was not different from the control group (4.0+/-0.7 years). In PSL+CPA group, urinary protein excretion, defined as the ratio of urinary protein to creatinine concentration (UP/UCr), significantly decreased from 3.9+/-0.4 to 1.3 +/-0.2 (p<0.01), whereas it remained high in the control group (3.8+/-0.7 to 2.7+/-0.8). The progression rate (PR), which was determined by the slope of the correlation between time after renal biopsy and reciprocal SCr, was significantly lower in PSL+CPA (0.054+/-0.014) than in the control group (0.172+/-0.032 dl/mg/year, p<0.001). Our results indicated that PSL+CPA combination therapy was effective in slowing the progression of moderately advanced IgAN. CONCLUSION: We suggest that the immunosuppressive treatment with CPA is sometimes necessary to preserve renal function in patients with histologically advanced IgAN.

Adolescent↗

Cerebral ischemia as a causative mechanism for rapid progression of brain atrophy in chronic hemodialysis patients.

BACKGROUND: It has been found that brain atrophy develops more rapidly in patients with end-stage renal failure after initiation of dialysis therapy. The present study was designed to analyze the relationship between brain atrophy and asymptomatic ischemic brain lesions. PATIENTS AND METHODS: Magnetic resonance imaging (MRI) was performed for the evaluation of brain atrophy and ischemic lesions. Brain atrophy was assessed by the ventricular-brain ratio (VBR), calculated as the ratio of the ventricular area to the whole brain area on the maximum MRI slice. The severity of periventricular hyperintensity (PVH) and the number of lacunae were also regarded as ischemic brain lesions. Fifty-five patients undergoing maintenance hemodialysis (HD) without clinically overt neurological signs and symptoms, with a mean age of 52 +/- 11 (SD) years and a mean HD duration of 7 +/- 6 (SD) years were subjected. VBR and its relationship to ischemic brain lesion data were compared to those in 35 non-HD patients (controls), with a mean age of 42 +/- 14 (SD) years. RESULTS: The VBR, the number of lacunae and the severity of PVH tended to increase with age in HD. The VBRs at all age groups were significantly higher in HD than in controls (7.0 vs 3.7% at the 4th decade, p < 0.05; 8.4 vs 5. 9% at the 5th decade, p < 0.05; 9.6 vs 5.4% at the 6th decade, p < 0.05; and 11.6 vs 6.3% at the 7th decade, p < 0.05). HD patients had significantly higher number of lacunae and had more advanced PVH than did controls. Both the number of lacunae and the severity of PVH were significantly correlated to VBR in HD. CONCLUSION: In conclusion, the rapid progression of brain atrophy was related to the asymptomatic ischemic brain lesions in our HD patients. Such data indicated that cerebral ischemia might be a causative mechanism of brain atrophy in chronic hemodialysis patients.

Atrophy↗

[A case of severe stenosis of bilateral distal vertebral artery successfully treated with anastomosis operation].

A 65-year-old male complained of loss of consciousness for several minutes, transient diplopia and dizziness. He had no neurological deficits nor abnormalities in MR imaging. However, flow velocity of bilateral vertebral artery on ultrasonography indicated severe stenosis of bilateral distal vertebral artery. Brain angiography revealed severe stenosis of bilateral distal vertebral artery as well as occlusion of right middle cerebral artery (MCA). Single photon emission CT (SPECT: ECD-RVR method with acetazolamide loading) showed decreased cerebral blood flow and poor perfusion reserve in bilateral cerebellar hemisphere and right MCA territory. Superficial temporal artery-superior cerebellar artery (STA-SCA) anastomosis was performed. The patient turned out to have no episodes of unconsciousness attack, transient diplopia and dizziness after operation. Cerebral blood flow (CBF) in the posterior circulation was also improved. Evaluating quantitative CBF measurement by means of ECD-RVR method was useful for evaluating CBF. In cases who have severe stenosis of bilateral distal vertebral artery with complaints of vertebrobasilar insufficiency, STA-SCA anastomosis may be one of the most effective treatments.

Aged↗

Ketoacidosis accompanied by epileptic seizures in a patient with diabetes mellitus and mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS).

We herein report a rare case of MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes) and diabetes mellitus with ketoacidosis. An 18-year-old female patient was diagnosed to have diabetes mellitus and insulin therapy was thereafter initiated. At 26 years of age, she was hospitalized for diabetic ketoacidosis, soon followed by a loss of consciousness, left-sided dysmetria, and ataxic speech. MELAS was diagnosed because of the presence of ragged red fibers in a muscle biopsy. At 33 years of age, she was admitted to our hospital because of ketoacidosis and partial status epilepticus. A blood gas examination revealed as follows; arterial pH, 6.88; bicarbonate, 2.1 mmol/l; base excess - 29.8 mmol/l. The serum level of glucose had also increased to 30 mmol/l. The serum levels of lactate and B-hydroxybutyrate were elevated to 11.4 mmol/l and 1,990 micromol/l, respectively. Ketoacidosis improved by fluid replacement and continuous intravenous insulin infusion. A brain MRI demonstrated hyperintensity areas on FLAIR images in the bilateral temporal lobes and the cerebellum. A proton MRS demonstrated the abnormal lactate accumulation in the bilateral temporal and occipital lobes. Since epileptic seizures are rare in patients with diabetic ketoacidosis, such seizures may indicate the existence of MELAS syndrome.

Adult↗

Optimal hematocrit for the maximum oxygen delivery to the brain with recombinant human erythropoietin in hemodialysis patients.

AIM: Although hematocrit (Ht) around 33 to 36% has been recommended, Ht of 30% is usually achieved as a target level during recombinant human erythropoietin (rHuEPO) therapy in the majority of hemodialysis (HD) patients. The present study aimed at estimating an optimal hematocrit (Ht) for the maximum oxygen delivery to the brain with rHuEPO. PATIENTS AND METHODS: Oxygen delivery was defined as a product of cerebral blood flow and arterial oxygen content (CaO2). The regional cerebral blood flow (rCBF) in each region of interest was measured by positron emission tomography and CaO2 was calculated from hemoglobin concentration, arterial oxygen saturation, and arterial oxygen tension before and after rHuEPO therapy (1,500 units, 3 times a week) in 5 HD patients (the mean age of 52 +/- 2 (SEM) years old and the mean HD duration of 98 +/- 21 months). RESULTS: Ht rose significantly from 21 +/- 1 to 31 +/- 1% (p < 0.001) after the 3-month rHuEPO treatment in association with a significant increase in CaO2 from 7.7 +/- 0.4 to 11.6 +/- 0.3 ml O2/100 ml (p < 0.01). Hemispheric rCBF decreased significantly from 40 +/- 3 to 32 +/- 1 ml/100 g/min (p < 0.02). In all data both before and after rHuEPO treatment, Ht inversely correlated with the hemispheric rCBF (y = 55.7 - 0.76x, where y is rCBF and x is Ht, r = 0.80, p < 0.01), and positively with CaO2 (y = 0.85 + 0.34x, where y is CaO2 and x is Ht, r = 0.95, p < 0.01). By using these correlations, the hemispheric oxygen delivery was expressed as a function of Ht, being y = 47.3 + 18.3x - 0.3 x2, where y is cerebral oxygen delivery and x is Ht. From this curve, Ht at the highest cerebral oxygen delivery in the hemisphere, i.e. an optimal Ht was found to be 35.2%. Above this level of Ht, the hemispheric cerebral oxygen delivery would rather decline. CONCLUSION: The present study indicated that Ht of about 35% is required for a better oxygen delivery to the brain metabolism during anemia correction with rHuEPO.

Anemia↗

Chronic intestinal pseudo-obstruction due to dialysis-related amyloid deposition in the propria muscularis in a hemodialysis patient.

Dialysis-related amyloidosis (DRA) is one of the most serious complications interfering with rehabilitation in dialysis patients. Here, we report a case of beta2-microglobulin (beta2M)-related amyloidosis, in which the patient developed a severe intestinal pseudo-obstruction. The patient was a 42-year-old male who had been undergoing hemodialysis for 13 years, and who had no history of osteoarticular involvement of DRA. The first symptoms of the disease were severe abdominal fullness and nausea after meals. The whole intestinal wall biopsy revealed massive amyloid deposition in the propria muscularis. The patient became malnourished and died of acute subendocardial infarction 3 years after the onset. An autopsical examination revealed a massive deposition of amyloid, which was positively stained with anti-beta2M antibody but not AA amyloid, predominantly in the gastrointestinal muscular layer, including the tongue, esophagus, stomach, small intestines, colon, and rectum. These results suggest that the gastrointestinal involvement of beta2M-related amyloidosis might occur during the course of hemodialysis treatment, and that this possibility should be considered if patients suffer from intestinal pseudo-obstruction without osteoarticular symptoms.

Adult↗

Depressed adenoma of the duodenum in patients with familial adenomatous polyposis: endoscopic and immunohistochemical features.

BACKGROUND: Depressed neoplastic lesions of the colorectum have been specified in patients with familial adenomatous polyposis (FAP). The aim of this study was to characterize endoscopic, histologic, and immunohistochemical features of depressed adenoma of the duodenum in patients with FAP. METHODS: Duodenoscopy was performed on 25 patients with FAP, and the neoplastic nonampullary lesions were classified as polypoid or depressed adenomas. The grade of dysplasia, the proliferative activity determined by Ki-67 labeling index (LI), and the grade of p53 expression were compared between polypoid and depressed neoplasia. RESULTS: Ten subjects had depressed nonampullary adenoma, whereas polypoid adenoma was found in the remaining 15 subjects. Moderate dysplasia was more frequent in depressed adenoma than in polypoid adenoma (70% vs. 27%, P = 0.04). Whereas p53 expression was not different between the two adenoma groups, the LI was significantly higher in depressed adenoma than in polypoid adenoma (59.7 +/- 9.5 vs. 47.5 +/- 10.7, P < 0.01). CONCLUSIONS: Depressed adenoma of the duodenum is a distinctive phenotype of duodenal neoplasm in patients with FAP. The high proliferative activity of depressed adenoma suggests that there may be a need to survey FAP patients with such lesions intensively.

Adenoma↗

Effects of antibiotics on the early infection process of a macronuclear endosymbiotic bacterium Holospora obtusa of Paramecium caudatum.

We examined the effects of antibiotics involved in bacterial DNA, RNA and protein synthesis and host protein synthesis on the early infection process of the bacterium Holospora obtusa, a macronucleus-specific symbiont of the ciliate Paramecium caudatum. Infection of the host macronucleus by the bacterium was not inhibited by mitomycin C, rifampicin and chloramphenicol. However, ingestion of the bacterium into the host digestive vacuoles and escape of the bacterium from the vacuoles to the host cytoplasm were significantly arrested with emetine. The results suggest that newly synthesized host proteins play an important role in the early infection process.

Animals↗

Subtypes of metabotropic glutamate receptors in the nucleus of the solitary tract of rats.

We have determined the role of subgroups of metabotropic glutamate receptors (mGluRs) in the nucleus of the solitary tract (NTS) of normotensive Wistar rats. Unilateral microinjection of (S)-3, 5-dihydroxyphenylglycine (3,5-DHPG), an agonist of group I mGluRs, into the NTS significantly decreased mean arterial pressure (MAP), heart rate (HR), and renal sympathetic nerve activity (RSNA) (-19. 4+/-2.6 mmHg, -16.4+/-5.1 beats/min, and -30.6+/-5.7% by 1 nmol). Microinjection of (R,S)-1-aminoindan-1,5-dicarboxylic acid (AIDA; 1 nmol), a putative antagonist of group I mGluRs, into the NTS caused transient decreases in MAP and RSNA, followed by sustained increases in MAP (+8.3+/-2.4 mmHg) and RSNA (+27.7+/-10.8%). Pretreatment with AIDA failed to prevent the cardiovascular and RSNA responses to microinjection of 3,5-DHPG. Unilateral microinjection of (S)-4-carboxy-3-hydroxyphenylglycine (4C3HPG), an agonist of group II mGluRs, into the NTS also significantly decreased MAP, HR, and RSNA, whose responses were not inhibited by pre-microinjection of (2S)-alpha-ethylglutamic acid (EGLU; 2 nmol), a putative antagonist of group II mGluRs. On the other hand, unilateral microinjection of L(+)-2-amino-4-phosphonobutyric acid (L-AP4), an agonist of group III mGluRs, into the NTS caused dose-related decreases in MAP (-8. 3+/-1.5 mmHg by 0.1 nmol and -45.1+/-3.4 mmHg by 0.3 nmol), HR, and RSNA (-21.3+/-3.9% by 0.1 nmol and -77.2+/-6.5% by 0.3 nmol), whose responses were suppressed by pre-microinjection of (R, S)-alpha-cyclopropyl-4-phosphonophenylglycine (CPPG; 0.3 nmol), an antagonist of group III mGluRs. These results suggest that all subgroups of mGluRs participate in cardiovascular and sympathetic regulations in the NTS of rats, and that endogenous group I mGluRs in the NTS may contribute to tonic cardiovascular and sympathetic regulations.

Animals↗

Sodium-potassium pump current in smooth muscle cells from mesenteric resistance arteries of the guinea-pig.

1. The Na+-K+ pump current was studied in smooth muscle cells from mesenteric resistance arteries of guinea-pigs by the use of the perforated patch-clamp technique in the presence of blockers for various ion channels and exchangers. 2. When the Na+ concentration in the pipette solution ([Na+]i) was 50 mM, an increase in the extracellular K+ concentration ([K+]o) from 0 to 10 mM caused an outward current. Both the removal of K+ from the bath solution and the application of 10 microM ouabain abolished this current. Thus, this K+-induced and ouabain-sensitive current was considered to be the Na+-K+ pump current. 3. The amplitude of the Na+-K+ pump current increased as the membrane potential was made more positive until around 0 mV, while the amplitude saturated at more positive potentials than 0 mV. 4. An increase in [K+]o or [Na+]i amplified the Na+-K+ pump current. For [K+]o, the binding constant (Kd) was 1.6+/-0.3 mM and the Hill coefficient (nH) was 1.1+/-0.2 (n = 6). For [Na+]i, Kd was 22+/-5 mM and nH was 1.7+/-0.5 (n = 4-19). 5. The presence of various monovalent cations other than Na+ in the bath solution also evoked the Na+-K+ pump current. The order of potency was K+ >= Rb+ > Cs+ >> Li+. 6. Ouabain inhibited the Na+-K+ pump current in a dose-dependent manner with a Kd of 0.35+/-0.03 microM and an nH of 1.2+/-0.1 (n = 6-8). 7. The Na+-K+ pump current increased as temperature increased. The temperature coefficient (Q10; 26-36 C) was 1.87 (n = 9). 8. In summary the present study characterized for the first time the Na+-K+ pump current in vascular smooth muscle cells by the use of the voltage-clamp method. The use of this method should provide essential information for Na+,K+-ATPase-mediated changes in the cell functions of vascular smooth muscle cells.

Animals↗