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Biomedical subjects

Y Kuroda

Publications and source records attributed to Y Kuroda.

At least 109 records · Page 6Linked to original sources

[Tubulointerstitial nephritis in the case of acute renal failure from sepsis after a cat bite].

Acute tubulointerstitial nephritis is associated with a variety of causes, such as drug interaction, and infectious or immunological mechanisms. We describe a patient who suffered from sepsis, septic shock, disseminated intravascular coagulation(DIC), hepatic failure and renal failure after receiving a bite from her house cat. The causes of her acute renal failure were initially thought to be due to circulatory failure with hypotensive shock, decrease in renal blood flow with fibrin formation by DIC, or microangiopathy such as hemolitic uremic syndrome. However, the renal biopsy on the 60th hospital day indicated tubulointerstitial nephritis, which was recognized by the presence of patchy and focal mononuclear small cell infiltration with invasion to the tubular epithelium. We concluded that prolonged renal failure was caused by tubulointerstitial nephritis. The cause of tubulointerstitial nephritis was not identified. Tubulointerstitial nephritis should be taken into consideration when the recovery from acute renal failure is slow.

Acute Kidney Injury↗

Optimal duration of oral adjuvant chemotherapy with Carmofur in the colorectal cancer patients: the Kansai Carmofur Study Group trial III.

A multi-institutional study was performed to evaluate the appropriate duration of oral administration of Carmofur (1-hexylcarbamoyl-5-fluorouracil, HCFU), a 5-fluorouracil (5-FU) derivative, for postoperative adjuvant chemotherapy in patients with colorectal cancer undergoing curative operation. Patients were divided into two: i) short duration group receiving 6 months of HCFU administration and ii) long duration group receiving 1 year of the administration, using a centralized registration system. Among 364 patients entered in this study, 293 evaluable cases were analyzed to investigate the appropriate duration of adjuvant oral chemotherapy. No statistical differences were found in the cumulative 5-year disease-free or survival rates between the groups. However, the actual duration of oral HCFU administration differed in the patients of short and long duration groups from the protocol. Namely, more than 70% of the patients received a different duration of oral adjuvant chemotherapy in each of the groups. Therefore, apart from this division of two groups, correlation between the actual duration of oral HCFU administration and the prognosis was examined in these patients. As a result, it was suggested that oral adjuvant chemotherapy with HCFU would be effective in colon cancer patients when the duration of administration exceeded 330 days. In rectal cancer patients, however, adjuvant chemotherapy with HCFU alone was considered to be not sufficient to affect the prognosis.

Administration, Oral↗

[Proton magnetic resonance spectroscopy of the autistic brain].

To evaluate brain dysfunction in autism, proton magnetic resonance spectroscopy (1H-MRS) was performed for 29 autistic patients (5-15 y.o.) and 19 normal children (6-14 y.o.). We obtained magnetic resonance (MR) spectra of the left and right amygdaloid-hippocampal regions and the left cerebellar hemisphere with a STEAM sequence (TR = 5000 ms, TE = 18 ms). In addition to the evaluation of signal intensity ratios, the absolute concentration of three major metabolites (N-acetylaspartate [NAA], creatine/phosphocreatine [Cr] and choline-containing substances [Cho]) was quantified by an internal reference method using unsuppressed tissue water. Although no abnormal MR images were found in the three regions examined, the signal intensity and the concentration of NAA in the left amygdaloid-hippocampal region and the left cerebellar hemisphere were reduced significantly in autistic patients compared to normal children. We speculated that this decrease in NAA reflected neuronal loss, immaturity or hypofunction in these regions. The results of our study were in agreement with those of previous studies on autism, one by neuropathological methods and the other using a single photon emission computed tomography with 99mTc HMPAO. Disorders of the amygdaloid-hippocampal region and cerebellum are considered to play an important role in the characteristic cognitive and emotional dysfunction in autism. 1H-MRS is a valuable tool to clarify the pathophysiology of autism.

Adolescent↗

[Two cases of multiple liver metastases of colon cancer with systemic irinotecan and hepatic arterial injection of 5-FU].

We describe two patients with multiple liver metastases of colon cancer, who simultaneously received systemic irinotecan and hepatic arterial injection of 5-FU. In both cases, a notable partial response (more than 80%) in the hepatic metastases was observed. The patients could undergo chemotherapy without remarkable side-effects as out-patients. In the future, we shall perform a clinical study to evaluate the safety and dose limiting toxicity for the present combined chemotherapy.

Aged↗

[A case of Japanese encephalitis presenting with unilateral lesions in diffusion-weighted MRI].

We report the findings of diffusion-weighted MRI (DWI) taken serially in a patient with Japanese encephalitis (JE). The patient was a 43-year-old woman presenting with headache, high fever and consciousness disturbance. The diagnosis of JE was made based on more than fourfold elevation of serum complement fixation antibody titer for JE virus in the convalescent phase of illness. The DWI on the second day of illness (Day-2) disclosed high-signal intensity lesions in the left thalamus, substantia nigra and frontal lobe cortex. The signal intensity of these lesions on the DWI increased on Day-3 but gradually decreased thereafter and normalized on Day-28. The improvement of the DWI findings was paralleled with that of the consciousness level and the cell number and neuron specific enolase concentration in the CSF, suggesting that DWI is useful for evaluation of the disease activity in JE. The lesions in the brain suffering from Japanese encephalitis are usually bilateral and diffuse. To our knowledge, this is the first report of JE presenting with unilateral lesions on MRI, of which phathomechanism remains to be elucidated.

Adult↗

Glial cells contribute more to iron and aluminum accumulation but are more resistant to oxidative stress than neuronal cells.

Iron (Fe) and aluminum (Al) have been implicated in the pathogenesis of Alzheimer's disease (AD). In this study, we examined neuronal and glial cells to clarify which contributes most to metal accumulation after internalization through the transferrin-independent iron uptake (Tf-IU) systems in primary neuronal and glial predominant (NP and GP) cells from rat cerebral cortex, which affect the accumulation of transition metals in a variety of cultured cells. Al more significantly upregulated the Tf-IU activity in GP cells than in NP cells. GP cells were more resistant to Fe and Al exposure than NP cells. However, a chemiluminescence analysis specific for reactive oxygen species (ROS) showed that ROS levels in Fe- or Al-loaded NP cells were twice as high as in Fe- or Al-loaded GP cells. Northern blot analysis and gel retardation assay showed that the Al and Fe exposure taken up by the cells suppress Tf receptor mRNA expression to a greater extent in GP than NP cells, indicating that Al and Fe more markedly accumulate in glial than in neuronal cells. These results suggest that glial cells rather than neuronal cells contribute to the metal accumulation and are more resistant to oxidative stress caused by metals than neuronal cells. The present study may help to explain the pathogenesis of neurodegeneration in AD disorders caused by metal-generated oxidative stress.

Aluminum↗

Molecular mechanism of neurodegeneration induced by Alzheimer's beta-amyloid protein: channel formation and disruption of calcium homeostasis.

The etiology of Alzheimer's disease has been suggested to be linked to the neurodegeneration induced by beta-amyloid protein (AbetaP), however, the mechanism underlying the latter remains unknown. We have previously shown the direct incorporation of AbetaP into neuronal membranes of immortalized hypothalamic neurons (GT1-7 cells) associated with the formation of calcium-permeable pores, and the elevation of the intracellular calcium concentrations in the GT1-7 cells. Taking together our results and those of numerous other studies, we hypothesize that the disruption of calcium homeostasis by AbetaP-channels may be the molecular basis of the neurotoxicity of AbetaP, and the development of Alzheimer's disease. It is also proposed that the constituents of membrane lipids may play important roles in the process of this channel formation. Our hypothesis may also explain the mechanism of development of other 'conformational diseases', such as prion disease or type 2 diabetes mellitus, which share some common features with Alzheimer's disease.

Alzheimer Disease↗

Orientations and locations of local anesthetics benzocaine and butamben in phospholipid membranes as studied by 2H NMR spectroscopy.

This paper presents experimental evidence that an aromatic compound that has a quadrupole moment locates in a polar headgroup region in the lipid membranes, but not in a membrane interior hydrophobic region, and discusses correlation to the site of action of benzocaine and butamben on sodium channels. The 2H NMR spectra of benzocaine-d4, benzocaine-d5, butamben-d4, and butamben-d9 in the model membranes were observed. The 2H NMR spectra of perdeuterated palmitic acid and selectively deuterated palmitic acids at C2, C3, C5, C6, C9, or C10, which were inserted into the lipid membranes, were also observed. The phosphatidylserine (PS), phosphatidylcholine (PC), and liquid mixtures composed of PS, PC, and phosphatidylethanolamine (PE), which contain or do not contain cholesterol, were employed. A moment analysis was applied to the 2H NMR spectra of palmitic-d31 acid. An order parameter, S(CD), for each carbon segment was calculated from the observed quadruple splitting. We concluded that in the lipid mixture containing cholesterol, the aromatic rings of benzocaine and butamben locate around the glycerol moiety of the lipids and that when there exists no cholesterol, they locate a little more inside from the headgroup region, directing, in both cases, their amino groups upward (polar region) and the ethyl and butyl groups downward (hydrophobic region). These data cast a question on the site of action of the neutral local anesthetics in the sodium channels.

Anesthetics, Local↗

Clinical application of the two-layer (University of Wisconsin solution/perfluorochemical plus O2) method of pancreas preservation before transplantation.

BACKGROUND: The two-layer method [University of Wisconson solution (UW)/perfluorochemical plus O2] for pancreas preservation has been demonstrated to be superior to simple UW storage alone in the canine model. For the first time, we applied the two-layer method to clinical whole-pancreas transplantation. METHODS: Pancreases were placed in the two-layer method in 10 cases and UW alone in 44 cases before transplant. The mean cold ischemic time was 16.5 hr in the two-layer group versus 18.1 hr in the UW group (P=NS). We compared the condition of graft at the time of reperfusion, and then 3 months posttransplant graft function and complications. RESULTS: At the time of reperfusion, no grafts in the two-layer group were edematous, compared with 10(23.3%) of 43 in the UW group (P=0.18). Seven (70%) of 10 grafts in the two-layer group obtained the best overall quality score, compared with 24(57.1%) of 42 in the UW group (P=0.72). Nine (90%) of 10 recipients in the two-layer group became insulin-independent during hospitalization, compared with 31(70.5%) of 44 in the UW group (P=0.26). Time to insulin independence was no different between the two groups. No pancreas grafts preserved by the two-layer method suffered acute rejection. Conclusions. The two-layer preservation method is feasible in human clinical transplantation. It was at least equivalent and may be superior to UW alone in both morphologic and functional assessment of the transplanted pancreas.

Adenosine↗

The efficacy of conventional radiation therapy in the management of pituitary adenoma.

PURPOSE: To evaluate the efficacy of conventional radiotherapy for reducing tumor size and endocrine hypersecretion of pituitary adenomas. METHODS AND MATERIALS: We reviewed the records of 91 patients with pituitary adenoma, who were first treated between 1969 and 1994 and had been followed for more than 2 years (median, 8.2 years.) Of these patients, 86 had received postoperative radiotherapy, and 5 had received radiotherapy alone. The median total dose was 51 Gy. Clinical symptoms related to mass effects or endocrine hypersecretion were assessed. The efficacy of radiotherapy was evaluated before treatment and during the follow-up period (1-14 years; median, 3 years) by estimating tumor size on computed tomography or magnetic resonance imaging in 56 patients, as well as by endocrine testing in the 22 patients who had secreting adenomas. Local control rate, prognostic factors, and side effects were analyzed. RESULTS: Mass-effect symptoms improved in 72% and 79% of patients who had such symptoms due to nonsecreting adenomas and secreting adenomas, respectively. Symptoms of endocrine hypersecretion abated in 67% of patients who had such symptoms. Excessive hormone levels normalized in 74% of patients who showed endocrine hypersecretions. The greatest size reduction was seen 3 years after the completion of radiotherapy (24% CR, 62% PR, 12% NC, and 3% PD in nonsecreting adenomas, and 32% CR, 36% PR, 27% NC, and 5% PD in secreting adenomas). Three patients with secreting adenomas (2 with prolactinoma and 1 with Cushing's disease) showed a mismatch between reduction in tumor size and normalization of endocrine hypersecretion. The 10-year local control rates were 98%, 85%, 83%, and 67% for nonsecreting adenoma, growth-hormone-secreting adenoma, prolactinoma, and Cushing's disease, respectively. Univariate analyses showed that disease type and radiation field size were significant prognostic factors. Brain necrosis occurred in 1 patient who received a 60-Gy dose of irradiation. CONCLUSION: We conclude that conventional external radiotherapy with 50 Gy is safe and sufficient to control pituitary adenoma. Careful observation is required in the management of secreting adenomas because the effects on tumor size and endocrine hypersecretion may be mismatched in some secreting adenomas.

Adenoma↗

MCF-7 growth inhibition by ultraviolet radiation and 5-fluorouracil: the importance of treatment sequence.

Effective treatment of certain cancers with 5-fluorouracil (5-FU) and irradiation is well established; however, the most effective combination of these agents remains controversial. Although 5-FU has been identified as a radiosensitizer, the mechanism of action remains unknown. To assess the effect of combination, 5-FU and ultraviolet (UV), we constructed a new in vitro model with MCF-7 human breast cancer cells that measures growth inhibition and morphologic changes in nuclear argyrophilic nucleolar organizer regions (AgNORs). Cells were incubated in media containing 0, 50, 100 and 500 ng/ml 5-FU for 48 h, they were also exposed to UV irradiation of 90 J/m(2) at the beginning, middle, or end of the incubation period. The cells were incubated for an additional 48 h with 5-FU free media. A combined treatment with 5-FU and UV radiation demonstrated an additive inhibitory effect. The strongest growth inhibition was observed when UV exposure was at the beginning of the 5-FU treatment at 5-FU concentrations of 100 and 500 ng/ml. To elucidate the activity of 5-FU radiosensitization, we investigated the aggregation Pof AgNOR, which we previously established to reflect rRNA inhibition. A combined treatment with 5-FU and UV radiation accelerated the rate of AgNOR aggregation at 5-FU concentrations of 50 and 100 ng/ml. The timing of UV irradiation did not affect the rate of AgNOR aggregation. A combined treatment with 5-FU and UV radiation showed an additive inhibitory effect on MCF-7 cell growth that might be explained, in part, by rRNA inhibition.

Antimetabolites, Antineoplastic↗