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Biomedical subjects

Akira Kawashima

Publications and source records attributed to Akira Kawashima.

At least 19 recordsLinked to original sources
PubMed2007

Renal involvement in patients with autoimmune pancreatitis: CT and MR imaging findings.

PURPOSE: To retrospectively evaluate computed tomographic (CT) and magnetic resonance (MR) imaging renal findings at clinical presentation, during treatment, and at follow-up in patients with autoimmune pancreatitis (AIP). MATERIALS AND METHODS: This HIPAA-compliant study received institutional review board approval. All patients included had previously consented to the use of their medical records for the purpose of research. Forty-five patients (38 male and seven female patients; mean age, 64 years) with diagnosis of AIP were included. Forty patients underwent CT or MR imaging at clinical presentation; 33 patients (including five without imaging at presentation) underwent follow-up. CT and MR images were reviewed in consensus by two radiologists for the presence of renal involvement. Various features were evaluated. Clinical characteristics at presentation were compared between patients with and patients without renal involvement. RESULTS: Of the 40 patients who underwent imaging at presentation, 14 (35%) had renal involvement (12 with parenchymal involvement and five with extraparenchymal involvement). Renal parenchymal lesions showed decreased enhancement and appeared as small peripheral cortical nodules, round or wedge-shaped lesions, or diffuse patchy involvement. Thirteen patients with renal involvement at presentation underwent a follow-up study. Renal lesions in 10 patients regressed (in nine, after steroid treatment) but progressed in three patients without steroid treatment. Renal lesions were found in two other patients during follow-up. No significant difference in the clinical characteristics was found between patients with and patients without renal involvement. CONCLUSION: Renal involvement in patients with AIP is relatively common and predominantly involves the cortex of the kidney. The lesions improve after steroid treatment but can progress without steroid treatment.

Adolescent↗
PubMed2006

Binding mode of novel 1-substituted quinazoline derivatives to poly(ADP-ribose) polymerase-catalytic domain, revealed by X-ray crystal structure analysis of complexes.

In order to clarify the role of the 1-substituent of quinazoline derivatives in their inhibitory activity against poly(ADP-ribose) polymerase (PARP), two novel inhibitors, 1 [8-hydroxy-1-(3-morpholinopropyl)-quinazoline-2,4(1H,3H)-dione] and 2 [8-hydroxy-1-(3-phenoxypropyl)-quinazoline-2,4(1H,3H)-dione], were synthesized and subjected to X-ray crystal analysis in complex with the PARP C-terminal catalytic domain (PARP-CD), which requires NAD+ coenzyme for biological function. The nicotinamide-mimicking part of the quinazoline skeleton of 1 and 2 were both located at the nicotinamide subsite of the NAD+-binding pocket in the same manner as previously reported inhibitors: three hydrogen bonds [(Gly-863)NH-O12, (Gly-863)O-HN3 and (Ser-904)O(gamma)-O12] and stacking interaction between the Tyr-907 phenol and the quinazoline ring. On the other hand, the N-morpholinoprop-3-yl moiety introduced at the 1-position of the quinazoline ring in 1 bridged the large gap between the donor site and the acceptor site through a (Met-890)NH-O20(morpholine) hydrogen bond, where the donor and the acceptor sites are classified as the binding sites of NAD+ and the ADP moiety of the poly(ADP-ribose) chain, respectively. In contrast, the N-phenoxyprop-3-yl moiety in 2 formed hydrophobic interactions close to the adenosine-binding site of NAD+, unlike the hydrogen bond such as in 1. As the inhibitory activities of 1 and 2 for PARP were much more potent than those of the unsubstituted nicotinamide analogues, these results suggest that the occupation of the proximal region of the ADP phosphate-and adenosine-binding subsite of the donor site or that of the gap between the donor and the acceptor site by the 1-substituent of quinazoline may increase the inhibitory activity considerably. The nearly equal inhibitory activities of 1 and 2, despite of their different binding modes at the active site, indicate that this 1-substituent is promising in improving the bioavailability of the inhibitor without compromising its inhibitory activity.

Animals↗
PubMed2006

Synthesis of 2-methyl 16-membered macrolide derived from tylosin.

To improve the metabolic stability of a 16-membered macrolide, 2-methylated derivatives of desmycosin were synthesized. Among these derivatives, 2beta-methyldesmycosin retained antibacterial activity and showed improved stability in rat serum compared to desmycosin.

Animals↗
PubMed2006

Relationship between AUC of 5'-DFUR and toxicity of capecitabine, fluoropyrimidine carbamate analogs, and 5'-DFUR in monkeys, mice, and rats.

Capecitabine is an oral fluoropyrimidine carbamate which is converted to 5-fluorouracil (5-FU) via 3 enzymatic step to 5'-deoxy-5-fluorocytidine (5'-DFCR), 5'-deoxy-5-fluorouridine (5'-DFUR), and finally 5-FU. We performed 4-week toxicity studies of capecitabine (N(4)-pentyloxycarbonyl-5'-deoxy-5-fluorouridine), galocitabine (trimethoxybenzyl-5'-deoxy-5-fluorocytidine), 4 different fluoropyrimidine carbamate analogs (R=butyl, isopentyl, propyl, or phenethyl), and 5'-DFUR in cynomolgus monkeys with toxicokinetic measurements of intact molecules, 5'-DFCR, and 5'-DFUR. Four-week toxicity data for capecitabine in rats and mice were also obtained for comparison. Capecitabine, galocitabine, butyl, and isopentyl analogs showed similar toxicities in hematopoietic and intestinal organs at 1.0 mmol/kg and the AUCs of 5'-DFUR were approximately 40 to 60 microg*hr/ml. These compounds showed slight toxicity at 0.5 mmol/kg and no toxicity at 0.1 mmol/kg, and AUCs of 5'-DFUR were approximately 30 and 5 microg*hr/ml, respectively. Propyl and phenethyl analogs showed slight toxicity at 1.0 mmol/kg and no toxicity at 0.5 mmol/kg, and AUCs of 5'-DFUR were approximately 30 and 10 microg*hr/ml, respectively. On the other hand, severe and slight-to-moderate toxicity was observed at 0.5 and 0.25 mmol/kg in 5'-DFUR-treated monkeys and AUCs of 5'DFUR were 35.6 and 5.2 microg*hr/ml, respectively. In mice and rats, the toxicity of capecitabine was less than in monkeys relative to dose, but 5'-DFUR AUCs were almost the same. In conclusion, 5'-DFUR AUC correlated with toxicity following oral administration of capecitabine and its analogs in monkeys, mice, and rats, although this relationship is not seen in humans. Capecitabine was less toxic in monkeys than oral 5'-DFUR according to dose (mmol/kg) and 5'-DFUR AUC.

Animals↗
PubMed2006

Use of hot water bottles can improve lymphocytopenia.

We observed that patients with lymphocytopenia have a cold external body temperature-especially the abdomen, hips and extremities-as recognized by palpation. Such patients were recommended to use a hot water bottle especially for cold extremities for the purpose of improving "chill". Six cases of lymphocytopenia diagnosed by previous medical doctors within two weeks before consulting our clinic are described in this study. The patients warmed their trunks and extremities by hot water bottles for as long as possible not only while sleeping but also during the daytime. There was no remarkable change in leukocyte count, but granulocytes significantly decreased in number (from 6,716 +/- 4,032 to 5,467 +/- 2,660) (p=0.013), and lymphocytes significantly increased from 718 +/- 211 to 1,845 +/- 406 (p=0.0017). It is important for clinicians to recognize that such an easy method can improve lymphocytopenia.

Adult↗
PubMed2005

In situ partial nephrectomy and tumor thrombectomy for renal cell carcinoma with level II vena cava extension in a solitary kidney.

The presence of renal cell carcinoma within a solitary kidney and vena cava extension presents complex management and surgical decisions for the treating urologist. To the best of our knowledge, we present the first case of partial nephrectomy and level II caval thrombectomy within a solitary kidney. Accessory renal veins were identified preoperatively using a three-dimensional, multidetector row computed tomography scan and preserved intraoperatively, allowing complete oncologic resection without compromising renal function.

Adult↗
PubMed2005

Cisplatin-induced cytotoxicity in BSO-exposed renal proximal tubular epithelial cells: sex, age, and species.

BACKGROUND: Cisplatin (CP)-induced kidney damage and effects of DL-buthionine-(S,R)-sulfoximine (BSO) on it are species- and age-different. It remains unclear whether CP-induced cytotoxicity in renal proximal tubular epithelial cells (RTEC), the main target cells of CP, is also species- and age-different; and whether CP-induced cytotoxicity varies with the difference in age and species, if any, is one of the questions. In the present study, the effects of BSO on CP-induced cytotoxicity in primary cultures of RTEC isolated from monkeys and different age and sex rats were studied. METHODS: The RTEC were isolated from 3-week-old, 2-month-old, or 5-month-old rats, and 6-8 year-old monkeys. After subculturing, RTEC was inoculated into type I collagen-coated 96-well culture plates; after preincubation, 40 microM BSO was added, 16 hours later, varying concentrations of CP were added. At that time, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assays were performed to test cell viability. RESULTS: The concentrations of CP that inhibited 50% cell growth (IC50) of RTEC from rats and monkeys were 1.11 and 3.03 mM at 8 hours, and 0.51 and 1.24 mM at 24 hours, respectively. The BSO made the IC50s of RTEC from rats and monkeys lower, down to 0.07 and 0.48 mM at 8 hours, and 0.02 and 0.11 mM at 24 hours, respectively. The IC50s of RTEC from different sex and age rats were almost same. CONCLUSION: These results suggested that CP-induced cytotoxicity was concentration- and time-dependent, with species-dependent differences, rat RTEC were more susceptible to CP than monkey RTEC, rat RTEC were more dependent on glutathione (GSH) during the stress state were than monkey cells; CP-induced cytotoxicity was without sex- and age-dependent differences in rat RTEC.

Animals↗
PubMed2005

Three-dimensional CT virtual endoscopy in the detection of simulated tumors in a novel phantom bladder and ureter model.

BACKGROUND AND PURPOSE: Cystoscopy and ureteroscopy have limitations in the evaluation for urothelial tumors, and both are invasive. We studied the utility of three-dimensional (3D) CT virtual endoscopy in phantom models. MATERIALS AND METHODS: A phantom pelvis was constructed of Plexiglas, porcine pelvic bones, and processed animal fat and scanned at various table speeds in a four detector-row CT machine for ability to detect "tumors" of Solidwater plastic polymer. Images were reconstructed at slice thicknesses of 2.5 to 5.0 mm and reconstructed in 3D for evaluation by two radiologists with no knowledge of the scanning parameters or tumor location. Similar studies were performed with a ureter model. RESULTS: With 5-mm slices, the sensitivity for bladder tumors ranged from 67% for 2-mm tumors to 100% for 4-mm tumors, with 12 false-positive findings. The overall sensitivity was 86% with 3.75-mm slices with one false positive, and with 2.5-mm slices, the sensitivity was 93%, again with one false positive. For the ureteral tumors, the overall sensitivities and numbers of false positives were 88.9% and eight with 5.0-mm collimation, 88.9% and four with 3.75-mm collimation, and 100% and three with 2.5-mm collimation. The effective radiation dose for all studies was equivalent to that of a standard abdomen/pelvis scan. CONCLUSIONS: Although virtual endoscopy traditionally has had difficulty detecting tumors <5 mm, the multidetector-row CT protocols used in this study could detect most lesions smaller than this. The scan also depicts the other tissues of the pelvis, which is valuable for staging. The 3D images were produced using data from the CT urogram parameters standard at our institution.

Animals↗
PubMed2004

Applications of positron emission tomography imaging, intraoperative ultrasonography, magnetic resonance imaging, and angiography in the evaluation of renal masses.

Most renal masses and cysts are adequately characterized by ultrasonography or computerized tomography. Occasionally, further diagnostic evaluation is needed. Magnetic resonance imaging has emerged as the premier study to evaluate suspected tumor thrombus and to plan the operative technique in challenging cases. Intraoperative ultrasonography is a valuable real-time imaging modality for delineating tumor extent and margins during nephron-sparing surgery and in evaluating the presence of synchronous multifocality. Additionally, localized central renal tumors can be treated with ultrasonography-guided radiofrequency ablation. Positron emission tomography has little use in the diagnostic evaluation of renal masses, but may be useful in staging equivocal cases and in evaluating suspected recurrence or metastases in patients after nephrectomy for renal cell carcinoma.

Humans↗
PubMed2004

Effects of BSO and L-cysteine on drug-induced cytotoxicity in primary cell cultures: drug-, cell type-, and species-specific difference.

The effects of DL-buthionine-(S,R)-sulfoximine(BSO) and L-cysteine(CYS) on cytotoxicity induced by cisplatin(CP) and diclofenac(DIC) in primary cell cultures of hepatocytes and renal tubular epithelial cells(RTEC) isolated from rats or monkeys were studied. Hepatocytes and RTEC were inoculated into collagen-coated 96-well culture plates. After preincubation, a series of concentrations of CP or DIC were added, and 16 h and 4 h prior to CP and DIC, 40 microM BSO and 5 mM CYS were added, respectively. MTT assays were performed to evaluate cytotoxicity(concentrations of drug that inhibited 50% cell growth, IC50). CYS made IC50s of CP in rat and monkey RTEC increase up to more than 5 mM, but BSO made IC50s of CP in rat RTEC lower down with bigger magnitude than that in monkey RTEC; similarly, CYS made IC50s of CP in rat hepatocytes increase up to more than 5 mM, but BSO made IC50s lower down with bigger magnitude than that in rat RTEC. However, neither CYS nor BSO had significant effects on all IC50s of DIC in all examined cells. These results suggested that during CP-induced stress state, rat hepatocytes were more susceptible to changes of GSH level than rat RTEC, and rat RTEC were more dependent on intracellular GSH status than monkey RTEC. DIC-induced cytotoxicity in RTEC and hepatocytes is independent of GSH level.

Animals↗
PubMed2004

Imaging of urethral disease: a pictorial review.

Retrograde urethrography and voiding cystourethrography are the modalities of choice for imaging the urethra. Cross-sectional imaging modalities, including ultrasonography, magnetic resonance (MR) imaging, and computed tomography, are useful for evaluating periurethral structures. Retrograde urethrography is the primary imaging modality for evaluating traumatic injuries and inflammatory and stricture diseases of the male urethra. Sonourethrography plays an important role in the assessment of the thickness and length of bulbar urethral stricture. Although voiding cystourethrography is frequently used to evaluate urethral diverticula in women, MR imaging is highly sensitive in the demonstration of these entities. MR imaging is also accurate in the local staging of urethral tumors.

Adult↗
PubMed2004

CT urography.

With the recent introduction of multi-detector row helical computed tomography (CT), the radiologic evaluation of patients with urologic disease has changed rapidly. Two major approaches to CT urography have been developed. The first approach combines axial CT with timed excretory urography (EU) performed by using conventional radiography, digital radiography, or CT scanned projection radiography (SPR). This approach produces traditional projection urograms, and the timed imaging technique is familiar to radiologists and clinicians. Additional excretory phase CT can be performed when the EU findings are positive or indeterminate. Improved CT SPR processing technology produces radiographlike images, thus eliminating patient transportation between the CT and urography suites or the necessity for a CT suite with a ceiling-mounted x-ray tube and a modified CT tabletop for performance of EU. The second approach to CT urography combines axial CT with thin-section excretory phase CT. The near-isotropic volume data set enables creation of high-resolution two- and three-dimensional reformatted images. However, the increased amount of radiation and the time required for data manipulation are concerns. Further studies evaluating large numbers of patients with various urothelial abnormalities will be necessary to determine the optimal CT urography technique for clinical practice.

Equipment Design↗
PubMed2003

Effects of an angiotensin II receptor antagonist and angiotensin-converting enzyme inhibitors on burst forming units-erythroid in chronic hemodialysis patients.

BACKGROUND: Angiotensin-converting enzyme (ACE) inhibitors have been reported to reduce the response to erythropoietin (EPO) administration in chronic hemodialysis patients, but the mechanism for this effect has not yet been clarified. To clarify the mechanism of ACE inhibitors- and angiotensin II type 1 (AT1) receptor antagonist-induced anemia in hemodialysis patients, we examined the effect of ACE inhibitors and AT1 receptor antagonist on burst-forming units-erythroid (BFU-E) in the peripheral blood of hemodialysis patients and healthy controls in vitro. METHODS: Peripheral blood mononuclear cells (PBMNCs) were isolated by gradient centrifugation from 10 patients on regular hemodialysis and 7 healthy control volunteers. A colony assay of hematopoietic progenitors was performed using the methylcellulose culture system. PBMNCs of 1 or 2 x 10(5) were plated in a medium containing EPO with various concentrations of ACE inhibitors or AT1 receptor antagonist and incubated for 14 days. Colonies of BFU-E were counted under an inverted microscope. RESULTS: The PBMNCs from the chronic hemodialysis patients formed fewer BFU-Es than those from healthy volunteers. AT1 receptor antagonist in both healthy volunteers and hemodialysis patients suppressed the number of BFU-Es. The ACE inhibitors produced a smaller effect than the AT1 receptor antagonist. CONCLUSION: AT1 receptor blockade can directly inhibit erythropoiesis in vitro.

Adult↗
PubMed2003

Design and synthesis of the tumor-activated prodrug of dihydropyrimidine dehydrogenase (DPD) inhibitor, RO0094889 for combination therapy with capecitabine.

A series of tumor-activated prodrugs of the inhibitors of dihydropyrimidine dehydrogenase (DPD), an enzyme catabolizing 5-fluorouracil (5-FU: 4g), has been designed and synthesized. RO0094889 (11c) is a prodrug of 5-vinyluracil (4c), a known DPD inhibitor, and was designed to generate 4c selectively in tumor tissues by sequential conversion of 11c by three enzymes: esterase, cytidine deaminase and thymidine phosphorylase, the latter two of which are known to be highly expressed in various tumor tissues. When capecitabine (1), a tumor-activated prodrug of 5-FU, was co-administered orally with 11c, 5-FU in tumor tissues was significantly increased with only a slight increase of 5-FU in plasma as compared with oral capecitabine alone.

Administration, Oral↗
PubMed2003

Hemorrhagic rectal ulcer caused by a deformity of the coccyx complicated by normal delivery.

A 25-year-old woman delivered her first-born child weighing 3400 g by full-term normal delivery. Bloody stool developed 3 days after delivery. Colonoscopic examination revealed two linear ulcers parallel to the anal column on the posterior side of the rectal ampulla about 5 cm from the anal ring. Coagulated blood was detected at the ulcer bottom, suggesting the site of hemorrhage. Bowel rest in the absence of oral intake resulted in the disappearance of bloody stool. Three days later colonoscopic examination revealed improvement in the ulcer. There was no sign of constipation. A lateral pelvic radiograph showed that the apex of the coccyx was flexed anteriorly. The parturient canal may have physically pressed the rectum against the apex of the coccyx during delivery, causing mucosal injury. Only a few studies have reported the complication of a rectal ulcer due to injury during delivery. Furthermore, none of the previous studies has reported a rectal ulcer caused by deformity of the coccyx.

Coccyx↗
PubMed2003

Evaluation of renal causes of hypertension.

There are many renal causes of hypertension. Although RAS is the most common, other renal lesions can result in hypertension. Any evaluation of the kidney for hypertension should take all of these potential renal etiologies into consideration.

Diagnostic Imaging↗