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Biomedical subjects

Y Fujii

Publications and source records attributed to Y Fujii.

At least 595 records · Page 33Linked to original sources

Analysis of the circumstances of death of 56 children suffering from cancer: proposal for the development of terminal medicine in Japan.

In Japan terminal medicine for children dying from cancer has not yet been developed nor has a support system for home terminal care and bereaved families been established. We have analyzed our own experiences in these areas and researched the possibilities of establishing support systems. In the 16 years from 1978 to 1993, 56 children with cancer have been treated and have died at Hamamatsu University Hospital. We analyzed the circumstances of their deaths. We interviewed 25 sets of parents about their acceptance of their child's death. Three children (5%) died unexpectedly during treatment, 27 children (48%) died from the side-effects of intensive treatment, and 26 children (47%) died during terminal care. More children with leukemia and lymphoma died from side-effects than children with solid tumors (P < 0.05). Six out of the 25 families had not yet accepted the loss of their child due to regrets associated with the missed opportunity for terminal care. From our experiences with the five children who received terminal care at home, we recognize the need for a support system run by the hospital and conclude the time is ripe for initiating home-based terminal care in Japan.

Child↗

Magnetic resonance imaging for the diagnosis of prostate cancer metastatic to bone.

OBJECTIVE: To examine the role of magnetic resonance imaging (MRI) in the evaluation of osseous metastasis in patients with prostate cancer. PATIENTS AND METHODS: A series of 36 patients with known prostate cancer, who were undergoing MRI and an isotope bone scan, were studied. RESULTS: Of 19 positive bone scans, MRI was read as negative for metastasis in one. Of eight equivocal scans, two MR images were interpreted as positive and six as negative. Of nine negative scans MRI was positive in one. Further MRI demonstrated additional metastatic lesions that were not shown by bone scintigraphy in six patients. MRI clearly indicated the areas of spinal cord compression in five patients with spinal metastases and associated myelopathy. CONCLUSION: MRI is helpful in the diagnosis of metastatic prostate cancer, especially when other radiographic examinations are inconclusive or spinal cord compression is suspected.

Bone Neoplasms↗

Disulfide bond formation and secretion of Escherichia coli heat-stable enterotoxin II.

The Escherichia coli heat-stable enterotoxin II (STII) is a typical extracellular toxin consisting of 48 amino acid residues, of which 4 are cysteine. There are two disulfide bonds, one between Cys-10 and Cys-48 and one between Cys-21 and Cys-36. We examined the involvement of DsbA in the formation of the disulfide bonds of STII and the role of each in the secretion of STII. A dsbA mutant was transformed with a plasmid harboring the STII gene, and STII was not detected either in the cells or in the culture supernatant. Reducing the level of STII brought about the dsbA mutation restored by introducing the wild-type dsbA gene into the mutant strain. These results showed that DsbA is involved in forming the disulfide bonds of STII and that STII without these disulfide bonds is degraded during secretion. We substituted these four cysteine residues in vivo by oligonucleotide-directed site-specific mutagenesis. The amino acid sequence of the purified STII (C48S) and pulse-chase studies revealed that two intermolecular disulfide bonds must be formed to be efficiently secreted and that cleavage between amino acid residues 14 and 15 is probably the first step in the proteolytic degradation of STII.

Bacterial Toxins↗

Metabolic alterations in the neonate and infant brain during development: evaluation with proton MR spectroscopy.

PURPOSE: To evaluate the usefulness of hydrogen-1 magnetic resonance (MR) spectroscopy in the evaluation of the developing brain. MATERIALS AND METHODS: Localized MR spectra were obtained with an echo time of 272 msec from the brain of 78 neonates and infants aged 1 week to 100 months. All patients were retrospectively classified into three groups on the basis of neurologic development: abnormal (group 2, n = 21), normal despite minor neurologic signs (group 1, n = 23), and normal (group 0, n = 34). RESULTS: Seventeen patients in group 2 and eight patients in group 1 revealed abnormally low N-acetylaspartate (NAA)/choline or NAA/creatine ratios compared with those obtained in group 0. MR spectroscopy was slightly more useful in the differentiation of patients in groups 2 and 1 (chi 2 test, P < .005) than MR imaging (P < .01). CONCLUSION: H-1 MR spectroscopy provides prognostic information about the brain in healthy and neurologically damaged infants and augments the value of MR imaging.

Aspartic Acid↗

Bone mineral status in preterm-born children: assessment by dual-energy X-ray absorptiometry.

To elucidate the long-term consequences of osteopenia of prematurity, lumbar spinal bone mass was measured in 21 preterm-born children aged 3-4 years by dual-energy X-ray absorptiometry. Their mineral intake remained low during early life, and all 11 infants previously studied were osteopenic at term postconception. At the age of 3-4 years, however, all 21 children were found to have normal bone mineral content and density with slightly elevated serum osteocalcin levels. Our results show that in preterm-born children spontaneous resolution of lumbar spinal osteopenia occurs during early childhood.

Absorptiometry, Photon↗

Ultrastructural study of basal lamina of retinal pigment epithelium.

The ultrastructure of basal lamina (BL) of retinal pigment epithelium (RPE) in guinea pigs was studied by the quick-freezing, deep-etching (QF-DE) method. The retinal tissue was quickly frozen, fractured and deeply etched. A replica was prepared by shadowing with platinum and carbon. Electron micrographs of the BL of RPE provide a three-dimensional (3-D) ultrastructure. The lamina lucida was filled with traversing filamentous structures, which connected the basal infolding of RPE with the lamina densa. The lamina densa consisted of a 3-D meshwork structure. It is suggested that the traversing filamentous structures in the lamina lucida might play a role in anchoring the basal infolding of RPE and in maintaining the normal architecture.

Animals↗

Benign renal tumors detected among healthy adults by abdominal ultrasonography.

Renal ultrasonography was performed on 17,941 healthy adults without any signs suggestive of urinary tract malignancies. Diffusely hyperechoic renal masses indicative of angiomyolipoma were found in 41 (0.23%) of them and those with echogenic image suggestive of renal cell carcinoma in 45 (0.25%). Final diagnosis of the former group included 24 angiomyolipoma, 1 renal cell carcinoma, 9 calculus and 7 normal variants. The latter group included 19 renal cell carcinomas, 1 leiomyoma, 1 cavernous hemangioma and 24 normal variants or cysts. In total, 24 (0.13%) angiomyolipomas, 20 (0.11%) renal cell carcinomas, 1 leiomyoma, and 1 cavernous hemangioma were discovered. The results indicate that asymptomatic benign renal tumors mainly consisting of angiomyolipoma are not uncommon.

Adult↗

Molecular diversity and functional characterization of voltage-dependent calcium channels (CACN4) expressed in pancreatic beta-cells.

Dihydropyridine-sensitive voltage-dependent calcium channels (VDCC) play a crucial role in insulin secretion. We recently have cloned a human alpha 1-subunit of the VDCC expressed in pancreatic beta-cells, designated CACN4. In this study we have isolated complementary DNAs encoding two forms of rat CACN4 (rCACN4A and rCACN4B) from a rat insulinoma RINm5F complementary DNA library. Rat CACN4A is a protein of 2203 amino acids and is the rat homolog of human CACN4, whereas rCACN4B lacks 535 amino acids in the carboxyl-terminal region, probably due to alternative splicing. We have found two additional variations, one in the intracellular loop between repeats I and II and the other in the extracellular region between the third and fourth segments of repeat IV. Reverse transcriptase-polymerase chain reaction analysis of rat pancreatic islet messenger RNA reveals that these variants are present in pancreatic islets. In addition, whole-cell voltage-clamp recordings of Chinese hamster ovary cells stably expressing the alpha 1-subunit (rCACN4A or rCACN4B) with or without the calcium channel beta 2-subunit show that coexpression of rCACN4A with the beta 2-subunit or rCACN4B with the beta 2-subunit elicits L-type VDCC currents, whereas expression of the alpha 1-subunit alone does not, indicating that CACN4 can associate functionally with the beta 2-subunit and that the beta-subunit is essential for functional expression of CACN4. These results suggest that there are various subtypes of CACN4 expressed in pancreatic beta-cells, and that both rCACN4A and rCACN4B can function as VDCC. Furthermore, the present study suggests that the expression of the beta-subunit as well as the alpha 1-subunit may participate in the regulation of insulin secretion.

Amino Acid Sequence↗

Hemostasis in spontaneous subarachnoid hemorrhage.

To comprehensively examine changes in the hemostatic systems early after spontaneous subarachnoid hemorrhage (SAH) and to assess the relationships between those changes and neurological findings, computed tomographic findings, and clinical outcomes, we reviewed 167 patients who were admitted within 24 hours of the onset of SAH. Blood was taken from all of the patients at admission for detailed examinations of the hemostatic systems. The following results were obtained: 1) the levels of the thrombin-antithrombin complex (elevation indicating the activation fo the blood coagulation system), plasmin-antiplasmin complex, and D-dimer (elevation indicating the activation of the fibrinolytic system) significantly increased with the neurological severity, amount of subarachnoid clot, and severity of clinical outcome; 2) the levels of the thrombin-antithrombin complexes and plasmin-antiplasmin complexes were significantly higher in patients with intracerebral or intraventricular hematomas than in patients without those hematomas; 3) in each of almost all the neurological and computed tomographic grades, the levels of the thrombin-antithrombin complexes were significantly higher in the patients with poor outcomes than in those with good outcomes; 4) the poor outcome rate significantly increased with neurological severity and the amount of subarachnoid clot. These data suggest that the activation of the blood coagulation system as well as of the fibrinolytic system occurred early in the course of SAH and that these systems were activated to a greater extent with the severity of neurological grades, computed tomographic findings, and clinical outcome.(ABSTRACT TRUNCATED AT 250 WORDS)

Aneurysm, Ruptured↗

Effects of diaphragmatic plication on respiratory mechanics in dogs with unilateral and bilateral phrenic nerve paralyses.

To examine the effects of diaphragmatic plication on respiratory mechanics during spontaneous breathing, we grouped 28 dogs into left phrenicotomy and plication (group L, n = 11), bilateral phrenicotomy and plication (group B, n = 9), and sham operations (group C, n = 8). In groups L and B, phrenicotomy caused significant (p < 0.05) decreases in tidal volume (VT), transdiaphragmatic pressure (delta Pdi), the ratio of gastric to esophageal pressure (delta Pga/delta Pes) and dynamic lung compliance (Cdyn), and significant (p < 0.05) increases in esophageal pressure (delta Pes), and the work of breathing (WOB) per liter of ventilation. In group L, plication resulted in significant (p < 0.05) increases in VT, delta Pdi, delta Pga/delta Pes, and Cdyn, and a significant reduction of WOB compared with phrenicotomy condition, indicating an improvement in the respiratory mechanics. However, in group B, no significant changes were observed after plication except for increased VT. In eight left-phrenicotomized open-chest dogs, transdiaphragmatic pressure (Pdi) and fractional shortening (FS) of right hemidiaphragm by right phrenic nerve stimulation increased significantly (p < 0.05) after plication, compared with the phrenicotomy condition, suggesting more effective kinetics of the right hemidiaphragm after plication of the left hemidiaphragm. Our results showed that diaphragmatic plication for unilateral paralysis is more effective than for bilateral paralysis, indicating that an improvement in kinetics of the intact hemidiaphragm plays an important role in functional recovery.

Animals↗

[A case of angiosarcoma with renal failure caused by recombinant interleukin-2 (rIL-2) and non-steroid anti-inflammatory drug (NSAID)].

A 77-year-old man was diagnosed to have diabetes. He was hospitalized for appetite loss, weight loss (6 kg/3 months) and right femoral pain. An abnormal shadow was noted on chest X-P. On admission, he was alert and there were no abnormal physical findings except limitation in the range of motion in the right lower extremity. His femoral pain was treated by a non-steroid anti-inflammatory drug (NSAID). Right femoral bone biopsy revealed angiosarcoma and staining for factor VIII, with negative staining for epithelial membrane antigen on enzyme assay. Therefore, he received systemic administration of recombinant interleukin-2 (rIL-2). rIL-2 was administered intravenously twice daily at a dose of 40 x 10(4) JRU. The total dosage of rIL-2 amounted to 1200 x 10(4) JRU, but renal failure deteriorated and he died on the 50th hospital day of his second admission. Combination of rIL-2 and NSAID may cause progression of nephropathy.

Aged↗

[Magnetic resonance imaging for the evaluation of prostate cancer metastatic to bone].

The response of bone metastatic lesions to endocrine therapy was assessed by repeated magnetic resonance imaging (MRI) and an isotope bone scan after an average period of 7.0 months (2-10 months) in 12 patients with prostate cancer. MRI used both T1-weighted spin echo technique and short TI IR (STIR) sequence. Of 7 patients with hormone-dependent cancer, the bone metastatic lesions resolved or became vague in all patients on STIR image, while in only 4 and 3 on T1-weighted image and bone scan, respectively. Of 5 patients with hormone-refractory cancer, the lesions progressed on both MRI and bone scan in all patients except one who had initially had diffusely metastatic lesions of systemic bone. The results indicate that STIR image of MRI is helpful for the therapeutic evaluation of bone lesions.

Adenocarcinoma↗

Further metabolism of FK506 (tacrolimus). Identification and biological activities of the metabolites oxidized at multiple sites of FK506.

To characterize the metabolic pathway of FK506 (tacrolimus), FK506 or its 31-O-desmethyl metabolite was incubated with liver microsomes prepared from dexamethasone-treated rats in the presence of a NADPH-generating system under aerobic conditions. Besides the four oxidized metabolites already reported, four new metabolites were isolated and identified by HPLC, mass spectrometry, and NMR spectroscopy, and their biological activities were examined. The di-demethylated metabolites at the 15- and 31-, 13- and 31-, and 13- and 15-methoxy groups of FK506, were designated respectively as M-V, M-VI, and M-VII. The fourth, M-VIII, was the metabolite produced after O-demethylation at the 31-methoxy group and formation of a fused 10-membered ring structure through the 19- to 22-carbon of the macrolide ring after oxidation of the 19-methyl group, and of the 36- and 37-vinyl group of FK506. The immunosuppressive activity of the isolated metabolites was estimated in a mouse mixed lymphocyte reaction system and the IC50 values for M-V, M-VI, M-VII, M-VIII, and FK506 were > 1000, 8.78, > 1000, 15.27, and 0.11 ng/ml, respectively. Reactivity of the metabolites with mouse anti-FK506 monoclonal antibody was studied and immunocrossreactivity of M-V was 92.3% of FK506, but no reactivity was observed for M-VI, M-VII, and M-VIII. FK506 thus was metabolized at multiple sites by rat hepatic microsomes and the metabolites formed (M-V) - (M-VIII) exhibited weak or negligible immunosuppressive activity.

Animals↗

Effect of calcium supplementation on bone density and parathyroid function in elderly subjects.

The effect of calcium supplementation on secondary hyperparathyroidism of old age depends on the intestinal absorption of the calcium preparation used. In order to test the bioavailability and clinical usefulness of a new calcium preparation, heated oyster shell-seaweed calcium (HOSS Ca), a randomized, prospective, double-blind comparison of HOSS Ca, calcium carbonate and placebo was carried out in 58 hospitalized women with a mean age of 82. Group A received 900 mg Ca/day Ca as HOSS Ca, group B 900 mg Ca/day as CaCO3 and group C placebo in addition to the basic hospital diet containing approximately 600 mg Ca/day. After 18 months, lumbar spine bone mineral density (BMD) measured by DPX was 106.1 +/- 3.5% (mean +/- SEM) of the pretrial basal value in group A, 99.8 +/- 3.8% in group B and 90.9 +/- 3.4% in group C (A bu not B significantly higher than C). Midradial BMD measured by DPX was 99.3 +/- 1.3% in A, 94.8 +/- 4.0% in B and 85.5 +/- 6.2% in C. The ratio of whole body calcium content between the 12th and 18th month was 96.5 +/- 1.7% in A, 90.1 +/- 2.7% in B and 89.8 +/- 1.3% in C (A but not B significantly smaller than C). Final/baseline ratio of urinary Ca/creatinine was 91.7 +/- 11.1 in A, 111.4 +/- 18.9 in B and 125.2 +/- 12.6 in C.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

[Analysis of malignant potential on colorectal carcinoma utilizing expression of epidermal growth factor and DNA ploidy patterns].

Human epidermal growth factor (EGF) and DNA ploidy patterns were investigated in order to elucidate malignant potential of 216 surgically resected colorectal carcinomas. EGF positive was detected in 140 out of 216 (64.8%) cases and DNA aneuploidy was found in 137 out of 216 (63.4%). No significant correlations were recognized between EGF expressions and DNA ploidy patterns. We subclassified the cases into four groups according to their histological EGF expressions and DNA ploidy patterns. In these groups, the relationship among EGF expressions, DNA ploidy patterns and clinicopathological findings was studied. Subgroups had a significant relation to depth of invasion, lymph node metastasis, lymphatic invasion and clinical stage. In patients with curative operation, the prognosis was significantly lower in EGF-positive-DNA aneuploidy group than in EGF-negative-DNA diploidy group. In DNA diploidy, the prognosis of EGF-positive group was poorer than in the EGF-negative group. In conclusion, the EGF expression as well as DNA ploidy patterns may be useful to assess malignant potential in colorectal carcinoma.

Colorectal Neoplasms↗

[The role of thoracotomy for malignant mediastinal tumors (MMT)-- survey of consecutive 223 patients].

To elucidate the role of surgery for MMT, 214 patients during past 34 years were historically divided into the early (1960-1971, n = 80), intermediate (1972-1981, n = 79) and late series (1982-1993, n = 64). The thoracotomy rate for MMT, the rate of thoracotomy after preoperative diagnosis was done, and the number of postoperative survivors were significantly higher in the late series, compared with the early series. The intermediate series located between the early and late series. Nine patients in the late series undergoing chemo-radiation therapies obtained a good result after complete resection of the residual tissue. We conclude that surgical treatment of MMT should be based on accurate preoperative diagnosis and a distinct role for multidisciplinary treatment, especially regarding malignant thymoma, malignant lymphoma and malignant germ cell tumor.

Adolescent↗