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Biomedical subjects

I Fujita

Publications and source records attributed to I Fujita.

At least 37 records · Page 2Linked to original sources

Ulinastatin, an elastase inhibitor, inhibits the increased mRNA expression of prostaglandin H2 synthase-type 2 in Kawasaki disease.

Kawasaki disease is an inflammatory disease of unknown cause that causes panvasculitis, including coronary arteritis. Polymorphonucleocytosis in the early stage of the illness suggests the implication of neutrophils in the pathogenesis of the disease. In the acute phase of Kawasaki disease, mRNA expression of prostaglandin H2 synthase (PHS)-2, as determined by reverse transcription-polymerase chain reaction, was markedly enhanced, and thromboxane A2 (TXA2)-synthesizing activity was increased in polymorphonuclear leukocytes (PMNL). This up-regulation of PHS-2 was suppressed by ulinastatin (a neutrophil-elastase inhibitor) treatment. Lipopolysaccharide-induced enhancement of PHS-2 mRNA was also inhibited by therapeutic doses of ulinastatin in vitro by use of PMNL from healthy volunteers. Thus, ulinastatin inhibits arachidonate PHS metabolism by inhibiting new induction of PHS-2 at the mRNA level, which is a novel pharmacologic action of this substance. Ulinastatin treatment is possibly an additional therapeutic approach to Kawasaki disease.

Aspirin↗

Disparity selectivity of neurons in monkey inferior temporal cortex.

The inferior temporal cortex (IT) of the monkey, a final stage in the ventral visual pathway, has been known to process information on two-dimensional (2-D) shape, color, and texture. On the other hand, the dorsal visual pathway leading to the posterior parietal cortex has been known to process information on location in space. Likewise, neurons selective for binocular disparity, which convey information on depth, have been found mainly in areas along the dorsal visual pathway. Here, we report that many neurons in the IT are also selective for binocular disparity. We recorded extracellular activity from IT neurons and found that more than half of the neurons changed their response depending on the disparity added. The change was not attributed to monocular responses or eye movements. Most neurons selective for disparity were "near" or "far" cells; they preferred either crossed or uncrossed disparity, and only a small population was tuned to zero disparity. Disparity-selective neurons were also selective for shape. Most preferred the same type of disparity irrespective of the shape presented. Disparity preference was also invariant for the fronto-parallel translation of the stimuli in most of the neurons. Finally, nearby neurons exhibited similar disparity selectivity, suggesting the existence of a functional module for processing of binocular disparity in the IT. From the above and our recent findings, we suggest that the IT integrates shape and binocular disparity information, and plays an important role in the reconstruction of three-dimensional (3-D) surfaces.

Animals↗

Markers for bone metabolism in a long-lived case of thanatophoric dysplasia.

We report a male patient with type 1 thanatophoric dysplasia, now eight years old, having a mutation in the FGFR3 gene. Radiological examination at birth revealed that the ribs and the bones of the extremities were very short and vertebral bodies were greatly reduced in height with wide intervertebral spaces. The femurs were shaped like French telephone receivers. Because of respiratory insufficiency due to the narrow thorax, the patient has been intubated and supported by continuous mechanical ventilation since the day after birth. Since 5 years of age, despite sufficient caloric intake, his body weight never increased above 4700 g, body height 49.0 cm, head circumference 46.1 cm, and chest circumference 35.8 cm. Acanthosis nigricance and huge bilateral coral-like urolithiases has been present. His mental development was severely retarded but he was able to make emotional expressions. Although developments in motor functions could not be assessed, his neurodevelopmental milestones in social relationships and language perception seemed to be at the level of a 10 to 12 month old. His bone maturation was also severely retarded. All of the assays of his serum and urinary bone formation- or resorption-related substances were within normal limits for age. Therefore, bone formation as well as bone resorption activities seemed normal and not responsible for his growth retardation.

Biomarkers↗

Bioelectrical impedance analysis in the clinical management of a pregnant woman undergoing dialysis.

We report a case of successful pregnancy in a woman who was initially diagnosed with renal failure in mid-pregnancy. She was started on hemodialysis, and her fluid balance was serially monitored with bioelectrical impedance analysis. Her body weight decreased and bioelectrical impedance values increased, along with resolution of pulmonary edema in the process of the removal of excessive fluid retention with hemodialysis. The bioelectrical impedance values decreased immediately after the usual dose of oral ritodrine was administered, partly because producing sodium and water retention by ritodrine were enhanced in the setting of fluid imbalances. This decrease preceded the onset of pulmonary edema, while no changes were noted in maternal body weight before hemodialysis. These results suggest that the serial measurement of bioelectrical impedance values enables more reliable and earlier detection of abnormal water retention in pregnant women undergoing dialysis than the effect of body weight changes.

Adult↗

Metallothionein acts as a cytoprotectant against doxorubicin toxicity.

The protective role of metallothionein (MT) against the myocardiotoxicity and hepatotoxicity of doxorubicin (Dox) was investigated in mice. Dox-induced elevations of plasma creatine kinase activity, a measure of myocardiac damage, and plasma glutamate pyruvate transaminase activity, reflecting hepatic damage, were prevented by pretreatment with an MT inducer. Pretreatment with zinc induced MT in the liver and heart, thereby reducing Dox toxicity in these two organs. Pretratment with n-hexane also induced MT and reduced Dox toxicity, but only in the liver. In primary hepatocyte cultures, the leakage of lactate dehydrogenase induced by Dox was prevented by zinc pretreatment. These results suggest that MT induction prevents Dox toxicity in vivo and in vitro. Furthermore, we determined that MT-null mice were more sensitive to the myocardiotoxic and hepatotoxic effects of Dox. These findings indicate that both basal and induced MT protect against Dox toxicity.

Alanine Transaminase↗

[Adenocarcinoma of the ileal segment with transitional cell carcinoma of the bladder following ileocytoplasty: a case report].

A 67 year-old woman visited our hospital complaining of pollakisuria. She had undergone left nephrectomy and augmentation ileocystoplasty for tuberculous bladder atrophy 40 years previously. She underwent a total cystectomy and tubeless ureterocutaneostomy with a preoperative diagnosis of muscle-invading transitional cell carcinoma of the bladder. The pathological diagnosis was adenocarcinoma of the ileal segment and transitional cell carcinoma of the original bladder. This is the first case report of adenocarcinoma of the ileal segment and transitional cell carcinoma of the original bladder among 22 patients suffering from bladder cancer after ileocystoplasty.

Adenocarcinoma↗

[A case of synchronous ipsilateral renal cell carcinoma and ureteral transitional cell carcinoma].

A 62-year-old man was admitted to our hospital with the chief complaint of right flank pain. Abdominal computed tomographic scan revealed a right hydronephrosis and intrapelvic tumor. Ultrasound revealed a renal mass lesion. Ultrasound guided renal biopsy and laparotomy of intrapelvic tumor was performed. The histopathological diagnosis was renal cell carcinoma and ureteral transitional cell carcinoma.

Biopsy↗

"Malignant struma ovarii" with peritoneal metastasis: report of two cases.

Malignant struma ovarii with metastasis in an extremely rare form of ovarian carcinoma. We describe two cases of malignant struma ovarii that demonstrated widespread peritoneal metastases. In the second case described here, furthermore, the tumor recurred II years later in the contralateral ovary and omentum, while the primary tumor previously was pure struma ovarii with no evidence of metastasis. Although thyroid tumors themselves are characterized by a long latent interval, patients with benign thyroid tissue arising in nonthyroidal organs with or even without dissemination should be managed with caution and need appropriate long-term follow-up after the initial surgery.

Adult↗

Liposarcoma of the uterine cervix: case report.

A case of primary liposarcoma of the cervix is described in a 49-year-old woman with a fungating cervical mass which was diagnosed as liposarcoma on the basis of cytologic features and the intracellular lipids. Most of the adipocytes and vacuolated lipoblasts were positive for S- 100 protein. The mass was well circumscribed and limited to the superficial cervical stroma. A total abdominal hysterectomy and bilateral salpingo-oophorectomy with pelvic lymphadenectomy was performed. There was no clinical evidence of metastasis two years after the operation.

Female↗

Distinct mechanisms of transport of ascorbic acid and dehydroascorbic acid in intestinal epithelial cells (IEC-6).

Ascorbic acid (AsA) is an essential nutrient for humans as they lack its biosynthesizing key enzyme. Its absorption mechanism in small intestinal epithelial cells still remains to be resolved. In this study, the transport mechanisms functioning on the uptake of AsA and its oxidized form, dehydroascorbic acid (DHA), were investigated using rat small intestinal epithelial cell line IEC-6. Both AsA and DHA were accumulated in the cells in time- and concentration-dependent manners, but their absorption kinetics were apparently different. The saturability of AsA uptake was shown at a considerably lower concentration in IEC-6 cells as well as other mammalian cells, indicating that this absorption was mediated by a specific transporting carrier. The absorption efficiency of AsA was about 1/5-1/10 that of DHA at the same concentration range and, moreover, the uptake of DHA was almost comparable to that of 2-deoxy-D-glucose, an alternative of glucose. The uptake of AsA was diminished by the removal of sodium ion, but not by the addition of glucose, whereas that of DHA was sodium ion-independent and effectively inhibited by glucose. In addition, phlorizin and cytochalasin B, which are blockers of glucose transporters, interfered the uptake of DHA more efficiently than that of AsA. These results indicate that there are at least two distinct transport systems of vitamin C in rat small intestinal epithelial cells; AsA is transported by a specific transporter and DHA is mainly transported by glucose transporter(s).

Animals↗

Behavioral evidence for visual perception of 3-dimensional surface structures in monkeys.

Human subjects perceive two crossing bars, one in front of the other, when shown a cross with disparity added to its horizontal limbs, and they also perceive neon-color spreading when shown a stereoscopic Redies-Spillmann figure. It has thus been hypothesized that the human visual system follows the principle of generic image sampling in reconstructing 3-dimensional (3-D) surface structures. Here we examine whether monkeys also perceive these surface structures. The results indicate that monkeys, like humans, perceive two crossing bars and neon-color spreading and suggest that the principle of generic image sampling may also be applied to visual perception in monkeys.

Animals↗

Distribution, morphology, and gamma-aminobutyric acid immunoreactivity of horizontally projecting neurons in the macaque inferior temporal cortex.

In area TE of the macaque inferior temporal cortex, horizontal axons running parallel to the pial surface mediate interactions between laterally displaced sites across the cortex. We examined the spatial distribution and the types of cells that give rise to these horizontal axons, which are important factors in determining the nature of the lateral interactions in TE. Intracortical injections of retrograde tracers labeled columnar clusters of cells and cells diffusely scattered within TE. The clusters were 0.35 +/- 0.11 mm (mean +/- SD) in diameter and were laterally distributed up to 6 mm from the injection site. Labeled cells were found in layers 2 to 6, with only a few labeled cells seen in layer 4. The clustering of labeled cells in layers 5 and 6 was looser than that in layers 2 and 3. Intracellular staining of the retrogradely labeled cells revealed that the majority of them were typical or modified pyramidal cells, both within and between the clusters. Only a few nonpyramidal interneurons were also stained at the fringe of the tracer injection site. Consistent with these results, only a small proportion of the retrogradely labeled cells exhibited gamma-aminobutyric acid (GABA)-like immunoreactivity, mostly found within 1 mm from the injection site. The results indicate that direct horizontal interactions in TE are predominantly mediated by pyramidal or modified pyramidal cells in layers 2, 3, 5, and 6 and are primarily excitatory in nature. The contribution of GABAergic interneurons to direct horizontal interactions is restricted to only short-distance projections.

Animals↗

Tissue accumulation of cadmium following oral administration to metallothionein-null mice.

To verify the roles of intestinal metallothionein (MT) as a barrier against ingested cadmium (Cd) and as a transporter of mucosal Cd to the kidneys, the distribution of orally administered Cd was compared between normal and MT-I and -II knock-out (MT-null) mice. Following single administration of a low dose of Cd (0.1 mg/kg), hepatic Cd levels and the sum of total Cd in the liver and kidney (K + L) were significantly less in the controls than in MT-null mice. The ratio of Cd in the kidney to the liver (K/L) was significantly lower in the MT-null mice. On the other hand, at a high Cd dose (2.0 mg/kg), K + L and K/L were not significantly different between the two groups. However, following oral pretreatment with zinc (Zn) to the high dose control mice, K + L significantly decreased and K/L significantly increased. No such effects of Zn pretreatment were observed in MT-null mice. Similar differences in K + L and K/L were also observed between the control and MT-null mice groups following the Zn pretreatment. Repeated administration of Cd for 4 weeks resulted in significantly larger K/L distribution in control mice over null mice. These results suggest that MT in the intestinal mucosa functions both as a protective barrier against Cd absorption and as an extracellular transporter of Cd to the kidney.

Administration, Oral↗

Identification of amine acceptor protein substrates of transglutaminase in liver extracts: use of 5-(biotinamido) pentylamine as a probe.

Transglutaminase is a calcium-dependent enzyme which catalyzes amine incorporation and cross-linking of proteins. To isolate the amine acceptor protein substrates of transglutaminase in mammalian livers, a biotin-labeled primary amine substrate of transglutaminase, 5-(biotinamido) pentylamine, was used for biotin labeling of proteins in the liver extracts by endogenous transglutaminase activity. The biotin-labeled proteins were isolated and recovered by biotin-avidin-affinity chromatography. The obtained proteins were separated by SDS-PAGE. Proteins with molecular masses of 15, 24, 35, 40, 44, 93, and 134 kDa were the main components of labeled proteins in mouse liver extract. In rat and guinea pig liver extracts, 32-, 38-, 40-, 44-, and 134-kDa proteins and28-, 40-, 44-, 55-, 60-, 91-, and 134-kDa proteins were the main components of labeled proteins, respectively.Using amino-terminal amino acid sequence analyses and sequence homology searches, the 38-kDa protein from rat liver was identified as a subunit of glyceraldehyde-3-phosphate dehydrogenase (EC 1.2.1.12), and the 28-kDa protein from guinea pig liver was identified as a subunit of glutathione S-transferase (class theta) (EC 2.5.1.18). Both the glyceraldehyde-3-phosphate dehydrogenase from rabbit muscle and glutathione S-transferase (class pi) from human placenta also could be amine acceptors in the amine incorporation catalyzed by guinea pig liver transglutaminase. These results suggest that these enzymes can be modified posttranslationally by cellular transglutaminase.

Amines↗

The interaction of preserved pragmatics and impaired syntax in Japanese and English aphasic speech.

Elicited narrative studies have shown that the underlying pragmatic factor of empathy is relatively preserved in aphasic speakers of Japanese and English (7 Japanese and 14 English-speaking aphasics of varied diagnostic types). Occasional "reversal errors" can be explained in terms of a conflict between the normal encoding of the empathic characteristics of an event and the syntactic limitations imposed by impaired production processes. To account for these findings, we propose a production model following Levelt (1989) for making pragmatic choices among syntactic forms. We also suggest that preferential access to "canonical form" might be a matter of surface morphosyntax, rather than involving semantics or more abstracts levels of syntax.

Adolescent↗

Exercise-induced acute renal failure in a girl with renal hypouricemia.

A 10-year-old Japanese girl developed acute renal failure following a 100-meter dash during physical training at school. After the run, she experienced intense pain in the loins with nausea and vomiting lasting more than 12 h. On the following morning, she was found to have mild proteinuria and acute renal failure (ARF). Serum creatinine and blood urea nitrogen were elevated, but the serum uric acid level was normal (3.1 mg/dL). With recovery of renal function over the ensuing days, hypouricemia (0.6 mg/dL) became evident in the patient. Although the pathophysiological association between renal hypouricemia and ARF is not known, oxygen free radicals have been implicated in the pathogenesis for ischemic-reperfusion ARF. Superoxide production by neutrophils stimulated by N-formyl methionine leucyl-phenylalanine was normal in the patient both before and following exercise. Pyrazinamide and probenecid tests were undertaken on both the patient and her parents, who had borderline hypouricemia, to determine their renal tubular handling of uric acid. Results showed that the patient and her mother had a subtotal reabsorption defect, while the father had defective postsecretory uric acid reabsorption.

Acute Kidney Injury↗

[Successful treatment of hepatic metastasis of gastric cancer with 5'-DFUR and Lentinan].

Satisfactory therapeutic effects are rarely obtained with oral chemotherapy for gastric cancer. We have experienced successful treatment for synchronous hepatic metastasis of gastric cancer with 5'-DFUR and Lentinan. The patient was a 78-year-old female, diagnosed as having gastric cancer with multiple hepatic metastases, who underwent gastrectomy. Immunohistochemistry of the resected specimens with anti-thymidine phosphorylase (dThdPase) antibody yielded positive results for dThdPase in the primary tumor as well as the hepatic metastases. Two months after surgery, administration of 400 mg of 5'-DFUR per day and 2 mg i.v. of Lentinan every other week was started. Four months after discharge, carcinoembryonic antigen (CEA) in plasma showed an abrupt logarithmic decline. Furthermore, a 99% reduction in hepatic metastases was demonstrated by abdominal CT. At present, 22 months after surgery, the patient is managed on an outpatient basis with no complaints of any side effects. Immunochemotherapy using 5'-DFUR and Lentinan may be effective against gastric malignancies expressing dThdPase activity.

Adenocarcinoma↗