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Biomedical subjects

H Segawa

Publications and source records attributed to H Segawa.

At least 19 recordsLinked to original sources

Long-term results of non-operative treatment of anterior cruciate ligament injury.

We retrospectively reviewed the record of 89 patients with complete anterior cruciate ligament injury, documented by arthroscopic examination to investigate the long-term results in relation to the generation of osteoarthritis. The mean age of the patients was 34.9 years at follow-up and the mean duration of follow-up was 12.0 years. The mean Lysholm score was 89 points at follow-up. The mean Tegner activity score was 5.7 points before injury and 4.5 points at follow-up. Plain radiographs revealed 63% of osteoarthritis and 37% of which had joint space narrowing. The age of the patients, the level of sports activity, the history of meniscectomy, obesity and the osteoarthritis of the contralateral knee were found to be significant risk factors in osteoarthritis after anterior cruciate ligament injury. The most influential factor for osteoarthritis was considered meniscectomy, in combination with the risk factors of primary osteoarthritis. It should also be noted that modification of sports activity level was the most important factor for avoiding the combined injury of meniscus and osteoarthritis.

Adult↗

Transport properties of a system y+L neutral and basic amino acid transporter. Insights into the mechanisms of substrate recognition.

The properties of system y(+)L-mediated transport were investigated on rat system y(+)L transporter, ry(+)LAT1, coexpressed with the heavy chain of cell surface antigen 4F2 in Xenopus oocytes. ry(+)LAT1-mediated transport of basic amino acids was Na(+)-independent, whereas that of neutral amino acids, although not completely, was dependent on Na(+), as is typical of system y(+)L-mediated transport. In the absence of Na(+), lowering of pH increased leucine transport, without affecting lysine transport. Therefore, it is proposed that H(+), besides Na(+) and Li(+), is capable of supporting neutral amino acid transport. Na(+) and H(+) augmented leucine transport by decreasing the apparent K(m) values, without affecting the V(max) values. We demonstrate that although ry(+)LAT1-mediated transport of [(14)C]l-leucine was accompanied by the cotransport of (22)Na(+), that of [(14)C]l-lysine was not. The Na(+) to leucine coupling ratio was determined to be 1:1 in the presence of high concentrations of Na(+). ry(+)LAT1-mediated leucine transport, but not lysine transport, induced intracellular acidification in Chinese hamster ovary cells coexpressing ry(+)LAT1 and 4F2 heavy chain in the absence of Na(+), but not in the presence of physiological concentrations of Na(+), indicating that cotransport of H(+) with leucine occurred in the absence of Na(+). Therefore, for the substrate recognition by ry(+)LAT1, the positive charge on basic amino acid side chains or that conferred by inorganic monovalent cations such as Na(+) and H(+), which are cotransported with neutral amino acids, is presumed to be required. We further demonstrate that ry(+)LAT1, due to its peculiar cation dependence, mediates a heteroexchange, wherein the influx of substrate amino acids is accompanied by the efflux of basic amino acids.

Amino Acid Transport Systems, Basic↗

Identification and characterization of a Na(+)-independent neutral amino acid transporter that associates with the 4F2 heavy chain and exhibits substrate selectivity for small neutral D- and L-amino acids.

A cDNA was isolated from the mouse brain that encodes a novel Na(+)-independent neutral amino acid transporter. The encoded protein, designated as Asc-1 (asc-type amino acid transporter 1), was found to be structurally related to recently identified mammalian amino acid transporters for the transport systems L, y(+)L, x(C)(-), and b(0,+), which are linked, via a disulfide bond, to the type II membrane glycoproteins, 4F2 heavy chain (4F2hc), or rBAT (related to b(0,+) amino acid transporter). Asc-1 required 4F2hc for its functional expression. In Western blot analysis in the nonreducing condition, a 118-kDa band, which seems to correspond to the heterodimeric complex of Asc-1 and 4F2hc, was detected in the mouse brain. The band shifted to 33 kDa in the reducing condition, confirming that Asc-1 and 4F2hc are linked via a disulfide bond. Asc-1-mediated transport was not dependent on the presence of Na(+) or Cl(-). Although Asc-1 showed a high sequence homology (66% identity at the amino acid level) to the Na(+)-independent broad scope neutral amino acid transporter LAT2 (Segawa, H., Fukasawa, Y., Miyamoto, K., Takeda, E., Endou, H., and Kanai, Y. (1999) J. Biol. Chem. 274, 19745-19751), Asc-1 also exhibited distinctive substrate selectivity and transport properties. Asc-1 preferred small neutral amino acids such as Gly, L-Ala, L-Ser, L-Thr, and L-Cys, and alpha-aminoisobutyric acid as substrates. Asc-1 also transported D-isomers of the small neutral amino acids, in particular D-Ser, a putative endogenous modulator of N-methyl-D-aspartate-type glutamate receptors, with high affinity. Asc-1 operated preferentially, although not exclusively, in an exchange mode. Asc-1 mRNA was detected in the brain, lung, small intestine, and placenta. The functional properties of Asc-1 seem to be consistent with those of a transporter subserving the Na(+)-independent small neutral amino acid transport system asc.

Amino Acid Sequence↗

Boomerang deformity of cervical spinal cord migrating between split laminae after laminoplasty.

Patients with cervical compression myelopathy were studied to elucidate the mechanism underlying boomerang deformity, which results from the migration of the cervical spinal cord between split laminae after laminoplasty with median splitting of the spinous processes (boomerang sign). Thirty-nine cases, comprising 25 patients with cervical spondylotic myelopathy, 8 patients with ossification of the posterior longitudinal ligament, and 6 patients with cervical disc herniation with developmental canal stenosis, were examined. The clinical and radiological findings were retrospectively compared between patients with (B group, 8 cases) and without (C group, 31 cases) boomerang sign. Moderate increase of the grade of this deformity resulted in no clinical recovery, although there was no difference in clinical recovery between the two groups. Most boomerang signs developed at the C4/5 and/or C5/6 level, where maximal posterior movement of the spinal cord was achieved. Widths between lateral hinges and between split laminae in the B group were smaller than in the C group. Flatness of the spinal cord in the B group was more severe than in the C group. In conclusion, the boomerang sign was caused by posterior movement of the spinal cord, narrower enlargement of the spinal canal and flatness of the spinal cord.

Adult↗

Radiosurgery of meningeal melanocytoma.

The authors present a case of meningeal melanocytoma arising from Meckel's cave. A coal-black, vascular tumor was partially removed by surgery. Histopathologically, the tumor lacked anaplastic features. Immunohistochemical studies confirmed that the tumor was of neuroectodermal origin and had low proliferating activity. The patient underwent gamma knife radiosurgery for the residual tumor, in which 25 Gy of radiation was delivered to the tumor margin. Three years after irradiation, the tumor showed marked shrinkage without complication.

Adult↗

Identification and functional analysis of three isoforms for the Na+-dependent phosphate co-transporter (NaPi-2) in rat kidney.

We have isolated three unique NaPi-2-related protein cDNAs (NaPi-2alpha, NaPi-2beta and NaPi-2gamma) from a rat kidney library. NaPi-2alpha cDNA encodes 337 amino acids which have high homology to the N-terminal half of NaPi-2 containing three transmembrane domains. NaPi-2beta encodes 327 amino acids which are identical to the N-terminal region of NaPi-2 containing four transmembrane domains, whereas the 146 amino acids in the C-terminal region are completely different. In contrast, NaPi-2gamma encodes 268 amino acids which are identical to the C-terminal half of NaPi-2. An analysis of phage and cosmid clones indicated that the three related proteins were produced by alternative splicing in the NaPi-2 gene. In a rabbit reticulocyte lysate system, NaPi-2alpha, beta and gamma were found to be 36, 36 and 29 kDa polypeptides, respectively. NaPi-2alpha and NaPi-2gamma were glycosylated and revealed to be 45 and 35 kDa proteins, respectively. A functional analysis demonstrated that NaPi-2gamma and alpha markedly inhibited NaPi-2 activity in Xenopus oocytes. The results suggest that these short isoforms may function as a dominant-negative inhibitor of the full-length transporter.

Animals↗

Functional analysis of the individual oligosaccharide chains of sendai virus fusion protein.

The roles of N-linked glycosylation in the intracellular transport and fusion activity of the Sendai virus fusion (F) protein were studied. Each of three potential glycosylation motifs (designated g1, g2, and g3) in the F protein was mutated separately or in combination with the other sites. When the mutant F proteins were transiently expressed in COS cells, they showed significant changes in electrophoretic mobility, indicating that all three motifs in the F protein are glycosylated. Glycosylation-defective mutants which lacked the g2-oligosaccharide chain showed decreased immunoreactivity with a monoclonal antibody specific for the native conformation and were inefficiently transported to the cell surface. Such mutants, with the exception of a double mutant lacking g1 and g2-oligosaccharide chains, were also not able to induce syncytia formation when cells expressing them plus the hemagglutinin-neuraminidase protein were treated with trypsin. Mutations at the other glycosylation sites did not significantly affect the immunoreactivity with the monoclonal antibody or the efficiency of intracellular transport of the F protein. These results indicate that the N-linked oligosaccharide chain attached at g2 is important for efficient intracellular transport and for the fusion activity of the F protein.

Animals↗

Neurovascular decompression for idiopathic tarsal tunnel syndrome: technical note.

OBJECTIVE: The surgical outcome of idiopathic tarsal tunnel syndrome (TTS) is reported to be worse than that attributable to ganglion, tarsal coalition, or tumour, and therefore further development in the surgical treatment for idiopathic TTS is considered to be necessary. Here the efficacy of neurovascular decompression for patients with idiopathic TTS is evaluated. METHODS: Twelve feet from nine patients with idiopathic TTS were treated. The patients were aged 52-78 years (mean 64.6 years), and all of them complained of pain or dysaesthesia of the sole of the foot. The posterior tibial nerve was freed from the attached arteriovenous complex (posterior tibial artery and veins). The dissected nerve had a flattened appearance in all of the patients, suggesting nerve compression by the adjacent arteriovenous complex and superficially by the flexor retinaculum. A graft of fat was inserted as both a cushion and an antiadhesive between the vessels and the nerve to achieve neurovascular decompression. RESULTS: Patients on whom neurovascular decompression was performed had resolution or lessening of symptoms in their feet. Neither wound infection nor recurrence of symptoms was found during the follow up period (mean 26.8 months). CONCLUSION: Neurovascular compression syndrome plays a part in idiopathic TTS, and adding neurovascular decompression to resection of the flexor retinaculum is effective.

Aged↗

Clinicopathological study of intracranial fusiform and dolichoectatic aneurysms : insight on the mechanism of growth.

BACKGROUND AND PURPOSE: Intracranial fusiform aneurysms can be divided into 2 clinically different subtypes: acute dissecting aneurysms and chronic fusiform or dolichoectatic aneurysms. Of these 2, the natural history and growth mechanism of chronic fusiform aneurysms remains unknown. METHODS: A consecutive series of 16 patients with chronic fusiform aneurysms was studied retrospectively to clarify patient clinical and neuroradiological features. Aneurysm tissues were obtained from 8 cases and were examined to identify histological features that could correspond to the radiological findings. RESULTS: Four histological features were found: (1) fragmentation of internal elastic lamina (IEL), (2) neoangiogenesis within the thickened intima, (3) intramural hemorrhage (IMH) and thrombus formation, and (4) repetitive intramural hemorrhages from the newly formed vessels within thrombus. IEL fragmentation was found in all cases, which suggests that this change may be one of the earliest processes of aneurysm formation. MRI or CT detected IMH, and marked contrast enhancement of the inside of the aneurysm wall (CEI) on MRI corresponded well with intimal thickening. Eight of 9 symptomatic cases but none of 7 asymptomatic cases presented with both radiological features. CONCLUSIONS: Data suggest that chronic fusiform aneurysms are progressive lesions that start with IEL fragmentation. Formation of IMH seems to be a critical event necessary for lesions to become symptomatic and progress, and this can be monitored on MRI. Knowledge of this possible mechanism of progression and corresponding MRI characteristics could help determine timing of surgical intervention.

Adult↗

Estimation of the lethal toluene concentration from the accidental death of painting workers.

To determine the potentially lethal level of thinner concentration in the air, we measured the concentration of toluene in the blood and others of three patients who suffered severe acute thinner intoxication between 4 January 1996 and 21 April 1997 in Ube city. The concentration of toluene in blood were 30.2 mg/L in died patient, and 13.7 mg/L and 17.5 mg/L in recovered patients, respectively. By extrapolation from the results of our previous toxicokinetic research on toluene poisoning in anesthetized dogs, the fatal concentration of toluene was estimated to be approximately 1800 to 2000 ppm for 1-hour exposure.

Accidents, Occupational↗

[Intraoperative autologous blood transfusion was effective in a massive blood loss during living-related donor liver transplantation].

We have experienced massive blood loss (> 80,000 g) during living-related donor liver transplantation (LRDLT) of a 14-year old girl with biliary atresia. As available homologous blood was not sufficient, we transfused autologous blood (13,400 ml) during operation. Although immunosuppressant was administered to the patient, severe infection did not occur for 10 days after the operation. Cold ischemia time of the graft liver was about 16 hr, but her postoperative liver function was well-maintained. The case suggests that intraoperative autologus blood transfusion is effective if homologous blood is insufficient during LRDLT.

Adolescent↗

Secondary hyperparathyroidism and phosphate sensing in parathyroid glands.

Retention of inorganic phosphate (Pi) and associated hyperphosphatemia are important development of hyperparathyroidism secondary to renal failure. The beneficial effect of a low-Pi diet in the prevention of hyperparathyroidism can be attributed to the decrease in PTH secretion. This effect of Pi may be mediated by specific molecules in the parathyroid cell membrane. A complementary DNA encoding a Na(+)-Pi co-transporter, termed rat PiT-1, has been isolated from rat parathyroid. The amount of PiT-1 mRNA in the parathyroid is controlled by vitamin D and dietary Pi, which are the most important regulators of PTH secretion. The parathyroid Pi transporter may mediate the effects of extracellular Pi and PTH secretion in secondary hyperparathyroidism. In this study, we focus on the function of Na/Pi co-transporters in the parathyroid glands as inorganic Pi sensor.

Animals↗

Regulation of intestinal Na+-dependent phosphate co-transporters by a low-phosphate diet and 1,25-dihydroxyvitamin D3.

In a study of the rat intestinal P(i) transport system, an activator protein for rat Na/P(i) co-transport system (PiUS) was isolated and characterized. We also investigated the effects of restriction of vitamin D and P(i) (two of the most important physiological and pathophysiological regulators of P(i) absorption in the small intestine) on intestinal P(i) transport activity and the expression of Na/P(i) co-transporters that are expressed in rat small intestine. Rat PiUS encodes a 424-residue protein with a calculated molecular mass of 51463 Da. The microinjection of rat PiUS into Xenopus oocytes markedly stimulated Na(+)-dependent P(i) co-transport activity. In rats fed with a low-P(i) diet, Na(+)-dependent P(i) co-transport activity was increased approx. 2-fold compared with that of rats fed a normal P(i) diet. Kinetic studies demonstrated that this increased activity was due to an elevation of V(max) but not K(m). The PiUS mRNA levels showed an approximate doubling in the rats fed with the low-P(i) diet compared with those fed with the normal P(i) diet. In addition, after the administration of 1, 25-dihydroxyvitamin D(3) [1,25-(OH)(2)D(3)] to vitamin D-deficient animals, the P(i) uptake was significantly increased in the Na(+)-dependent component in the brush border membrane vesicle (BBMV) at 24 and 48 h. In addition, we found a further high-affinity Na/P(i) co-transport system in the BBMV isolated from the vitamin D-replete animals. The levels of type III Na/P(i) co-transporter PiT-2 mRNA were increased 24 and 48 h after 1,25-(OH)(2)D(3) administration to vitamin D-deficient animals, whereas PiUS and the type IIb Na/P(i) co-transporter mRNA levels were unchanged. In conclusion, we first cloned a rat activator protein, PiUS, and then studied its role along with that of other type III Na/P(i) co-transporters. PiUS and PiT-2 might be important components in the regulation of the intestinal P(i) transport system by P(i) restriction and 1,25-(OH)(2)D(3).

Amino Acid Sequence↗

Identification of an amino acid transporter associated with the cystinuria-related type II membrane glycoprotein.

We identified an amino acid transporter that is associated with the cystinuria-related type II membrane glycoprotein, rBAT (related to b(0,+) amino acid transporter). The transporter designated BAT1 (b(0, +)-type amino acid transporter 1) from rat kidney was found to be structurally related to recently identified amino acid transporters for system L, system y(+)L, and system x(-)C, which are linked, via a disulfide bond, to the other type II membrane glycoprotein, 4F2hc (4F2 heavy chain). In the nonreducing condition, a 125-kDa band, which seems to correspond to the heterodimeric complex of BAT1 and rBAT, was detected in rat kidney with anti-BAT1 antibody. The band was shifted to 41 kDa in the reducing condition, confirming that BAT1 and rBAT are linked via a disulfide bond. The BAT1 and rBAT proteins were shown to be colocalized in the apical membrane of the renal proximal tubules where massive cystine transport had been proposed. When expressed in COS-7 cells with rBAT, but not with 4F2hc, BAT1 exhibited a Na(+)-independent transport of cystine as well as basic and neutral amino acids with the properties of system b(0,+). The results from the present investigation were used to establish a family of amino acid transporters associated with type II membrane glycoproteins.

ATP-Binding Cassette Transporters↗