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Biomedical subjects

T Hirata

Publications and source records attributed to T Hirata.

At least 181 records · Page 10Linked to original sources

Impaired healing of gastric lesions in streptozotocin-induced diabetic rats: effect of basic fibroblast growth factor.

We examined the influence of diabetes on the healing of HCI-induced gastric lesions and the healing promoting effect of basic fibroblast growth factor (bFGF) on these lesions under diabetic conditions induced in rats by streptozotocin (70 mg/kg, i.p.). The experiments were performed using 2-wk streptozocin-diabetic rats with blood glucose levels of >300 mg/dl. After 18 hr fasting, these animals were given 1 ml of 0.6 N HCl by gavage, and 1 hr later they were fed normally before being killed on various days after HCI treatment. Recombinant human basic fibroblast growth factor (acid resistant recombinant human basic fibroblast growth factor mutein CS-23: 10 to 1000 ng/kg x 2, p.o.) or insulin (4 U/rat x 1, s.c.) was given 5 days after HCl treatment. Gastric lesions induced by HCI healed to quiescent state within 5 days both macro- and microscopically. Diabetic conditions did not affect the development of HCI-induced gastric lesions but significantly delayed the healing of these lesions. Daily administration of insulin returned high blood glucose levels to within normal ranges (120-140 mg/dl) and significantly antagonized the delayed healing of these lesions. The delayed healing in diabetic rats was also significantly promoted by recombinant human basic fibroblast growth factor (>300 ng/kg x 2) without any effect on blood glucose level. In normal rats, the mucosal levels of bFGF increased significantly in response to gastric injury at 3 days after HCI treatment. The mucosal bFGF levels in streptozotocin-diabetic rats were significantly lower under basal conditions before HCI treatment and did not increase after injury, yet such dysregulation of bFGF production was partially restored by insulin treatment. rhbFGF even at 1000 ng/kg had no effect on gastric acid secretion in either normal or streptozotocin-diabetic rats. These results suggest that diabetic conditions have deleterious influences on the healing of acute gastric lesions in both an insulin- and bFGF-sensitive manner, and that the administration of exogenous bFGF antagonizes the delayed healing of gastric lesions observed in diabetic animals.

Animals↗

Thymic interdigitating cells express thioredoxin (TRX/ADF): an immunohistochemical study of 82 thymus and thymoma samples.

Thymic ID cells are involved in the differentiation of mature T cells which are resistant against apoptosis. TRX/ADF is a potent thiol-related reducing agent, acts as a redox regulator, and it can attenuate the induction of apoptosis of T lineage lymphocytes. In the present study, 42 thymoma-free thymus and 40 thymoma samples were examined to identify the expression of TRX/ADF in human thymic tissue. TRX/ADF high-producer (TRXh) cells with cytoplasmic protrusions were found distributed in the thymic medulla. These TRXh cells were negative for CD3, a lymphocyte marker, keratin, an epithelial cell marker, and CD68 or lysozyme, macrophage/monocyte markers, but were positive for S100 protein and HLA-DR complex. Our results revealed that the TRXh cells in the thymic medulla were ID cells. As TRX/ADF has an important and fundamental role in cellular responses acting against oxidative stress, TRX/ADF may provide an explanation of cellular interaction between the medullary ID cells and the mature T cells.

Adolescent↗

[Arterial-venous carbon dioxide tension difference after hypothermic cardiopulmonary bypass].

Arterial-venous carbon dioxide tension difference (Pv-aCO2) is known to become high after severe hemorrhage shock and resuscitation. We hypothesized that Pv-aCO2 might be high after cardiac surgery because of the oxygen debt occurred during hypothermic cardiopulmonary bypass (CPB). Blood pressure, cardiac index, hemoglobin, the arterial and mixed venous blood gases were repeatedly measured every 6 hours for 24 hours following cardiac surgery in 60 adult patients who underwent hypothermic CPB. Immediately after the surgery, Pv-aCO2 was extremely high, then gradually decreased to within normal ranges 12 hours later (8.0 +/- 2.9 mmHg vs 5.9 +/- 3.1 mmHg. p < 0.01). Factors which significantly correlated to Pv-aCO2 were cardiac index, oxygen delivery, minimum rectal temperature and duration of CPB. Oxygen debt during hypothermic CPB might cause significantly high Pv-aDO2. At least 12 hours were necessary to recover from anaerobic status to physiological condition.

Adult↗

Postoperative inflammatory reactions to sealed Dracon prostheses: a comparison of Gelseal and Hemashield.

OBJECTIVE: The purpose of this study was to assess and compare inflammatory reactions to two types of sealed vascular prostheses used in the repair of abdominal aortic aneurysm. EXPERIMENTAL DESIGN: Randomized prospective study with a follow-up period of 21 days. SETTING: University hospital study. PATIENTS: Sixty patients admitted for elective abdominal aortic aneurysm repair. INTERVENTION: Each patient underwent repair of abdominal aortic aneurysm with either a gelatin-sealed knitted Dacron prosthesis (Gelseal, Vascutek, n = 30) or a collagen-sealed woven Dacron prosthesis (Hemashield, Meadox Medicals, n = 30). MEASURES: As indicators of the presence of inflammation, the peripheral blood cell count, platelet count, and plasma C-reactive protein (CRP) concentration were determined in each patient on postoperative days (PODs) 1, 7, 14 and 21. Body temperature was measured every 8 hours. RESULTS: Patients in both groups revealed a low-grade fever and leukocytosis during the first 7 PODs. Significantly higher leukocyte counts were demonstrated in the Gelseal group on PODs 7 and 14. However, no difference in the leukocyte count, CRP concentration, or body temperature existed between the two groups on POD 21. Biphasis changes in the platelet count were observed in both groups. No complications were encountered. CONCLUSION: The Gelseal prosthesis was associated with higher inflammatory response during the second week following implantation, but this difference had resolved by POD 21. This finding may reflect an inflammatory reaction against impregnated gelatin.

Aged↗

[A case of far-advanced gastric cancer treated with neoadjuvant combination chemotherapy of UFT, low-dose CDDP and leucovorin, followed by subtotal gastrectomy with curative intent].

We herein present a case of a 70-year-old man with the tentative diagnosis of far-advanced gastric cancer supposed to be beyond surgical intervention. Neoadjuvant chemotherapy enabled us to perform subtotal gastrectomy with curative intent. The man was admitted to our hospital with the chief complaint of poor appetite. Because preoperative examinations revealed a mass adjacent to the portal vein and common bile duct, which was suspected to be lymphnode metastasis or gastric cancer directly invading those vital structures, 4 weeks of neoadjuvant combination chemotherapy (NACC) (CDDP 10 mg/body, day 1 through day 5/week, UFT 600 mg/body, every day, Leucovorin 15 mg/body, every day) was given with resultant curative resection of the tumor one month after completion of NACC.

Aged↗

Acute aortic dissection without intimal tear.

A case of acute aortic dissection without intimal tear is reported. A 68-year-old woman with acute onset of Stanford type-B aortic dissection was admitted. Because of progressive anemia and pleural leakage, an operation was performed. False lumen of the descending thoracic aorta was occupied with fresh hematoma, but no sign of an intimal defect was found. Although aortic dissection without intimal tear has been reported via angiography, CT scan, MRI, and autopsy, surgically confirmed cases of this type of dissection have been rarely reported.

Acute Disease↗

Gastric hyperemic response during vagally mediated acid secretion by TRH analog in rats.

The mechanisms of gastric hyperemic response during vagally mediated acid secretion induced by YM-14673, an analog of thyrotropin-releasing hormone, were investigated in urethane-anesthetized rats. The stomach was mounted on an ex vivo chamber and perfused with saline, and gastric mucosal blood flow (GMBF) was measured using a laser Doppler flowmeter, simultaneously with acid secretion. The i.v. injection of YM-14673 (0.1 approximately 1 mg/kg) increased both GMBF and acid secretion in a dose-dependent manner, and these responses persisted during a 90-min test period. The increases in GMBF and acid secretion induced by YM-14673 (0.3 mg/kg) were totally abolished by either bilateral vagotomy or atropine. Sensory ablation by capsaicin also significantly attenuated GMBF response without affecting acid secretion. On the other hand, N(G)-nitro-L-arginine methyl ester (L-NAME), but not D-NAME, significantly attenuated the increase in GMBF in an L-arginine-sensitive manner, although acid secretion was slightly augmented; in particular, gastric hyperemic response during the first 30 min (early period) was almost totally abolished. In contrast, omeprazole significantly attenuated GMBF response only in the late period, although it completely inhibited acid secretion in response to YM-14673. Combined treatment of omeprazole and L-NAME totally abolished hyperemic responses induced by YM-14673 during the test period. YM-14673 significantly elevated the release of nitrite and nitrate into the gastric lumen, and this response was inhibited by either atropine or L-NAME. These results suggest that YM-14673 increases GMBF as well as acid secretion, mediated by vagal-cholinergic pathways, and that gastric hyperemia is further regulated by two distinct mechanisms. The response in the early period is independent of acid secretion and mediated mainly by nitric oxide, whereas that in the later period occurs in association with acid secretion and may be mediated by nitric oxide and sensory neurons.

Animals↗

Effects of Euro-Collins, University of Wisconsin, and new extracellular-type trehalase-containing Kyoto solutions in an ex vivo rat lung preservation model.

BACKGROUND: We have previously reported the effects of trehalose-based extracellular-type Kyoto (ET-K) solution in lung preservation. Now, we have developed a new ET-K solution by adding three substances--N-acetyl cysteine, dibutyryl cyclic AMP, and nitroglycerin, to ET-K solution. We studied the effects of new ET-K solution in lung preservation, and compare it with Euro-Collins (EC) and University of Wisconsin (UW) solutions using an ex vivo rat reperfusion model. METHODS: The perfusion circuit was initiated by 30 ml of fresh mixed venous blood obtained from three haparinized rats. By means of a double-head roller pump, the blood passed from the venous blood reservoir through the pulmonary artery to be perfused in the examined lung. The lung effluent was returned at the same flow rate to the deoxygenator fresh lung. Four experimental groups were allocated. In group 1 (fresh group, n=6), lung was flushed with saline and reperfused immediately. In the other groups (group 2: new ET-K group, n=6; group 3: UW group, n=6; and group 4: EC group, n=6), lung was flushed with the new ET-K and prostanglandin E1 (PGE1), UW and PGE1, and EC and PGE1, respectively. After 17-hr preservation, the preserved lung was reperfused. RESULTS: In all six animals of the EC group, ventilation of the experimental lung was discontinued at 20 min after reperfusion because of the exudate in the endotracheal tube that resulted from pulmonary edema. The shunt fraction, pulmonary arterial pressure, and peak inspiratory pressure in the new ET-K and UW groups were significantly better than those in the EC group, but were almost equal to those in the fresh group. CONCLUSION: The postpreservation pulmonary functions with the new ET-K solution were better than those with the EC solution, and were equal to those with the UW solution. This new solution is expected to contribute to the increase in donor lungs for clinical lung transplantation. In addition, this ex vivo rat reperfusion model is simple and highly reliable, and can be widely used in the studies of pulmonary preservation.

Adenosine↗

Translocation of protein kinase C-alpha, delta and epsilon isoforms in ischemic rat heart.

To explore the spatial and temporal localization of PKC isoforms during ischemia, we quantified PKC isoforms in the subcellular fractions in perfused rat heart by immunoblotting using specific antibodies against PKC isoforms. PKCs-alpha and epsilon translocated from the 100000 x g supernatant (S, cytosolic) fraction to the 1000 x g pellet (PI, nucleus-myofibril) and the 1000-100000 x g pellet (P2, membrane) fractions during 5-40 min of ischemia. PKC-delta redistributed from the P2 to the S fraction. A 50-kDa fragment of PKC-alpha appeared during ischemia possibly through calpain action. Immunohistochemical observations showed the different localizations of PKC-alpha, delta, and epsilon in the myocytes. The PKC assay displayed high basal levels of Ca(2+)-independent PKC, the activation of Ca(2+)-dependent PKC in the P1 and P2 fractions, and the activation of Ca(2+)-independent PKC in the P1 fraction after 20 min of ischemia. These observations show that ischemia induces different patterns of translocation of the three PKC isoforms, suggesting differences in their roles.

Animals↗

Identification of plexin family molecules in mice.

By screening of E17.5 mouse brain cDNA libraries, we isolated two cDNAs encoding new plexin-like proteins. Sequencing revealed that these two proteins were type 1 membrane proteins which showed over 60% identity at the amino acid level to mouse plexin 1. Moreover, putative extracellular segments of these two proteins had three repeats of a cysteine-rich domain which is a common motif for plexin proteins. Thus, we named these two proteins mouse plexin 2 and mouse plexin 3. We obtained mouse plexin 3 cDNA clones in which a part of protein-coding region was deleted. Also, Northern blot analysis showed molecular heterogeneity in mouse plexin 2 mRNAs. These findings indicate that in the mouse, plexins comprise a molecular family (the plexin family).

Alternative Splicing↗

Identification of a neuronal cell surface molecule, plexin, in mice.

We searched for mouse homologues of the cell adhesion protein plexin which was originally found in Xenopus, and obtained a cDNA encoding a plexin-like protein. We referred to this protein as mouse plexin 1. The overall amino acid identity between mouse plexin 1 and Xenopus plexin was 84%. As in the Xenopus plexin, the extracellular segment of mouse plexin 1 protein possessed three cysteine-rich domains which showed significant homology with the cysteine-rich domain of the c-Met proto-oncogene protein product (c-Met protein) and Met-like receptor protein tyrosine kinases. Northern blot analysis indicated that mouse plexin 1 was predominantly expressed in the brain.

Amino Acid Sequence↗

Two thromboxane A2 receptor isoforms in human platelets. Opposite coupling to adenylyl cyclase with different sensitivity to Arg60 to Leu mutation.

Thromboxane A2 (TXA2) receptor is a key molecule in hemostasis as its abnormality leads to bleeding disorders. Two isoforms of the human TXA2 receptor have been cloned; one from placenta and the other from endothelium, here referred to as TXR alpha and TXR beta, respectively. These isoforms differ only in their carboxyl-terminal tails. We report that both isoforms are present in human platelets. The two isoforms expressed in cultured cells show similar ligand binding characteristics and phospholipase C (PLC) activation but oppositely regulate adenylyl cyclase activity; TXR alpha activates adenylyl cyclase, while TXR beta inhibits it. The Arg60 to Leu mutant of TXR alpha, which has been shown to impair PLC activation (Hirata, T., A. Kakizuka, F. Ushikubi, I. Fuse, M. Okuma, and S. Narumiya. 1994. J. Clin. Invest. 94: 1662-1667), also impairs adenylyl cyclase stimulation, whereas that of TXR beta retains its activity to inhibit adenylyl cyclase. These findings suggest that the pathway linked to adenylyl cyclase inhibition might be involved in some of the TXA2-induced platelet responses such as shape change and phospholipase A2 activation which remain unaffected in the patients with this mutation.

Adenylyl Cyclases↗

Positional cues that are strictly localized in the telencephalon induce preferential growth of mitral cell axons.

In mice, mitral cells are the major efferent neurons of the main olfactory bulb and elongate axons into a very narrow part of the telencephalon to form a fiber bundle referred to as the lateral olfactory tract (LOT). To clarify the mechanisms responsible for guidance of mitral cell axons along this particular pathway, we co-cultured mouse embryo main olfactory bulbs with the telencephalons, and analyzed the pathways taken by mitral cell axons. Ingrowth of mitral cell axons into the telencephalon was observed in those co-cultures in which the olfactory bulbs had been exactly combined to their normal pathway (the LOT position) of the telencephalon. The axons grew preferentially along the LOT position, and formed a LOT-like fiber bundle. When the olfactory bulbs were grafted at positions apart from their normal pathway, however, no mitral cell axons grew into the telencephalon. Neocortical fragments combined with the telencephalon projected fibers into the telencephalon in random directions. These results suggest that the LOT position of the telencephalon offers a guiding pathway for mitral cell axons and that guiding cues for mitral cell axons are extremely localized.

Animals↗

Inflammatory reactions after vascular prosthesis implantation: a comparison of gelatin-sealed and unsealed Dacron prostheses.

Despite widespread use of the gelatin-sealed knitted Dacron prosthesis (GDP) in clinical practice owing to its zero porosity, the biological impacts of this graft are still controversial. We conducted a randomized controlled study on 50 patients undergoing abdominal aortic aneurysm repair to evaluate the inflammatory reaction to GDP (n = 25) and unsealed knitted Dacron prostheses (UDP, n = 25). There were no significant differences in the mean age, size of the aneurysm, operative time, blood loss, or transfusion requirements between the GDP and UDP groups. During the first 7 postoperative days (PODs), slight fever and leukocytosis were noticed in both groups. Significant differences in maximum body temperature, leukocyte count, and plasma C-reactive protein concentration were observed between the GDP and UDP groups on POD 14:37.2 +/- 0.5 degrees C vs 36.9 +/- 0.3 degrees C (P = 0.019), 8,151 +/- 1,788/microliters vs 6,914 +/- 1,501/microliters (P = 0.015), and 32.6 +/- 27.5 mg/l vs 19.0 +/- 15.8 mg/l (P = 0.048), respectively. By POD 21, however, there were no detectable differences in these variables. Thus, we concluded that GDP caused an inflammatory reaction in the 2nd week after implantation, but ultimately there were no significant differences from UDP by the 3rd week.

Aged↗