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Biomedical subjects

M Sakaguchi

Publications and source records attributed to M Sakaguchi.

At least 253 records · Page 14Linked to original sources

Two regulation points for differentiation in the cell cycle of human megakaryocytes.

To examine the relationship between cell cycle progression and differentiation in megakaryocytes, variances in the cell cycle during PMA (phorbol 12-myristate-13-acetate)-induced differentiation were analysed in synchronized growing CMK cells. The cells stimulated with PMA in early S phase showed cell cycle arrest in G2 phase. In addition, the cells stimulated with PMA in early G1 phase showed cell cycle arrest in late G1. The expression of gpIIb/IIIa, megakaryocytic differentiation marker, was markedly induced in G2 phase when the cells were stimulated in early S phase, and was also induced in late G1 phase when cells were stimulated in early G1 phase. Therefore, the induction of gpIIb/IIIa expression seems to be associated with cell cycle blockage in both G2 and late G1. Expression of the transcription factor GATA-1 in cells stimulated in early S phase was much higher than that in controls at G2 phase. Furthermore, GATA-1 expression in cells stimulated in early G1 tended to be higher than that in controls at late G1. These periods corresponded to the time that the cell cycle arrest and gpIIb/IIIa expression were induced by PMA. These results suggest that the cell cycle in human megakaryocytic lineage cells may have two regulation points for differentiation.

Base Sequence↗

Splenectomy-reduced hepatic injury induced by ischemia/reperfusion in the rat.

In the present study, we investigated the role of the spleen in experimental hepatic ischemia/reperfusion in the rat. After a 90-min period of ischemia in the left and middle hepatic lobes, the ischemia was released and the liver was reperfused for up to 24 h. Plasma alanine aminotransferase reached a peak 3 h after the onset of reperfusion, and gradually decreased thereafter. A histological examination revealed evidence of hepatocellular necrosis and degeneration, especially 24 h after the onset of reperfusion. In addition, there was a noticeable accumulation of polymorphonuclear cells in the liver following ischemia/reperfusion. A splenectomy performed just prior to ischemia/reperfusion reduced both biochemical and histological hepatocellular injury. The number of polymorphonuclear cells in the liver following ischemia/reperfusion was significantly reduced in rats subjected to splenectomy, suggesting that the increase in polymorphonuclear cells may contribute to liver injury. The number of mononuclear cells also increased in the marginal zones of the spleen following ischemia/reperfusion, and appeared to be derived from the splenic monocyte/macrophage population, based on immunohistochemical studies. The spleen plays an important role in the pathogenesis of hepatic ischemia/reperfusion injury and the splenic monocyte/ macrophage population contributes to liver damage.

Alanine Transaminase↗

Diurnal variation in intragastric pH in children with and without peptic ulcers.

Diurnal variation in intragastric pH in children with peptic ulcers has not been previously reported. Therefore, we monitored intragastric pH during a 24-h period in 82 subjects (10 children with gastric ulcers, 9 children with duodenal ulcers, 58 non-ulcer (comparison group) children, and 5 healthy adults) using a monopolar glass pH electrode. The percent of readings below pH 2, 3, 4, and 5 for each subject was calculated and compared between the comparison group and the two ulcer groups using means and slopes (i.e. changes in percent with age for each group) of percent readings for each pH analysis. In the comparison group children, gastric acidity increased with age and reached adult levels by 14 y. Mean readings for all pH analyses in gastric ulcer children were lower than those in age-adjusted comparison children (p < 0.05). The slopes of the relationships between age and the percent time below any pH for the gastric ulcer group were different from those in the comparison group (p < 0.05) and were negative for all pH analyses. The mean time below pH 2 in children with duodenal ulcers was greater than that in age-adjusted comparison children (p = 0.002). The slope of the relationship between age and the percent time below pH 2 in the duodenal ulcer group was different from that in the comparison group (p < 0.05). Gastric acidity in children with primary gastric ulcers was reduced during childhood, but in children with primary duodenal ulcer, gastric acidity was at or above adult levels.

Adolescent↗

Inhibition of collagen-induced platelet aggregation in Japanese black cattle with inherited platelet disorder, Chediak-Higashi syndrome.

Aggregation properties of platelets were examined in Japanese Black cattle with Chediak-Higashi syndrome (CHS) and normal control cattle. Platelet aggregation induced by collagen was decreased in platelets of the cattle with CHS, but not ADP (10-20 microM), thrombin (0.5-1.0 U/ml) and phorbol-12-myristate 13-acetate (PMA, 3.2 microM). The aggregation response induced by collagen in CHS platelets lacks the change in shape which usually occurs in normal platelets. Simultaneous stimulation by collagen (10 micrograms/ml) + ADP (10 microM) is effective in restoring collagen-induced aggregating response in CHS platelet, although pretreatment of ADP (10 microM) could not restore the collagen (10 micrograms/ml)-induced aggregating response, suggesting that there is a certain threshold of stimulation intensity above which collagen-induced aggregation of CHS platelet can begin. Control normal platelets, previously exposed to ADP (10 microM) and collagen (10 micrograms/ml), showed no further response to exposure to a third aggregating agent (arachidonic acid, 5 mM). On the other hand, the final agent was able to elicit aggregating responses in CHS platelets, suggesting that the arachidonate aggregating system may be suppressed in CHS cattle, but fully activated in control animals. Furthermore, normal platelets showed a significant decrease in aggregating response to collagen when pretreated with a cyclooxygenase inhibitor, indomethacin (10(-5) M), whereas CHS platelet was insensitive to indomethacin. This indomethacin-treated normal platelet mimicked the CHS collagen-induced aggregation pattern. These data suggest that a signal transduction process from receptor-operated events to arachidonate metabolism is suppressed in collagen-induced CHS platelet aggregation.

Adenosine Diphosphate↗

The effects of xylazine on plasma concentrations of growth hormone, insulin-like growth factor-I, glucose and insulin in calves.

The purpose of the present study was to examine the responses of plasma growth hormone (GH) and insulin-like growth factor-I (IGF-I) levels to intravenous injection of xylazine in female dairy calves. Xylazine (0.05, 0.15 and 0.30 mg/kg body wt., i.v.) injections induced a significant dose-dependent increase in plasma GH level within 30 min. After plasma GH levels reached peaks, GH concentrations began to decrease immediately and they returned to control levels 1 h after xylazine injection. Plasma IGF-I concentration tended to be suppressed by xylazine treatment. Xylazine induced a significant dose-dependent increase in plasma glucose for 3.5 to 5.5 h after the treatments. Xylazine also induced a significant decrease in plasma insulin level within 30 min after treatments. The present data suggested that xylazine stimulates GH release in cattle.

Analgesics↗

Effects of atipamezole, an alpha 2-adrenergic antagonist, and somatostatin on xylazine-induced growth hormone release in calves.

In order to clarify the mechanism of xylazine-induced GH release, we investigated the effects of atipamezole, a selective alpha 2-adrenergic antagonist, and somatostatin (SRIF) on xylazine-stimulated GH release in calves. Xylazine injection (0.30 mg/kg BW, iv) induced a rapid increase in the GH concentration. When atipamezole was used in combination with xylazine, it blunted the increase in the plasma GH concentration induced by the xylazine injection. The GH levels at 15-50 min after the simultaneous injection of xylazine and atipamezole were significantly (P < 0.05) lower than the corresponding values in the animals given xylazine alone. The area under the GH response curve for 120 min after the simultaneous injection of xylazine and atipamezole was significantly (P < 0.05) smaller than that for the xylazine alone. A series of five intravenous injections of 1 mg of SRIF at 10-min intervals also blunted xylazine-stimulated GH release. Atipamezole partially suppressed xylazine-induced hyperglycemia, but SRIF completely suppressed the hyperglycemia for the first 60 min after the xylazine injection and the suppression by SRIF was stronger than that by atipamezole. On the other hand, both atipamezole and SRIF failed to blunt xylazine-induced hypoinsulinemia. The present results suggest that xylazine stimulates GH release via the alpha 2-adrenergic pathway in cattle, but the mechanism of xylazine-induced hyperglycemia remains to be determined.

Adrenergic alpha-Antagonists↗

[CA19-9 producing mixed gonadal germ-cell tumor in undescended testis located in abdomen. A case report].

A rare case of CA19-9 producing tumor in undescended testis was presented. A forty-three year old man visited to our hospital with a chief complaint of left flank pain. Serum tumor markers (AFP, beta-HCG, and CA19-9) were elevated. Abdominal CT scan demonstrated large solid mass with multilocular cysts were capsulated. The tumor resection was performed after 3 courses of CEB (Carboplatin, Etoposide, and Bieomycin) chemotherapy. Macroscopically, the tumor was consisted of necrotic mass and multilocular cysts. The tumor size was 25 x 8 x 5 cm and weight was 1000 g. Microscopically, the large part of tumor was necrotic due to chemotherapy, and the teratoma component which was consist of neural, muscular, and digestive tissue was seen in some area. In conclusion, this is a rare case of mixed germ-cell tumor in undescended testis located in abdomen.

Abdomen↗

Anesthesia induced in pigs by use of a combination of medetomidine, butorphanol, and ketamine and its reversal by administration of atipamezole.

OBJECTIVE: To develop an IM administrable anesthetic combination for pigs. DESIGN: Use of a combination of atropine, medetomidine, butorphanol, and ketamine (MB-K) was evaluated as an anesthetic regimen and compared with that of a combination of atropine, xylazine, butorphanol, and ketamine (XB-K). Cardiorespiratory effects of MB-K combination and use of atipamezole as a means of reversing anesthesia induced by MB-K were examined. ANIMALS: 18 castrated, mixed-breed, specific-pathogenfree pigs, aged 8 to 15 (mean, 12.1) weeks and weighing 14.5 to 26.0 (mean, 19.6) kg. were studied. PROCEDURE: Dosages of drugs used in this study were atropine, 25 micrograms/kg of body weight; medetomidine, 80 micrograms/kg; xylazine, 2 mg/kg; butorphanol, 200 micrograms/kg; ketamine, 10 mg/kg; and atipamezole, 240 micrograms/kg. RESULTS: MB-K combination proved to be more effective than XB-K combination as an anesthetic combination. After quick and smooth induction by IM administration, MB-K-induced anesthesia was sustained for 98.8 +/- 22.5 minutes (mean +/- SD, 47.4 +/- 16.5 minutes by XB-K) with accompanying muscular relaxation (91 +/- 18 minutes) and loss of pedal (82 +/- 24 minutes) and laryngeal (75 +/- 19 minutes) reflexes. Loss of these reflexes was of significantly longer duration than the loss induced by XB-K, enabled tracheal intubation, and, thus, supported major surgery for at least 30 minutes after induction. Recovery from MB-K-induced anesthesia was smooth. MB-K combination had a slight stimulative effect on cardiovascular status, and a significant depressant effect on blood gas and acid-base status, but these effects were within biologically acceptable limits. Oxygen consumption of pigs under MB-K-induced anesthesia decreased significantly. MB-K-induced anesthesia could be effectively and quickly reversed by IM or IV administration of atipamezole. CONCLUSIONS: The combination of medetomidine, butorphanol, and ketamine induces excellent surgical anesthesia in pigs, and results in moderate cardiorespiratory effects. A great advantage of the anesthetic regimen is that it can be effectively and quickly reversed by atipamezole. CLINICAL RELEVANCE: Medetomidine, butorphanol, and ketamine-induced anesthesia is available for short-term major surgery in pigs.

Adrenergic alpha-Antagonists↗

Pathogenetic mechanism and prevalence of the stable atlantoaxial subluxation in rheumatoid arthritis.

OBJECTIVE: To study the pathogenetic mechanisms responsible for and prevalence of stable atlantoaxial subluxation (AAS). METHODS: Lateral view cervical spine radiographs during flexion and extension were studied in 262 patients with rheumatoid arthritis (RA). RESULTS: AAS was found in 130 patients, 42 (32%) of whom had a stable deformity; in a population based subseries, stable AAS was seen in 16% of the patients with ASS. Atlantoaxial impaction (AAI) was diagnosed in 98 cases and in 37 (88%) of the 42 patients with stable AAS. CONCLUSION: The main cause of the spontaneous stabilization and occasional ankylosis of the atlantoaxial area is the development of erosions and collapse in the lateral facet joints leading to AAI.

Arthritis, Rheumatoid↗

[Evaluation of efficacy for Japanese cedar pollen-specific immunotherapy by lymphocyte proliferation test].

Peripheral mononuclear cells from 47 patients suffering from Japanese cedar pollinosis were stimulated with crude pollen extract of Cryptomeria Japonica (CJ) to evaluate the effect of CJ-specific immunotherapy. The stimulation index (SI) with crude pollen extract of CJ in the patients with excellent and good clinical outcome was significantly lower than those with poor outcome. The SI increased with the increasing symptoms in a dose dependent manner. In the patients under immunotherapy for long period, the good clinical outcome and low SI were gained. These results suggest that peripheral lymphocyte proliferation test should be a good objective indicator for allergen-specific immunotherapy.

Adult↗

Molecular cloning, sequencing, and expression of the genes encoding adenosylcobalamin-dependent diol dehydrase of Klebsiella oxytoca.

The pdd genes encoding adenosylcobalamin-dependent diol dehydrase of Klebsiella oxytoca were cloned by using a synthetic oligodeoxyribonucleotide as a hybridization probe followed by measuring the enzyme activity of each clone. Five clones of Escherichia coli exhibited diol dehydrase activity. At least one of them was shown to express diol dehydrase genes under control of their own promoter. Sequence analysis of the DNA fragments found in common in the inserts of these five clones and the flanking regions revealed four open reading frames separated by 10-18 base pairs. The sequential three open reading frames from the second to the fourth (pddA, pddB, and pddC genes) encoded polypeptides of 554, 224, and 173 amino acid residues with predicted molecular weights of 60,348 (alpha), 24,113 (beta), and 19,173 (gamma), respectively. Overexpression of these three genes in E. coli produced more than 50-fold higher level of functional apodiol dehydrase than that in K. oxytoca. The recombinant enzyme was indistinguishable from the wild-type one of K. oxytoca by the criteria of polyacrylamide gel electrophoretic and immunochemical properties. It was thus concluded that these three gene products are the subunits of functional diol dehydrase. Comparisons of the deduced amino acid sequences of the three subunits with other proteins failed to reveal any apparent homology.

Amino Acid Sequence↗

Proliferative potential of meningiomas evaluated by proliferating cell nuclear antigen expression.

Meningiomas are principally benign in nature. Some meningiomas, however, grow fast or recur even after total removal. The biological behavior of meningiomas often can not be predicted from conventional histopathological studies. A monoclonal antibody against proliferating cell nuclear antigen (PCNA) was used to investigate the usefulness of the PCNA index as a parameter to estimate the proliferative activity of meningiomas. Fifty-two meningiomas were examined. The mean PCNA index of recurrent meningiomas (3.37 +/- 0.92%) was significantly higher than that of non-recurrent meningiomas (1.12 +/- 0.51%) (p < 0.005). The PCNA indices of recurrent cases were all higher than 2.0%. A semilog linear regression analysis between tumor doubling time and PCNA index showed a significant correlation (r = 0.90, p < 0.05). An inverse linear correlation between PCNA index and interval to recurrence was observed (r = 0.62, p < 0.05). A good linear correlation was also shown between PCNA index and BUdR labeling index (r = 0.88, p < 0.01). The results of this study suggest that, providing the methods of tissue processing, immunostaining and counting of positive nuclei are unified, the PCNA index is a useful parameter for estimating the biological behavior of meningiomas.

Adult↗

Relationship between head sway and center of foot pressure sway.

We investigated the correlation between body sway and head sway in 64 healthy subjects who stood on a force-measuring platform. Each subject wore a helmet attached to a cephalograph and was asked to stand as still as possible on a platform with his feet close together for 60 sec. Subjects were asked to do this three times with their eyes closed and three times with their eyes open. We selected the test with the minimum sway for computer analysis of the sway path, sway area, ratio of anteroposterior/lateral components, sway velocity in each direction, averaged divisional frequency, and Romberg quotient. The movement of the head was significantly correlated with the center of foot pressure (COF) for the sway path, sway area, sway velocity, averaged divisional frequency, and the Romberg quotient. Our findings suggest that COF sway can be used instead of head sway to assess those five parameters.

Adolescent↗

Computed tomographic findings in peritonsillar abscess and cellulitis.

The differentiation of a peritonsillar abscess from peritonsillar cellulitis, although difficult on physical examination, is required in order to determine the appropriate treatment. Peritonsillar cellulitis can be treated with antibiotics alone, while a peritonsillar abscess should be drained. Computed tomography (CT) of the neck is often performed to identify the formation of a deep abscess in the neck, but is rarely used to diagnose peritonsillar infections. We report a patient in whom CT was a useful diagnostic tool for distinguishing peritonsillar abscess from peritonsillar cellulitis.

Adult↗

Intracellular targeting of lysosomal cathepsin D in COS cells.

Cathepsin D carries a mannose 6-phosphate sorting signal which is recognized by a specific mannose 6-phosphate receptor, presumably at the site of the trans Golgi network, which segregates cathepsin D from the secretory proteins, and results in targeting of the enzyme to the acidic prelysosomal compartments and lysosomes in mammalian cells. Recent evidence implies that another sorting signal resides within the polypeptide backbone of the precursor cathepsin D. To evaluate the role of the propeptide region of cathepsin D in mannose 6-phosphate receptor-independent targeting to lysosomes, we prepared a deletion mutant of rat cathepsin D lacking the propeptide portion and analyzed its intracellular targeting mechanism after transfection of the mutant cDNA as well as the wild-type cDNA into COS cells. The glycosylated mutant protein was retained intracellularly, and extracellular release of mutant protein was not observed after a 48 h chase. A cell fractionation experiment demonstrated that in the cells expressing the wild-type cathepsin D, the processed form of 44 kDa cathepsin D was recovered in the dense lysosomal fraction. In contrast, in the cells expressing the mutant protein, virtually all of the cell-associated cathepsin D was present in the light fraction which was enriched in the marker enzyme NADPH cytochrome c reductase, and this molecular form of cathepsin D was not observed in the dense lysosomal fraction. An immunofluorescence study revealed that the deletion mutant protein was accumulated within the endoplasmic reticulum, unlike the wild-type protein. These results suggest that the mutant cathepsin D is not correctly recognized by the intracellular sorting system in the endoplasmic reticulum, implying that the propeptide region of cathepsin D is essential for the export of cathepsin D from the endoplasmic reticulum.

Amino Acid Sequence↗