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Biomedical subjects

M Yoshihara

Publications and source records attributed to M Yoshihara.

At least 91 records · Page 5Linked to original sources

An inhibitory role of calcineurin in endocytosis of synaptic vesicles at nerve terminals of Drosophila larvae.

In this study, we tested a hypothesis that activation of calcineurin, Ca2+/calmodulin-dependent protein phosphatase 2B, is an initiating signal for synaptic vesicle endocytosis. We examined effects of calcineurin inhibitors, cyclosporin A or FK506 and calmodulin inhibitors on stimulus-induced FM1-43 uptake into nerve terminals of Drosophila larvae. Fluorescent FM1-43 labels recycling synaptic vesicles in nerve terminals. Pretreatment with cyclosporin A (5-40 microM) or with FK506 (5-10 microM) enhanced FM1-43 uptake induced by high (60 mM) K+ in a dose-dependent manner. The effect required some preincubation time of about 10 min. The nerve terminals loaded with FM1-43 were destained by electrical nerve stimulation in the cyclosporin A-pretreated preparations, confirming that FM1-43 was taken up into synaptic vesicles. Pretreatment with rapamycin (2 or 20 microM), a structural analog of FK506 which has no effect on calcineurin, or calyculin A (0.3-50 nM), an inhibitor of protein phosphatase 1 and 2A, had no detectable effect on FM1-43 uptake. On the other hand, pretreatment with trifluoperazine (1-50 microM) or with phenoxybenzamine (100 microM), inhibitors of calmodulin, enhanced FM1-43 uptake. Since endocytosis is coupled with exocytosis, it is possible that the enhancement of FM1-43 uptake results from facilitation of exocytosis. However, the frequency of spontaneous junctional potentials and the mean amplitude of evoked potentials did not change after the cyclosporin A treatment, suggesting that the exocytosis process was not significantly affected by the drug. Furthermore, we can temporally separate synaptic vesicle exocytosis and endocytosis in a Drosophila mutant, shibire (shi(ts1)). By taking advantage of this mutation, we showed that cyclosporin A and trifluoperazine enhanced synaptic vesicle recycling by directly acting on the endocytotic process. Present results are not compatible with the hypothesis, but suggest that calcineurin inhibits synaptic vesicle recycling.

Animals↗

Reduced incidence of Helicobacter pylori infection in young Japanese persons between the 1970s and the 1990s.

Although the incidence of gastric carcinoma in Japan has declined in the past several decades, there is no information about trends in helicobacter pylori infection. The purpose of the study was to clarify trends in H. pylori infection and in histologic gastritis in young Japanese subjects evaluated between 1975 and 1978 (the 1970s) versus 1991 and 1994 (the 1990s). The prevalence of H. pylori infection and the grade of gastritis in biopsy specimens were evaluated in 173 young Japanese without localized lesions in the upper gastrointestinal tract. Findings in 75 specimens obtained from subjects in the 1970s were compared with those of 98 specimens obtained from subjects in the 1990s. The prevalence of H. pylori infection in the 1970s (54.7%) was significantly higher than that in the 1990s (28.6%) (p < 0.01). The grade of inflammation and the prevalence of both mucosal atrophy and intestinal metaplasia also were significantly higher in the 1970s than in the 1990s (p < 0.01 and p < 0.05). Our data thus show a trend toward a reduced prevalence of H. pylori infection and of histologically apparent gastritis (especially atrophic gastritis). This decrease may be linked to the reported decline of gastric carcinoma in Japan.

Adolescent↗

[Two cases of tracheobronchial disruption due to blunt trauma].

Tracheobronchial disruption by blunt trauma is relative rate, but clinical course is various and sometimes fatal. A 22-year-old man (case 1) was admitted with traffic accident. Chest CT demonstrated pneumomediastinum and left pneumothorax. Bronchoscopy showed tracheal tear, but conservative therapy was selected because the peritracheal sheath remained intact. The second case was 27-year-old man, who was admitted with traffic accident. Pneumomediastinum and left tension pneumothorax were diagnosed, but bronchoscopy could not confirm the tracheobronchial disruption. As bronchial injury, lacerations and contusions of the lingular division were found in the thoracotomy, segmentectomy was carried out. When pneumomediastinum or pneumothorax is recognized in the patient of the blunt trauma, more careful examination of bronchoscopy is necessary to confirm the tracheobronchial disruption.

Adult↗

The usefulness of gastric mass screening using serum pepsinogen levels compared with photofluorography.

Chronic atrophic gastritis, which is though to be a high risk for gastric cancer, can be diagnosed by serum pepsinogen levels. We compared the usefulness of the measurement of pepsinogen levels and indirect photofluorography as indicators of gastric cancer in a mass screening involving 5,620 Japanese subjects (mean age: 60.1 years old; male : female = 2,268:3,352) in 1991 and 1992. Subjects with a serum pepsinogen I level below 30 micrograms/liter or a pepsinogen I/II ratio below 2.0 were considered to be at high risk of gastric cancer. The incidence of gastric cancer and the ratio of early cancers detected by pepsinogen levels (0.12%, 4/7) were similar to those detected by photofluorography (0.11%, 4/6). Our results showed that mass screening using pepsinogen levels was as useful as indirect photofluorography for the detection of gastric cancer in Japan. In addition, our results showed that the sensitivity of gastric mass screening was increased when the measurement of serum pepsinogen levels was combined with photofluorography.

Female↗

[A new handpiece attachment for Nd:YAG laser ablation of emphysematous bullae].

Recently, attention has been drawn to lung volume reduction for bullous emphysema by wedge excision or laser ablation. We used a neodymium: yttrium-aluminum garnet (Nd:YAG) laser with a free-beam mode to ablate peripheral emphysematous areas of lung tissue. To aid us in this procedure, we developed an attachment consisting of a stainless steel rod 3 cm in effective length, with a 1.8-cm diameter ring attached to its tip, and installed it on the tip of the laser handpiece used for free-beam laser ablation. This device has the following distinct advantages: 1) the distance between the tip of the laser and the pleura can easily be held constant, 2) the angle of irradiation can easily be maintained at 90 degrees. These result in 3) a constant area of irradiation (one square centimeter), and 4) an irradiated area that is clearly distinguished by the ring. In addition, the attachment is 5) simple and easy to construct. Three patients with bullous emphysema underwent unilateral laser ablation of the visceral pleura with the new device. All patients recovered completely. We found this rod-and-ring attachment to be useful for free-beam laser ablation.

Aged↗

Evidence that endogenous GRP in rat stomach mediates omeprazole-induced hypergastrinemia.

To investigate the physiological role of endogenous gastrin-releasing peptide (GRP) in regulating the release of gastrin, we evaluated the response of intragastric pH, gastrin, and GRP after omeprazole treatment in rats. A significant elevation of the plasma level of GRP (P < 0.01) and a significant reduction of the antral content of GRP (P < 0.05) were observed after the administration of 100 mg/kg omeprazole. The antral content of GRP was significantly decreased 12 h after omeprazole administration and thereafter gradually returned to control levels. Peak values for intragastric pH and plasma GRP were observed 3 h after omeprazole administration and before the peak of serum gastrin. The bombesin antagonist [D-Phe6]-bombesin-(6,13)-methyl ester significantly inhibited gastrin release after omeprazole treatment (P < 0.05). These observations indicate that omeprazole-induced inhibition of acid secretion stimulates the release of GRP and suggest that the secretion of GRP induced by omeprazole may stimulate the secretion of gastrin, at least in the early phase.

Animals↗

Posttraumatic ventriculomegaly: hydrocephalus or atrophy? A new approach for diagnosis using CSF dynamics.

Cerebrospinal fluid (CSF) dynamics were correlated to the changes in ventricular size during the first 3 months posttrauma in patients with severe head injury (Glasgow Coma Scale score < or = 8, 75 patients) to distinguish between atrophy and hydrocephalus as the two possible causes of posttraumatic ventriculomegaly. Using the bolus injection technique, the baseline intracranial pressure (ICP), pressure volume index, and resistance for CSF absorption (R0) provided a three-dimensional profile of CSF dynamics that was correlated with ventricular size and Glasgow Outcome Scale (GOS) score at 3, 6, and 12 months posttrauma. Patients were separated into five different groups based on changes in ventricular size, presence of atrophy, and CSF dynamics. Group 1 (normal group, 41.3%) demonstrated normal ventricular size and normal ICP. Group 2 (benign intracranial hypertension group, 14.7%) showed normal ventricular size and elevated ICP. Group 3 (atrophy group, 24%) displayed ventriculomegaly, normal ICP, and normal R0. Group 4 (normal-pressure hydrocephalus group, 9.3%) had ventriculomegaly, normal ICP, and high R0. Group 5 (high-pressure hydrocephalus group, 10.7%) showed ventriculomegaly and elevated ICP with or without high R0. The GOS score in the nonhydrocephalic groups (Groups 1, 2, and 3) was better than in the hydrocephalic groups (Groups 4 and 5). It is concluded from these results that 44% of head injury survivors may develop posttraumatic ventriculomegaly. Posttraumatic hydrocephalus, as identified by abnormal CSF dynamics, was diagnosed in 20% of survivors and their outcome was significantly worse. This study demonstrates the importance of using CSF dynamics as an aid in diagnosis of posttraumatic hydrocephalus and identifying those patients who may benefit from shunt placement.

Atrophy↗

Helicobacter pylori infection is the major risk factor for atrophic gastritis.

OBJECTIVE: To evaluate the association of both Helicobacter pylori (Hp) infection and advancing age with increased prevalence of atrophic gastritis. METHODS: Two hundred and thirty-eight subjects who had no esophagitis, peptic ulcers, or malignancies in the upper gastrointestinal tract were divided into three groups according to age: group A, < 30 yr; group B, 30-49 yr; group C, > or = 50 yr. Two biopsy specimens were obtained from the lesser curvature of the antrum and two from the anterior and posterior walls of the fundus to assess the degree of gastritis and histological evidence of Hp infection. Hp infection was evaluated by Giemsa staining and serum IgG antibodies. Serum gastrin (SG) and pepsinogen (PG) were determined by radioimmunoassay. RESULTS: In all age groups, the prevalence of atrophic gastritis was significantly more common in subjects with evidence of Hp infection. In Hp-positive subjects, the prevalence of atrophic gastritis increased with advancing age. Atrophic gastritis was extremely rare, regardless of age, in Hp-uninfected patients. SG increased, and PG I and the PG I:II ratio decreased with age in Hp-positive subjects. This trend was not apparent in Hp-negative subjects. CONCLUSION: Our results suggest that Hp infection is a stronger predictor than advancing age for atrophic gastritis.

Adult↗

[Clinical analysis on the course and prognosis of patients with Crohn's disease].

We analyzed 66 cases (47 males and 19 females) of Crohn's disease at Hiroshima University hospital from September 1975 to October 1994 to clarify the course and prognosis of Crohn's disease. The age at onset was 21.1 +/- 7.3 years old (mean +/- SD), terms between onset and diagnosis were 21.5 +/- 33.0 months (mean +/- SD) and observation period was 65.5 +/- 44.6 months (mean +/- SD). Sites of lesion were 18 ileum, 41 ileocolon and 7 colon. Thirty-one cases, 20 cases of which had intestinal obstruction, underwent surgical operation (12 ileum types, 18 ileocolic types, 1 colon type). The cumulative probability of surgery at one, five and ten years after onset of symptoms were 12.1%, 28.8% and 56.9%, respectively. As for cumulative probability of surgical operation at one, five and ten years after diagnosis were 25.8%, 36.7% and 74.4%, respectively. Results of the cumulative probability of surgery by anatomical involvement indicated that the ileum type had a statistically significantly higher risk than other types. In each analysis compliance to nutritional therapy was also an important prognostic factor. Overall, our results indicated that the site of lesion and the compliance to nutritional therapy were important factors which have an effect on the course and prognosis of Crohn's disease patients.

Adolescent↗

[Clinicopathologic evaluation on colorectal laterally spreading tumor (LST)].

Clinicopathologic characteristics of 92 colorectal laterally spreading tumors (LST) endoscopically or surgically resected were examined. Lesions were macroscopically classified into two categories according to their surface structure :(1) granular type (G type, 47 lesions), (2) flat type (F type, 45 lesions). The size (maximum diameter) of G type lesions was 24.7 +/- 11.3 mm (Mean +/- SD) and that of F type lesions was 14.2 +/- 7.4 mm. The size of G type lesions was significantly larger than that of F type lesions (p < 0.01). Among G type lesions, cancerous lesion was present in 2 (25.0%) of 8 lesions 10-14 mm in diameter, 2 (22.2%) of 9 lesions 15-19 mm in diameter and 19 (63.3%) of 30 lesions more than 20mm in diameter. Regarding F type lesions, cancerous lesion was present in 15 (46.9%) of 32 lesions 10-14 mm in diameter, 4 (80.0%) of 5 lesions 15-19 mm in diameter and 8 (100%) of 8 lesions more than 20mm in diameter. The incidence of carcinoma in F type lesions was higher than that in G type lesions irrespective of size. F type lesions with carcinoma showed a trend toward a higher frequency of submucosal invasion and F type lesions with adenoma revealed tendency of showing severe atypia in comparison with G type lesions. The adenomatous component of LST showed a tubulo-villous architecture in 13 (28.3%) of 46 G type lesions, however none of F type lesions had a tubulo-villous component. These results indicated that clinicopathologic characteristics of F type are obviously different from G type. Furthermore, F type had a higher malignant potential than G type and is thought to have a more important role as a precursor of colorectal carcinoma than G type.

Adenocarcinoma↗

Serum pepsinogen in screening for gastric cancer.

To establish a sensitive and efficient screening method for gastric cancer using serum pepsinogen, we investigated the characteristics of serum pepsinogen I and II levels and the I/II ratio and their cut-off points. We found that the pepsinogen I level and the I/II ratio were significantly lower in patients with gastric cancer than in control subjects, especially in patients with cancers of the differentiated type, the elevated type, and the depressed type without ulceration. However, sex, depth of invasion, and location of tumor did not correlate with the pepsinogen levels. A suitable cut-off point in screening for gastric cancer was a pepsinogen I level of less than 50 ng/ml and a I/II ratio of less than 3.0, as determined by receiver operator characteristics curves. The sensitivity, the specificity, and the accuracy of detection for all types of gastric cancer were approximately 55%, 75%, and 72%, respectively. If restricted to cancers of the elevated and the depressed type without ulceration, the sensitivity was approximately 85%, and the specificity and accuracy were approximately 76% and 77%, respectively. These results suggest that, in screening for gastric cancer when using pepsinogen levels and morphological examinations, the suitable cut-off point in regard to specificity is as stated above. However, regarding sensitivity, when the pepsinogen method is used alone, a pepsinogen I level of less than 70 ng/ml and a I/II ratio of less than 3.0 is acceptable.

Adenocarcinoma↗

Endoscopic treatment of submucosal invasive colorectal carcinoma with special reference to risk factors for lymph node metastasis.

A clinicopathological analysis of the risk factors for lymph node metastasis was performed in 177 patients with submucosal invasive colorectal carcinoma (CRC). The submucosal deepest invasive portion was histologically subclassified as well (W), moderately (M), or poorly (Por) differentiated. M type was further subdivided into moderately-well (Mw) and moderately-poorly (Mp) differentiated. The pattern of tumor growth was classified as polypoid growth (PG) and non-polypoid growth (NPG). Lymph node metastasis was detected in 21 (12%) of the 177 patients. Macroscopically, type IIc and IIa + IIc lesions showed a significantly higher incidence of lymph node metastasis (44% and 30%) than type IIa and I (4% and 8%). Regarding the histologic subclassification, Por and Mp lesions showed a significantly higher incidence of lymph node metastasis (67% and 37%) than W and Mw lesions (4% and 14%). NPG tumors showed a significantly higher incidence of lymph node metastasis (29%) than PG tumors (7%). The depth of submucosal invasion and lymphatic invasion (ly) were also significantly correlated with the incidence of lymph node metastasis (submucosal scanty (sm-s) invasion 4%, massive invasion 20%; ly(+) 23%, ly(-) 5%). None of the lesions with both sm-s invasion and of W or Mw type showed lymph node metastasis. These results indicate that submucosal invasive CRC with both sm-s invasion and of W or Mw type, which shows no ly, is the appropriate indication for endoscopic curative treatment.

Adenocarcinoma↗

Helicobacter pylori infection is associated with low antral somatostatin content in young adults. Implications for the pathogenesis of hypergastrinemia.

BACKGROUND: Recent studies on the role of Helicobacter pylori in the pathogenesis of duodenal ulcers have focused on the mechanism by which H. pylori infections cause exaggerated gastrin release. METHODS: We determined meal-stimulated serum gastrin concentrations and antral somatostatin content in 24 asymptomatic volunteers (6 H. pylori-infected, 18 H. pylori-uninfected). Somatostatin content was determined by radioimmunoassay in biopsy specimens obtained from the antrum. RESULTS: Fasting and integrated 2-h gastrin concentrations were significantly higher in H. pylori-positive volunteers than in H. pylori-negative volunteers (fasting, 111 +/- 16.3 pmol/l versus 53.4 +/- 3.5 pmol/l; p < 0.05; integrated 2-h, 267 +/- 41.2 pmol/l versus 70.1 +/- 2.1 pmol/l; p < 0.01). Antral somatostatin content was 0.764 +/- 0.173 ng/mg and 2.931 +/- 0.414 ng/mg in H. pylori-positive and -negative volunteers, respectively (p < 0.01). CONCLUSIONS: Low antral somatostatin content may cause hypergastrinemia in asymptomatic healthy volunteers, and H. pylori may contribute to the pathogenesis of duodenal ulcer, through this mechanism.

Adult↗

Helicobacter pylori infection, serum gastrin, and gastric acid secretion in teen-age subjects with duodenal ulcer, gastritis, or normal mucosa.

BACKGROUND: Many studies have confirmed the close association of Helicobacter pylori with duodenal ulcer (DU) in adults. However, in the subtype of DU known as 'childhood' or 'early onset DU' genetic factors seem to play a prominent role in the pathogenesis. The aim of this study was to investigate the prevalence of H. pylori in teen-age subjects with DU, gastritis, and normal mucosa and to examine the relationship of H. pylori to serum gastrin levels and gastric acid secretion. METHODS: Sixty-one teen-age subjects (24 with DU, 14 with gastritis, and 23 normal subjects) were investigated for the presence of H. pylori, antral histology, gastrin levels, basal acid output (BAO), and maximal acid output (MAO). RESULTS: All 24 patients with DU and 8 of 14 with gastritis were infected with H. pylori; none of the normal subjects were infected. Mean gastritis scores and fasting serum gastrin levels were significantly higher in patients with DU or H. pylori-positive gastritis than in subjects with H. pylori-negative gastritis or normal mucosa (p < 0.05). The difference in serum gastrin levels was also significant when patients with DU were compared with those with H. pylori-positive gastritis (p < 0.05). BAO and MAO were significantly higher in patients with DU than in subjects with H. pylori-positive gastritis or normal mucosa (p < 0.05), but there was no difference between subjects with H. pylori-positive gastritis and those with normal mucosa. CONCLUSION: H. pylori infection is associated closely with teen-age DU and gastritis and with hypergastrinemia but does not affect BAO and MAO in most infected teen-age subjects.

Adolescent↗

Cerebrovascular carbon dioxide reactivity assessed by intracranial pressure dynamics in severely head injured patients.

Appropriate management of intracranial pressure (ICP) in severely head injured patients depends in part on the cerebral vessel reactivity to PCO2; loss of CO2 reactivity has been associated with poor outcome. This study describes a new method for evaluating vascular reactivity in head-injured patients by determining the sensitivity of ICP change to alterations in PCO2. This method was combined with measurements of the pressure volume index (PVI), which allowed calculation of blood volume change necessary to alter ICP. The objective of this study was to investigate the ICP response and the blood volume change corresponding to alterations in PCO2 and to examine the correlation of responsivity and outcome as measured on the Glasgow Outcome Scale. The PVI and ICP at different end-tidal PCO2 levels produced by mild hypo- and hyperventilation were obtained in 49 patients with Glasgow Coma Scale scores of less than 8 and over a wide range of PCO2 (25 to 40 mm Hg) in eight patients. Given the assumption that the PVI remained constant during alteration of PaCO2, the estimated blood volume change per torr change of PCO2 was calculated by the following equation: BVR = PVI x delta log(ICP)/delta PCO2, where BVR = blood volume reactivity. The data in this study showed that PVI remained stable with changes in PCO2, thus validating the assumption used in the blood volume estimates. Moreover, the response of ICP to PCO2 alterations followed an exponential curve that could be described in terms of the responsivity indices to capnic stimuli. It was found that responsivity to hypocapnia was reduced by 50% compared to responsivity to hypercapnia measured within 24 hours of injury (p < 0.01). The sensitivity of ICP to estimated blood volume changes in patients with a PVI of less than 15 ml was extremely high with only 4 ml of blood required to raise ICP by 10 mm Hg. The authors conclude from these data that, following traumatic injury, the resistance vessels are in a state of persistent vasoconstriction, possibly due to vasospasm or compression. Furthermore, BVR correlates with outcome on the Glasgow Coma Scale, indicating that assessment of cerebrovascular response within the first 24 hours of injury may be of prognostic value.

Adolescent↗