Biomedical subjects

S Sakai

Publications and source records attributed to S Sakai.

At least 181 records · Page 10Linked to original sources

PubMed1997

Removal of milk by suckling acutely increases the prolactin receptor gene expression in the lactating mouse mammary gland.

To determine the effect of suckling on the prolactin receptor (PRL-R) gene expression, we measured the quantity of PRL-R mRNA in the lactating mouse mammary gland. When the pups were separated from their mother on day 5 of lactation, the long form of PRL-R (PRL-R[L]) mRNA disappeared with a half-life of 12.5 h for the first 9 h and 3.0 h for the following 9-15 h. By supplying pups to mice which had been weaned for 24 h, PRL-R(L) mRNA increased 2.5-fold during the next 6 h-period. The increase in PRL-R(L) mRNA was found in the mammary glands from which the pups removed milk. The number of mammary PRL-R protein decreased or increased following weaning or following the removal of milk by suckling, respectively. From these observations. it was concluded that the removal of milk acutely increases the level of PRL-R(L) mRNA during lactation.

Animals↗

PubMed1997

Crystal structure of a maltotetraose-forming exo-amylase from Pseudomonas stutzeri.

The three-dimensional structure of an exo-type alpha-amylase from Pseudomonas stutzeri which degrades starch from its non-reducing end to produce maltotetraose has been determined by X-ray structure analysis. The catalytic domain of this enzyme (G4-2), whose structure was determined, is a product of spontaneous limited proteolysis in culture broth. It has 429 amino acid residues and a molecular mass of 47,200, and crystallizes in ammonium sulfate solution at pH 7.5. The structure was elucidated by the multiple isomorphous replacement method and refined at 2.0 A resolution, resulting in a final R-factor of 0.178 for significant reflections with a root-mean-square deviation from ideality in bond distances of 0.013 A. The polypeptide chain of this molecule folds into three domains; the first with a (beta/alpha)8 barrel structure, the second with an excursed part from the first one, and the third with five-stranded antiparallel beta-sheets. The active cleft is formed on the C-terminal side of the beta-sheets in the (beta/alpha)8 barrel as in the known endo-type alpha-amylases. A histidine side-chain nitrogen ND1 is coordinated to one of the bound calcium ion. The recognition site of the non-reducing end of the amylose that determines exo-wise degradation is presumed to be at one end of this cleft where there is a disordered loop consisting of the 66th to 72nd residues, and a loop carrying an aspartic acid (Asp160). These structural features may be responsible for the binding of the non-reducing end of the substrate amylose.

Amino Acid Sequence↗

PubMed1997

Stomach-partitioning gastrojejunostomy for unresectable gastric carcinoma.

OBJECTIVES: To analyze the results of a new type of bypass procedure, stomach-partitioning gastrojejunostomy (SPGJ), for unresectable gastric carcinoma and to compare these results with those of conventional gastrojejunostomy (GJ). DESIGN: Retrospective review. SETTING: A university hospital in Japan. PATIENTS: Eight patients underwent SPGJ in 1 group, and 13 underwent conventional GJ in the other group. Staging was determined using preoperative diagnostic imagings and intraoperative findings. MAIN OUTCOME MEASURES: Assessment of food intake and mean survival rates. RESULTS: There were no significant differences between the 2 groups regarding male-female ratio, mean age, and histological type of carcinoma. All patients had stage IV cancers according to the classification of the Union Internationale Contre le Cancer. The rates of taking a regular meal at 2 weeks after an operation were 88% in the SPGJ group and 31% in the GJ group (P < .05). The mean 1-year survival rates for SPGJ and GJ groups were 42.9% and 7.7%, respectively (P < .05). The mean survival times were 13.4 months in the SPGJ group and 5.8 months in the GJ group (P < .05). CONCLUSIONS: Stomach-partitioning gastrojejunostomy achieved an improved quality of life and a better prognosis for patients, and it is the preferred bypass procedure for unresectable gastric carcinoma.

Aged↗

PubMed1997

Inhibitory effect of ferulic acid on macrophage inflammatory protein-2 production in a murine macrophage cell line, RAW264.7.

We investigated time-related productions of certain cytokines in lipopolysaccharide (LPS)-stimulated RAW264.7 cells, a murine macrophage cell line, by enzyme-linked immunosorbent assay. Macrophage inflammatory protein-2 (MIP-2) levels became detectable after 2 h and markedly increased over the first 8 h. Thereafter, this level remained at the same level between 10 and 16 h, and then increased again until 24 h, showing a tendency of biphasic pattern. Tumour necrosis factor (TNF)-alpha was detectable at 2 h and then increased sharply until 6 h at which it attained its peak. A low but recognizable level of interleukin (IL)-1alpha/beta was also detectable. When the inhibitory effect of ferulic acid (FA), an active component of the Rhizoma of Cimicifuga sp. used frequently as anti-inflammatory drug in Japanese Oriental medicines, was compared with that of dexamethasone (DX) on MIP-2 and TNF-alpha productions in response to LPS, both FA and DX could reduce the production of these cytokines in a dose-dependent manner. Concerning TNF-alpha, however, the inhibitory effect of FA was very weak compared with that of DX. In addition, FA as well as DX reduced MIP-2 production induced by TNF-alpha. These data suggest that MIP-2 might be induced by a direct effect of LPS and in part indirect one via initial induction of other cytokines such as TNF-alpha, leading a tendency of biphasic pattern. Comparing DX, FA is considered to be a novel and unique drug inhibiting MIP-2 production more selectively.

Animals↗

PubMed1997

Flat cancers do develop in the polyp-free large intestine.

PURPOSE AND BACKGROUND: Qualitative and quantitative analysis of many flat early cancers that have been discovered during the last decade led us to recognize that a flat route of cancer development de novo is as important a route as the polypoid one. We aim to prove through a longitudinal study that these flat early cancers indeed develop in flat mucosa and not in an adenomatous polyp. METHODS: From January 1, 1990, to July 31, 1994, 554 patients underwent at least two colonoscopies. These patients consisted of 364 males, and average age was 59 years. We searched for flat early cancers developing in polyp-free colorectal mucosa on or after a second colonoscopy. Polyp-free mucosa here means an intestinal segment proved to possess no adenomatous polyp during the preceding colonoscopies, irrespective of the presence of polyps elsewhere. RESULTS: Four flat early cancers were found developing in polyp-free colonic mucosa in four patients. Average age of the patients was 67 years. Locations of the cancers were the transverse (3) and descending colons (1). The shapes were all depressed, and average size of the lesions was 11 mm. Two lesions were endoscopically resected, and two by surgery. CONCLUSION: These four depressed cancers developing in polyp-free mucosa show that flat early colorectal cancers do arise de novo and not from an adenomatous polyp having collapsed on itself.

Adenocarcinoma↗

PubMed1997

Leiomyosarcoma originating in Meckel's diverticulum: report of a case and a review of 59 cases in the English literature.

A 49-year-old woman was referred to our hospital with complaints of epigastric colicky pain and high fever. Abdominal computed tomography and ultrasonography showed a solid tumor in the lower abdomen. Laparotomy revealed a neoplastic mass arising in Meckel's diverticulum; therefore, a segment of the ileum, including the tumor-possessing diverticulum, was resected with a lymph node dissection. A histologic examination confirmed the lesion to be leiomyosarcoma. In the English literature, 59 cases of leiomyosarcoma in Meckel's diverticulum were reported from 1941 to 1994. The majority of patients were in their 4th decade of life, with both sexes equally affected. The most frequent symptoms associated with this disease were abdominal pain with nausea, vomiting, and melena. The majority were larger than egg-size. Although Meckel's diverticulum is difficult to diagnose preoperatively, mesenteric arteriography may at times prove useful. The standard management of this particular tumor is wide segmental resection, including the tumor and diverticulum with lymph node dissection.

Female↗

PubMed1997

Acute suppurative perithyroiditis: MR findings.

We report the MR findings in two cases of acute suppurative perithyroiditis. MR has the advantages over other imaging modalities of being able to distinguish areas of inflammation from adjacent normal tissue and of allowing imaging in planes which more accurately demonstrate the extent of the lesion. MR imaging is one of the most useful methods to evaluate this entity.

Acute Disease↗

PubMed1997

Chronic expanding hematoma in the chest.

We herein report the successful surgical treatment of 2 cases of chronic expanding hematoma in the chest. The first patient, who had undergone thoracoplasty 42 years earlier due to tuberculosis, became aware of a slowly growing mass protruding in the lateral thoracic wall. The second patient, who had tuberculous pleurisy 36 years earlier, was referred to our department because of a slowly expanding intrathoracic mass revealed by a roentgenogram. The tumors, which were encapsulated chronic hematomas, were both surgically resected. These cases are rare because of the development of a very large mass after undergoing treatment for tuberculosis more than 30 years previously.

Aged↗

PubMed1997

Colour Doppler sonography of breast masses: a multiparameter analysis.

OBJECTIVE: To evaluate signals from breast lesions on both colour and spectral Doppler US, and to correlate findings with angiographic and histopathological features including microvessel density. MATERIALS AND METHODS: One hundred and sixteen breast lesions in 113 patients were evaluated with colour Doppler ultrasonography. Subjective and semi-quantitative assessment of colour signals as well as spectral Doppler analysis were performed and compared. Comparison of colour Doppler features with angiographic and histopathological findings were also carried out. RESULTS: Subjective evaluation revealed that colour signals were more commonly found in malignant (89%) than benign (56%) lesions. Malignant lesions demonstrated a more elaborate vascular network (51%) compared to 12.5% in benign lesions. Spectral Doppler analysis revealed slightly higher specificity values for the pulsatility and resistivity indices, respectively, but lower sensitivity and accuracy values compared to qualitative assessment. Colour Doppler patterns corresponded well with angiograhic images, however, the correlation between colour Doppler parameters and microvessel density was not significant. CONCLUSION: Despite the increased examination time required, spectral analysis does not appear to contribute significantly to the differentiation between malignant and benign breast tumours. Features such as the density, pattern and predominant site of colour signals may be more useful for the evaluation of breast lesions on colour Doppler imaging.

Adolescent↗

PubMed1997

Effectiveness of interferon-alpha therapy in chronic hepatitis C is associated with the amount of interferon-alpha receptor mRNA in the liver.

BACKGROUND/AIMS: This study aimed to investigate the relationship between interferon-alpha receptor mRNA in the liver and the response to interferon therapy in chronic hepatitis C. METHODS: Interferon-alpha receptor mRNA was quantified by reverse transcription polymerase chain reaction using liver biopsies from 40 patients, comprising 20 responders and 20 non-responders to subsequent interferon therapy. RESULTS: The amount of interferon-alpha receptor mRNA was significantly larger in interferon-responders (0.72+/-0.12) than non-responders (0.26+/-0.08) (p<0.01). Regardless of the response to interferon, histological activity index scores and the amount of HCV-RNA showed significant inverse correlation to the amount of interferon-alpha receptor mRNA, whereas the HCV-RNA genotype was not associated with the amount of interferon-alpha receptor mRNA. Logistic analysis and multiple regression analysis showed that the amount of interferon-alpha receptor mRNA was significantly associated with the efficacy of interferon (p=0.0275), but not with fibrosis of the liver (p= 0.2726). CONCLUSIONS: Our results suggest that the amount of interferon-alpha receptor mRNA is an important factor determining the response to interferon, and may be a new predictor of interferon response in chronic hepatitis C.

Actins↗

PubMed1997

Adjustment of creatinine clearance improves accuracy of Calvert's formula for carboplatin dosing.

Carboplatin clearance depends on the glomerular filtration rate (GFR), and Calvert's formula is frequently used to achieve a target area under the time vs concentration curve (mg ml(-1) min). Creatinine clearance is a substitute for GFR when creatinine values are determined by the Jaffé method, which is being replaced by the enzymatic method. When the enzymatic method is used, the corresponding creatinine clearance theoretically exceeds GFR, and the use of creatinine clearance as GFR in Calvert's formula results, accordingly, in overdosing of carboplatin. In this study, we have established a model for adjusting the creatinine clearance to offset this bias based on a relationship between creatinine values measured by the Jaffé method and by the enzymatic method: adjusted creatinine clearance (ml min(-1)) = creatinine clearance (ml min(-1)) x [serum creatinine (mg dl(-1))]/[serum creatinine (mg dl(-1)) + 0.2]. Subsequently, we validated this model using the data from 35 lung cancer patients. Estimated clearances of carboplatin with the original equation [creatinine clearance + 25] were systematically higher than observed clearances [mean prediction error (MPE) +/- standard error (s.e.) = 26 +/- 5%]. This positive bias was corrected by the adjustment (MPE +/- s.e. = 5 +/- 4%). When the enzymatic method is used, the adjusted creatinine clearance should be used in Calvert's formula.

Adult↗

PubMed1997

Switch from conventional to high-flux membrane reduces the risk of carpal tunnel syndrome and mortality of hemodialysis patients.

The use of a high-flux membrane, which eliminates larger molecular weight solutes with better biocompatibility, has steadily increased since the discovery of beta-2 microglobulin (beta 2m) amyloidosis in 1985. The long-term effects of a dialyzer membrane on morbidity and mortality are not completely understood. To examine the membrane effect as a factor of carpal tunnel syndrome onset and mortality, multivariate Cox regression analysis with time-dependent covariate was conducted on 819 patients from March 1968 to November 1994 at a single center. Two hundred and forty-eight of the patients were either switched from the conventional to high-flux membrane or treated only with a high-flux membrane. Fifty-one patients underwent a CTS operation and 206 died. Membrane status (on high-flux or on conventional) was considered as time-dependent covariate and risk was adjusted for age, gender, type of renal disease and calendar year of dialysis initiation. The relative risk of CTS was reduced to 0.503 (P < 0.05) and mortality 0.613 (P < 0.05) by dialysis on the high-flux membrane, compared to the conventional membrane. Serial measurements of beta 2m indicated significantly lower beta 2m to persist in patients on the high-flux membrane. The high-flux membrane decreased the risk of morbidity and mortality substantially. Larger molecule elimination was shown important not only for preventing beta 2m amyloidosis, but for prolonging survival of dialysis patients as well.

Adult↗

PubMed1997

Cloning of a cDNA for a 1-aminocyclopropane-1-carboxylate synthase that is expressed during development of female flowers at the apices of Cucumis sativus L.

In cucumber (Cucumis sativus L.) plants, it has been reported that a high correlation existed between the evolution of ethylene from the apices and the development of female flowers. We isolated three distinct cDNA encoding 1-aminocyclopropane-1-carboxylate (ACC) synthase from cucumber. Among of these, only CS-ACS2 mRNA was detected at the apices of gynoecious cucumber in which female flowers were developing. The expression of the CS-ACS2 gene was examined in the apices of three cucumber cultivars (Rensei, Ougonmegami 2-gou and Shimoshirazu) by RNA gel blot analysis. In these cultivars, both the timing and the levels of expression of the CS-ACS2 transcript were correlated with the development of female flowers at the nodes. Furthermore, the timing of the induction of expression of the CS-ACS2 gene at the apex corresponded to that of the action of ethylene in induction of the first female flower at the apex of gynoecious cucumber plants. These results suggest that the development of female flowers might be regulated by the level of CS-ACS2 mRNA at the apex.

Amino Acid Sequence↗

PubMed1997

Pharmacokinetic study of carboplatin given on a 5-day intravenous schedule.

We investigated whether carboplatin pharmacokinetics is altered when the drug is delivered daily over 5 days, compared to a single-day infusion. Carboplatin was infused in 11 patients with lung cancer, who were randomly assigned to 2 groups. In the first group, the agent was administered on a conventional single-day schedule in the first course and then on a 5-day schedule in the second course. In the second group, the order was reversed (crossover design). The dose was calculated using Calvert's formula with 24 h creatinine clearance (Ccr, ml/min) as a substitute for glomerular filtration rate (GFR): carboplatin (mg) = AUCx(Ccr+25), where AUC denotes the area under the concentration versus time curve (mg ml-1 min). No difference of carboplatin clearance between the single-day and 5-day schedule was observed (94.8 +/- 19.9 versus 96.1 +/- 29.9 ml/min, P = 0.818, paired t test). The formula systematically overestimated the carboplatin clearance: the ratio of estimated clearance/ observed clearance ranged from 1.01 to 1.58 (median 1.28; 95% confidence interval, 1.18 to 1.39). We concluded that the individual dosing strategy based on renal function can be applied with a 5-day schedule as well as a single-day schedule. Carboplatin is overdosed when Ccr is substituted for GFR in Calvert's formula.

Aged↗

PubMed1997

Effects of mitragynine on cAMP formation mediated by delta-opiate receptors in NG108-15 cells.

Mitragynine, a major constituent of the young leaves of Mitragyna speciosa KORTH., has been reported to exert antinociceptive activity in mice. To determine the mechanism the influence of mitragynine on cAMP content was measured in NG108-15 cells which possess delta opioid receptors and alpha 2B-adrenoceptors. Mitragynine inhibited the forskolin-stimulated cAMP content in a concentration dependent manner as well as morphine and noradrenaline. Mitragynine- and morphine-induced inhibition of cAMP content were blocked by naloxone. Although idazoxane inhibited noradrenaline-induced inhibition of the cAMP content, idazoxane had no effect on mitragynine-induced inhibition. These results suggest that mitragynine acts directly on opioid receptors, but not on alpha 2-adrenoceptors, to show antinociceptive activity.

Analgesics↗

PubMed1997

The regulation of the prolactin receptor gene expression in the mammary gland of early pregnant mouse.

The purpose of this research was to examine the hormonal regulation of the PRL receptor (PRL-R) gene expression in the mammary gland of early pregnant mouse. Following reverse-transcription, the quantity of PRL-R mRNA was determined by the competitive polymerase chain reaction. The level of long form PRL-R (PRL-RL) mRNA changed cyclically with the highest at estrus and the lowest at diestrus II. PRL-RL mRNA was maintained at high levels for the first 3 days of pregnancy but declined to lower levels on day 5. Mice ovariectomized on day 2 of pregnancy maintained the same level of PRL-RL mRNA during the 24 h-period. The level of PRL-R mRNA increased more than 2- and 2.7-fold with 17 beta-estradiol and PRL, respectively, and the progesterone concentration decreased its levels to 71% of the vehicle-injected control. The increasing action with 17 beta-estradiol and PRL was suppressed by administration of progesterone. Mice ovariectomized on day 3 had a 1.8-fold higher level than that of the sham-operated control. The short form of PRL-R remained at low levels throughout the experiments. The results suggested that the expression of the PRL-R gene was suppressed when serum progesterone increased during early pregnancy.

Animals↗

PubMed1997

A phase II study of carboplatin and prolonged administration of oral etoposide in patients with small-cell lung cancer.

Prolonged oral administration of etoposide may have a theoretical advantage over intravenous infusion, and carboplatin has a more favorable toxicity profile than cisplatin. A combination of carboplatin 300 mg/m2 and oral etoposide 40 mg/m2/day for 21 days was assessed in 74 (42 limited, 32 extensive disease) previously untreated patients with small-cell lung cancer. Response rate was 69% (CR 19%, PR 50%,) for limited disease and 72% (CR 9%, PR 63%) for extensive disease. Median response duration and overall survival was 6.6 and 10.1 months for limited disease, and 5.3 and 9.1 months for extensive disease, respectively. One-year and two-year survival was 36 and 10% for limited disease and 31 and 2% for extensive disease, respectively. The major toxicity was hematological with grade 4 or greater neutropenia in 36% and grade 4 thrombocytopenia in 16%, and one patient died of neutropenic fever. Non-hematologic toxicities were mild and grade 3 emesis was observed in 5% of patients. Carboplatin combined with 21-day oral etoposide showed only modest activity against small-cell lung cancer with high toxicity and did not merit further evaluation.

Administration, Oral↗

PubMed1997

Long-term feeding of high vitamin E diet improves the decreased mitogen response of rat splenic lymphocytes with aging.

This study was performed to investigate whether the long-term feeding of a high vitamin E (VE) diet has a beneficial effect on the decreased cellular immune functions caused by aging. Male Fisher rats, 12 weeks old, were fed a regular (50 mg VE/kg diet) or high VE diet (585 mg VE/kg diet) for 12 months. Then, the rats were sacrificed under anesthesia and their cellular immune functions were measured. The proliferation of splenic lymphocytes with PHA or Con A was significantly lower in old rats fed the regular diet as compared to that of young rats (two months old). In contrast, the proliferation of splenic lymphocytes in old rats fed the high VE diet was similar to that of young rats. The in vitro effect of macrophages (M phi) on the proliferation of splenic lymphocytes from young rats was investigated under Con A stimulation. Although splenic M phi isolated from old rats fed the regular diet did not have any effect on the proliferation of splenic lymphocytes, M phi from old rats fed the high VE diet significantly enhanced the proliferation of splenic lymphocytes. The responsiveness of splenic lymphocytes isolated from each group to the M phi of young rats under Con A stimulation was not significantly different between the young rats and old rats fed the regular diet. In old rats fed the high VE diet, the responsiveness of splenic lymphocytes to young rat M phi was significantly higher than that of the young rats or old rats fed the regular diet. Furthermore, the high VE diet induced a significant increase in interleukin 2 (IL2) production from splenocytes in both young rats and old rats following in vitro stimulation with Con A for 48 h. These results suggest that VE has the ability to improve the decreased cellular immune functions caused by aging, and appears to be associated with the enhancement of both M phi functions and lymphocyte responsiveness.

Aging↗