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Biomedical subjects

K Kashima

Publications and source records attributed to K Kashima.

At least 235 records · Page 13Linked to original sources

Effect of a somatostatin analogue (SMS 201-995) on hemodynamics and glucagon secretion in cirrhotic rats.

The effects of somatostatin analogue, SMS 201-995, on systemic and splanchnic hemodynamics and glucagon secretion were investigated in control and cirrhotic rats induced by thioacetamide administration. Hemodynamics were measured using the radioactive microsphere method. Immunoreactive glucagon (IRG) was determined in the portal vein and femoral artery and the splanchnic output (OP) of IRG was calculated. In control rats, SMS 201-995 induced a decrease of 5.6% in portal venous inflow and a 25.8% decrease in OP of IRG. In cirrhotic rats, SMS 201-995 produced a 14% decrease in portal pressure, a 13.6% decrease in portal venous inflow, and a 57.8% decrease in OP of IRG. In systemic hemodynamics no significant changes were noted following SMS 201-995 administration in the control or cirrhotic rats. The ratio of cirrhotic rats to the controls in the rate of decrease in portal venous inflow was similar to that in the percentage of decrease in OP of IRG. We conclude that SMS 201-995 is useful for the treatment of portal hypertension because of its effect of reducing portal pressure with mild changes in systemic hemodynamics. We suspect that the decrease in portal venous inflow by SMS 201-995 is mainly due to a reduction in the release of glucagon, a vasodilatory gastrointestinal hormone.

Animals↗

Hypertonic glucose inhibits the production of oxygen-derived free radicals by rat neutrophils.

We studied the influence of graded degrees of hypertonic glucose or sucrose on the generation of oxygen-derived free radicals by rat neutrophils. Hypertonic glucose and sucrose exerted dose- and time-dependent inhibition of chemiluminescence amplified by luciferin analog (CLA-DCL) and luminol (L-DCL) in response to fMLP. Hypertonic glucose was more effective to this chemiluminescence inhibition than hypertonic sucrose was. This inhibition of hypertonicity was more effective in CLA-DCL than in L-DCL. Although the production of superoxide anion measured by the reduction of ferricytochrome c was more inhibited by hypertonic glucose than by hypertonic sucrose, the myeloperoxidase activity was not affected by either glucose or sucrose hyperosmolarity. These data suggest that hyperosmotic state by itself and an additional direct glucose-toxicity may contribute to the impaired neutrophil function in the diabetic state.

Animals↗

Effects of bile acids and taurine on the lipid fluidity of hepatic microsomes in normal and bile duct-ligated rats--a spin label study.

In cholestasis and obstructive jaundice, hepatic bile acids and taurine content increase significantly and bile acids change in compositions. For example, increases in cholic acid, beta-muricholic acid and taurine-conjugated bile acids occur in rats. In this study, to clarify the significance of changes in bile acid composition in obstructive jaundice, the effects of various bile acids and taurine on the fluidity of the hepatic microsomal membrane were studied by the electron spin resonance spin-label method in normal and bile duct-ligated (for 10 days) rats. The flow properties (order parameter) of the shallow and deep layers of the membrane were determined with 5- and 12-doxyl stearic acid, respectively. Bile acids mainly affected the fluidity of the shallow membrane layer. The fluidity of the hepatic microsomal membrane was decreased in bile duct-ligated rats. Conjugated cholic acid (taurine-conjugated cholic acid, glycine-conjugated cholic acid and non-conjugated beta-muricholic acid exerted effects that increased fluidity in comparison with non-conjugated cholic acid and chenodeoxycholic acid, a precursor of beta-muricholic acid. Taurine had no clear effect on fluidity. In conclusion, cholic acid conjugation and beta-muricholic acid formation may be mechanisms which protect against the decrease in lipid fluidity of hepatic biomembranes in cholestasis or obstructive jaundice. Taurine may also affect fluidity through the formation of taurine-conjugated bile acids.

Animals↗

Biotin-containing intranuclear inclusions in endometrial glands during gestation and puerperium.

Intranuclear inclusions sometimes are observed in endometrial glands, especially during puerperium, and superficially they resemble those from herpesvirus-infected cells. To study the significance of the inclusions, endometrial and placental tissue from 215 subjects, including 69 pregnancy-associated samples, were examined. With screening by peroxidase-labeled avidin alone, followed by the peroxidase reaction, only pregnancy-related endometrium (in 32 cases) demonstrated reactivity in the intranuclear inclusions. These intranuclear inclusions demonstrated positive immunostaining for biotin using the peroxidase-antiperoxidase method in all but six cases, whereas there was no reaction for Herpes simplex in any of the cases. The endometrial tissues of the 32 cases were obtained from the 16th gestational week to the 37th postpartum day. Although the histogenesis of these intranuclear inclusions has not been clarified, they should not be mistaken for those in endometrial cells infected by herpesvirus because of intranuclear biotin and a false-positive histochemical reaction in the avidin-biotin-peroxidase complex method.

Biotin↗

Establishment and immunohistochemical characterization of an experimentally induced transplantable malignant schwannoma in the rat and two derived cell lines.

Oral administration of N-methyl-N'-nitro-N-nitrosoguanidine induced gastrointestinal tumors in 15 out of 19 rats: six adenomas, seven adenocarcinomas, one fibrosarcoma and one malignant schwannoma that was homotransplantable. Both the original and transplantable tumor exhibited characteristic morphological features and immunoreactivity identical to that of a human malignant schwannoma: positive reaction for S-100 protein, neuron specific enolase, glial fibrillary acidic protein, myelin basic protein and vimentin. In addition, alpha-smooth muscle actin was expressed in both tumors. Cultured tumor cells derived from the transplantable tumor at passage 3 produced 18 clones which showed anchorage independent growth in soft agar. From these clones, two cell lines showing characteristic immunoreactivity, designated as RMS-1 and 2, were established. In general, the immunoreactivities of the two cell lines were similar to those of the original tumor; however, the RMS-1 cell line demonstrated positive immunoreaction for neurofilaments and RMS-2 was negative for alpha-smooth muscle actin. Subcutaneous, injection of cultured cells from both cell lines into athymic BALB/c nude mice induced tumors identical to the original tumor. In the present study, transplantable malignant schwannoma was established in the rat and two phenotypes were isolated and established as cell lines.

Administration, Oral↗

Identification of basic fibroblast growth factor in papillary carcinoma of the thyroid.

Basic fibroblast growth factor (bFGF) was identified in the papillary carcinoma of the human thyroid. Immunohistochemically, it was found that the reactivity for bFGF was localized in the cytoplasm of the neoplastic cells of the five papillary carcinomas. However the extract of the papillary carcinomas contained the mitogenic activity for endothelial cells. This bioactive molecule was determined as bFGF by using the heparin-Sepharose affinity chromatography and western blot analysis. The bFGF derived from human thyroid papillary carcinoma and the recombinant human bFGF stimulated the bromodeoxyuridine incorporation by the cultured human thyroid papillary carcinoma cells. These cells also showed positive staining for thyroglobulin and cytokeratin. These results indicate that bFGF, probably produced by the neoplastic cells, plays an important role in the development of papillary carcinoma of the thyroid with stimulation of angiogenesis as well as proliferation of the parenchymal cells.

Carcinoma, Papillary↗

Membrane lipid fluidity affects the nitroxide radical decay of 5-doxyl stearic acids in isolated rat hepatocytes.

We investigated the effect of membrane fluidity on the nitroxide radical decay rate of 5-doxyl stearic acid in spin-labeled rat hepatocytes. The half-time (t1/2) for the EPR signal decay of 5-doxyl stearic acids incorporated into the membranes of isolated rat hepatocytes was 12 min (mean value). When spin-labeled hepatocytes were separated into membrane and cytosol fractions, the t1/2 of the membrane fraction was prolonged by more than 2 hrs. However, when the cytosolic fraction was added to the membrane fraction, the radical decay reaction recovered (t1/2 was 27 min). Incubation of hepatocytes with a stream of 95% O2 at 37 degrees C for 2 hrs prolonged t1/2 by 106% and was associated with a 18% decrease in water-soluble antioxidant content. When the measurement temperature was changed from 24 degrees C to 37 degrees C, t1/2 was shortened with a decrease in the order parameter (S). The t1/2 and S in hepatocytes treated with phosphatidylcholine (PC) were reduced by 14% and 0.008, respectively. Conversely, after treatment with phosphatidylethanolamine (PE), PC+cholesterol and PE+cholesterol, t1/2 and S increased by 14% and 0.014, 20% and 0.018 and 29% and 0.040, respectively. These findings suggest that the nitroxide radical decay of 5-doxyl stearic acids incorporated into hepatocyte membranes is mediated by the antioxidants in the cytosol fraction, and that the nitroxide radical decay rate is affected not only by water-soluble antioxidant content but also by the membrane lipid fluidity of the hepatocytes.

Animals↗

[Localization of salazopyrin in colonic mucosa patients with ulcerative colitis].

In this study SASP metabolite levels were measured in colonic mucosal specimens and plasma samples from 31 patients with ulcerative colitis (UC) under treatment with the drug. Colonic tissue specimens were obtained by endoscopically guided biopsy and plasma was isolated from peripheral blood. Measurements were performed by HPLC according to the procedure of Fischer et al. The levels of 5-ASA and SP in either of colonic tissue or plasma were significantly lower than those of Ac-5-ASA and Ac-SP, respectively. The tissue level of 5-ASA had a significant correlation to the dosage of 5-ASA. The tissue levels of 5-ASA and Ac-5-ASA were low in an active stage of UC than during a remission period and the difference observed with respect to the latter metabolite was significant. These findings suggest that acetylation of 5-ASA is inhibited in the colonic mucosa in an active stage of the disease.

Adult↗

[Usefulness of serum pancreatic phospholipase A2 determination in patients with various pancreatic diseases].

A radioimmunoassay kit (SHIONORIA P-PLA2) to measure human serum pancreatic phospholipase A2 (P-PLA2) concentrations was evaluated for their basic properties and clinical usefulness. The performance of the kit was found to be quite satisfactory. To test its clinical usefulness, specimens mainly from patients with pancreatic diseases were obtained and examined for serum P-PLA2 levels. All serum specimens from patients with acute pancreatitis (n = 7) were found to have elevated levels of serum P-PLA2. In patients with chronic pancreatitis (n = 93) and pancreatic cancer (n = 37), serum P-PLA2 levels showed a wide range of distribution, from abnormally elevated values to abnormally low values. We compared these data with those of other pancreatic markers such as: amylase, elastase 1, trypsin, and PSTI. Among these, P-PLA2 was highly specific to pancreatic disease and best represented the state of pancreatic disorders. Abnormally elevated levels of serum P-PLA2 concentrations seem to reflect the inflammation of pancreas, while abnormally low levels indicate the hypofunction of pancreatic exocrine glands. These results suggest that the measurement of serum P-PLA2 concentrations is a useful diagnostic test for pancreatic disorders.

Clinical Enzyme Tests↗

[Efficacy of fluconazole on systemic mycosis associated with hematologic malignancies and a study on diagnostic value of plasma beta-D-glucan levels].

Efficacy of fluconazole (FLCZ), an anti-fungal agent of triazole derivatives, was evaluated in patients with systemic mycoses and suspected mycoses associated with hematologic malignancies including leukemia, myelodysplastic syndrome and malignant lymphoma. Plasma beta-D-glycan levels, the differences between the levels determined toxicolor test and in endospecy test, were also investigated. Fourteen patients with systemic mycoses and 31 patients with suspected mycotic infections were treated with intravenous administration of FLCZ at a daily dose of 400 mg. Excellent to good responses were observed in 4 of the 14 patients (28.6%) with definitive diagnosis of mycosis, and in 18 of the 31 patients (58.1%) with suspected fungal infections, with an overall efficacy rate of 48.9% (22/45). Levels of plasma beta-D-glycan correlated well with efficacies of FLCZ in 19 of 30 patients. In several cases, however, plasma beta-D-glucan levels were low during the entire course of treatment. Even in 10 cases of definite mycosis, 4 cases showed low levels of plasma beta-D-glucan (below 15 pg/ml by repeated determinations). The results indicate that FLCZ is an effective agent for the treatment of severe systemic fungal infections in patients with hematologic disorders. Deep seated mycosis cannot be ruled out even when its plasma levels of beta-D-glucan are low.

Adolescent↗

[Cell proliferation and maturation of ectopic submucosal glands of the stomach].

Stomachs with multiple submucosal glands keep our attention because of their high risk for having gastric carcinomas, but little is known about the relationship between submucosal glands and occurring cancers. So we investigated the structure of submucosal glands including location of proliferating cells. We labeled proliferating cells of three stomachs with cancerous lesions by circulating artificial blood through the isolated organs with bromodeoxyuridine (BrdU). Serial sections of submucosal glands were stained with hematoxylin eosin, periodic acid Schiff, Alcian blue, high iron diamine-Alcian blue, concanavalin A paradox, galactose oxidase Schiff as well as anti-BrdU immunohistochemically. Results showed that most of submucosal glands were composed of functionally matured cells and these cells made regular structure just like those of mucosal layer. Labeling index of BrdU of these submucosal glands were low (0.2%-0.7%). Two atypical glands were seen, and labeling index were 2.6% and 22.2% respectively. In conclusion, submucosal glands of the stomachs were thought to be made by moving proliferating cells from mucosal layer to submucosal layer. So we saw these submucosal glands paracancerous lesions rather than precancerous ones. But we couldn't deny the possibility to occur cancerous lesions from atypical glands in submucosal glands.

Aged↗

[Clinical evaluation of imipenem/cilastatin sodium and fosfomycin as second-line combination chemotherapy in severe infections associated with hematologic disorders].

Imipenem/cilastatin sodium (IPM/CS) which is a broad-spectrum agent against both Gram-positive and -negative bacteria was used in combination with fosfomycin (FOM) as a second-line chemotherapy for severe infections associated with hematologic disorders. FOM was partnered with IPM because FOM may enhance the bacteriocidal effects of IPM when given as pretreatment to IPM/CS therapy. Fifty two patients were treated with IPM/CS plus FOM. Of them, 41 were evaluated for effectiveness. Eleven patients were not evaluated: 4 were treated with a combination of other regimens such as cefixime, gamma-globulin, G-CSF and a large dose of methyl prednisolone; 2 were given IPM/CS plus FOM as a first choice; 3 were observed to have gastrointestinal side effects such as nausea which led to the discontinuation of the combination therapy; and 2 were thought to be suffering from not infectious but tumor fever. An excellent response was observed in 15 (36.6%) patients and a good response in 10 (24.4%), for a overall efficacy rate of 61.0%. Efficacies was 71.4% (5/7) in patients with sepsis, and 60.0% (9/15) in patients whose peripheral granulocyte count was below 100/microliters before chemotherapy. The elimination rates of Gram-positive and -negative bacteria were 57.1% (4/7) and 75.0% (6/8), respectively. In particular, 75.0% (3/4) of Pseudomonas aeruginosa identified were eliminated. Two patients who suffered from tumor fever, 2 who did not receive chemotherapy before the combination chemotherapy and 3 who did not receive a full course of the combination chemotherapy because of side effects, were included in the final evaluation of safety. Side effects were observed in 18 of 48 patients (37.5%). In 1 patient, skin eruption occurred 3 days after the initiation of the combination chemotherapy. In 17 patients, gastrointestinal symptoms such as nausea and vomiting were identified after a few days of IPM/CS plus FOM administration. Degree's of the symptoms were mild, however. Therefore, the treatment was not withdrawn. No abnormal laboratory results such as eosinophilia, liver disfunction or renal disfunction were observed. These results show that IPM/CS plus FOM is effective as a second-line combination chemotherapy for the treatment of severe infections in patients with hematologic disorders.

Adolescent↗

Aging studies on normal lens using the Scheimpflug slit-lamp camera.

PURPOSE: To study the changes in density and thickness in normal lenses related to aging, and to study changes in anterior chamber depth related to aging. METHODS: Eighty nine normal volunteers (ages 9-80 yr) were examined and their eyes were photographed to obtain Scheimpflug photographs. The images were digitized and linear densitometry was performed, dividing the lens into five areas: posterior capsular (area 1), posterior cortical (area 2), nuclear (area 3), anterior cortical (area 4), and anterior capsular (area 5). Total lens thickness and anterior chamber depth were similarly measured for 90 normal eyes from the densitometry profiles. These were correlated with age. RESULTS: There was a strong positive correlation between increasing age and the density in all lens areas (area 2: r = 0.805; P < 0.0001; area 3: r = 0.836, P < 0.0001; area 4: r = 0.767, P < 0.0001; and area 5: r = 0.319, P < 0.0023), except the posterior capsular area, where correlation was negative (area 1: r = -0.426; P < 0.0001). In addition, there was a significant correlation between age and overall lens thickness (r = 0.756; P < 0.0001), thickness of nucleus (r = 0.543; P < 0.0001), and cortex (r = 0.632; P < 0.0001), and a negative correlation with anterior chamber depth (r = -0.513, P < 0.0001). CONCLUSION: This report shows human lens changes in density and thickness correlated with aging using Scheimpflug photography and image analysis techniques. The results will aid future development of systems for automated detection, classification, and monitoring of human cataracts, as well as other anterior segment disorders.

Adolescent↗

[Analysis of proliferative activity in gastric biopsy specimens by combined BrdU and DNA polymerase alpha immunohistochemistry].

To evaluate correctly the proliferative activity of tumor cells, it is necessary to clarify not only S-phase fraction but also the growth fraction of tumor tissues. We used combined BrdU and DNA polymerase alpha (pol-alpha) immunohistochemistry to gastric biopsy specimens, and analyzed the proliferation of the neoplastic lesions of various degrees of malignancy. The results were as follows: The distribution of pol-alpha positive cells were almost the same as that of BrdU positive cells, but the percentage of pol-alpha positive cells was higher than that of BrdU positive cells irrespective of the mucosal specimens. In the adenomas, both BrdU and pol-alpha positive cells distributed generally superficially in the mucosal layer. In the well differentiated adenocarcinomas, both BrdU and pol-alpha positive cells distributed diffusely in the deeper layer of the mucosa. The ratio of the number of BrdU positive cells to that of pol-alpha positive cells, which means the S-phase fraction in the growth fraction, was higher in the tumor and that higher in the well differentiated adenocarcinomas than that of the adenomas. In conclusion, the combined BrdU and pol-alpha immunohistochemistry in gastric biopsy specimens are useful to evaluate the degree of malignancy.

Adenocarcinoma↗

[Disease-free survival in a patient with squamous cell lung carcinoma following complete response with the combination chemotherapy of cisplatin and etoposide].

Disease-free survival is reported in a patient with non-small cell lung carcinoma successfully treated with the combination chemotherapy of cisplatin and etoposide (CDDP-ETOP). An 80-year-old woman was diagnosed as having squamous cell carcinoma of the lung with bone metastasis. Chest X-ray showed a tumor (64 x 68 mm in size) in the S1/4 segment of the right lobe, and CT scan revealed no apparent metastasis of hilar lymphnode. In March 1989, the patient achieved a complete response (CR) after two courses of CDDP-ETOP therapy, followed by ETOP(100mg) every two weeks and daily UFT (400 mg) for 10 months. Subsequently, a single course of CDDP-ETOP was administered as a consolidation therapy. The patient is alive with no evidence of recurrent disease for 3 years and half after achieving CR.

Aged↗