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Biomedical subjects

M Morishita

Publications and source records attributed to M Morishita.

At least 19 recordsLinked to original sources

Modification of chemo-radiosensitivity of a human lung cancer cell line by introduction of the glutathione S-transferase pi gene.

Recent studies have suggested that glutathione S-transferase pi (GST-pi) may play a role in determining tumor sensitivities to cytotoxic drugs. In order to better understand the role of this enzyme in chemo- and/or radioresistance of lung cancer cells, we examined whether introduction of GST-pi cDNA into a chemo- and radiosensitive lung cancer cell line altered its sensitivities to various chemotherapeutic agents and/or ionizing radiation, which are often used in the management of lung cancers. Modestly increased resistance of the GST-pi transfectants preferentially to sublethal damage caused by ionizing radiation as well as to adriamycin (ADM) was observed. In contrast, resistances to cisplatin (CDDP), etoposide (VP-16), irinotecan hydrochloride (CPT-11) and paclitaxel were virtually unaltered. These results suggest that GST-pi may not play a major role in chemo- and radioresistance of lung cancers, although it could afford selective and limited protection against ADM- and ionizing radiation-induced damage.

Antineoplastic Agents

[Early diagnosis of herpes simplex virus encephalitis by single photon emission computed tomography (SPECT) in patients with normal MRI].

Since treatment of herpes simplex virus encephalitis (HSVE) is most effective when started early, a sensitive and specific method for early diagnosis would be of great benefit. MRI and CT are commonly used for this purpose. In this study, we presented two patients who had serologically confirmed HSVE and had normal CT and MRI, but were diagnosed as having HSVE by means of SPECT in the early stage. Case 1 was a 56-year-old man who suddenly developed alexia. On admission, physical and neurological examination were unremarkable except for alexia, agraphia, acalculia, and left-right disorientation. Brain CT, MRI, and cerebral angiography were all normal. However, SPECT showed hyperaccumulation of 99m Tc-HM-PAO in the right temporal-occipital area. On the 5th hospital day, he became comatose. CSF study revealed marked pleocytosis. Even then, MRI including Gd-enhanced study was normal while SPECT continued to show hyperaccumulation. Detection of herpes simplex virus DNA in CSF by polymerase chain reaction was negative. Anti-HSV antibody titer in CSF and serum confirmed intrathecal production of the antibody on the 14th hospital day. Abnormal accumulation of tracer in SPECT returned to normal on the 31st day when he was alert but still had a mild Gerstman syndrome. Case 2 was a 61-year-old man with disturbance of consciousness, mental dysfunction, and generalized convulsion. He was diagnosed as having HSVE by means of CSF pleocytosis, detection of HSV DNA in CSF by polymerase chain reaction, and presence of anti-HSV antibody in the CSF. CT and MRI again revealed no abnormality while SPECT clearly showed hyperaccumulation in the left temporal lobe in an early stage. Hyperaccumulation of lipophilic tracer on SPECT study, especially in the temporal lobes, has been reported in the early stage of HSVE by previous investigators. Unlike MRI or enhanced CT, the increased tracer accumulation in SPECT does not reflect disruption of the blood-brain-barrier or inflammatory edema, but reflects hyperperfusion or some other HSVE related abnormality which is currently unknown. From these observations, we suggest that local hyperperfusion occurs before local inflammation, and that SPECT is the most useful scanning method for early diagnosis of HSVE when this disease is clinically suspected.

Encephalitis, Viral

Absorption of insulin using water-in-oil-in-water emulsion from an enteral loop in rats.

The present work was undertaken to prepare water-in-oil-in-water (W/O/W) emulsions as a carrier for insulin via the enteral route. The emulsions were prepared by a two-step procedure using a homogenizer. To avoid insulin escape from the inner aqueous phase, 3, 5, or 10% gelatin was added in the inner phase. The oily phase was composed of 5% lecithin, 20% Span 80 and 75% soybean oil. The purified water containing 3% Tween 80 was used for the outer aqueous phase. In addition, these emulsions were filtered with a membrane filter (0.45 micron) to obtain smaller emulsion particles. The stability of the emulsions was evaluated by a turbidity measurement method and photomicrographic observation. By the addition of gelatin to the inner aqueous phase and storage at 4 degrees C, the stability of the emulsions could be improved. The hypoglycemic effects of insulin after administration of emulsion to the stomach, the duodenum, the jejunum, the ileum and the colon were examined using an in situ loop method in rats. A significant hypoglycemic effect was observed at the ileum and colon loops after administration of the filtered emulsions containing 5% gelatin in the inner phase. These findings suggest that the W/O/W multiple emulsions stabilized by gelatin can improve ileal and colonic absorption of insulin.

Animals

Immunohistochemical study of gamma delta T cells in human gingival tissues.

The distribution and the density of gamma delta T cells in human gingival tissues were examined immunohistochemically in biopsy samples obtained from 20 subjects. Few gamma delta T cells were observed in gingival tissue free from inflammatory cell infiltration, but were found, albeit in low numbers, in association with inflammatory cell infiltration, especially T cells. This relationship with T cells was confirmed statistically. The ratios of gamma delta T cells to T cells in the epithelia and in the connective tissue were calculated in the sections in which more than 500 CD3-positive cells were identified. Seven of eight such epithelial specimens showed a ratio of less than 1% and one less than 2% (mean +/- SD; 0.8% +/- 0.4). In the connective tissue, 8 of 13 such specimens showed less than 1%, three less than 2%, one 3%, and one 7% (1.4% +/- 1.9). These results suggest that basically gamma delta T cells are not resident cells in the gingival epithelium such as comprise the first defense line against exogenous irritation. They may play some role in the pathogenesis of periodontal disease collaborating with alpha beta T cells in the inflammatory response.

Adult

[Serum levels of soluble receptors for tumor necrosis factor in sarcoidosis].

Tumor necrosis factor alpha (TNF-alpha) has been shown to play an important role in granulomatous diseases, including sarcoidosis. TNF-alpha starts affecting cell function by binding to specific, high-affinity receptors on the cell surface, and two types of TNF-alpha receptors have been identified. Recently, soluble forms derived these cell surface receptors (sTNF-R type I and type II) have been shown to exist and have been investigated in several diseases. The levels of sTNF-R type I and type II in serum from patients with sarcoidosis were measured, and the clinical significance of sTNF-R was evaluated. The levels of both sTNF-R type I and type II were significantly higher in serum from patients with sarcoidosis (n = 36) than in serum from control subjects (n = 15): type I, 1.93 +/- 1.28 ng/ml vs 1.31 +/- 0.40 ng/ml, p < 0.01; type II, 3.48 +/- 2.60 ng/ml vs 1.56 +/- 0.35 ng/ml, p < 0.001. The levels of these receptors were significantly higher in patients with active sarcoidosis than in those with inactive sarcoidosis: type I, 2.43 +/- 1.83 ng/ml vs 1.57 +/- 0.45 ng/ml, p < 0.05; type 4.71 +/- 2.24 ng/ml vs 2.25 +/- 0.77 ng/ml, p < 0.01. The levels of sTNF-R type I and type II correlated significantly with the level of ACE, r = 0.70, p < 0.01; and r = 0.55, p < 0.05, respectively. We conclude that measurement of the levels of both types of sTNF-R may be useful in the evaluation of disease activity in sarcoidosis.

Adolescent

[Acute disseminated encephalomyelitis (ADEM)-like exacerbation in the patients with cryptococcus meningitis treated successfully by steroid pulse therapy].

A 58-year-old man was admitted to our hospital with suspicion of aseptic meningitis. He had been well until the day before admission, when he became suffering from headache and nausea. Cerebral spinal fluid (CSF) analysis on admission revealed Cryptococcus neoformans. Neurological examination and brain CT scan showed no abnormality. On the 5th hospital day, he noticed ataxia and weakness in his right extremities and soon fell into drowsy to comatose state. CSF study revealed marked elevation of pleocytosis and oligoclonal IgG bands. The T2 weighted image of brain MRI showed multiple high intensity areas, mainly in the white matter, in cerebellar hemisphere, vermis, left medulla oblongata, left occipital lobe and parieto-occipital lobe. Steroid pulse therapy remarkably improved neurological deficit as well as MRI abnormalities. He became alert at the next day. Ataxia and motor weakness disappeared in a week. Laboratory examination before the pulse therapy revealed impairment of T cell response to mitogens and reduced number of CD8-positive cells. These abnormalities in the cell-mediated immunity were completely corrected by the steroid pulse therapy. It was hypothesized that cryptococcus infection induced the autoimmune mechanism which resulted in the ADEM-like exacerbation.

Anti-Inflammatory Agents

Effects of fluoride intake on the mineral content, acid solubility and resorption caused by experimental periodontitis of rat alveolar bone.

Adult rats were given either distilled water or drinking water containing 100 parts/10(6) of fluoride. The alveolar bone of rats given fluoride for 90 days showed an increased mineral content and decreased acid solubility compared to the bone of rats given distilled water. Experimental periodontitis was initiated in both groups after 110 days of treatment to cause alveolar bone resorption. Fourteen days later, the rats were killed and it was found that the alveolar bone resorption caused by experimental periodontitis was significantly smaller in the rats given fluoride in their drinking water than in those given distilled water. The findings suggest that fluoride intake might have a protective effect on rapidly progressing alveolar bone resorption.

Alveolar Bone Loss

Significance of interleukin 6 in patients with sarcoidosis.

Interleukin 6 (IL-6) levels in various materials from patients with sarcoidosis were determined. The subjects of the study were 38 patients with sarcoidosis and 28 healthy controls. For detection of IL-6, an enzyme-linked immunosorbent assay method was used. Interleukin 6 activity in serum was detected in 4 of 30 patients, but not in 19 controls. In bronchoalveolar lavage (BAL) fluid, following 20-fold concentration, IL-6 activity was detected in four of ten patients (nonsmokers) and three of seven controls (two of two smokers and one of five nonsmokers). Interleukin 6 levels in the supernatants of cultured monocytes and alveolar macrophages (AMs) were significantly higher (p < 0.01 and p < 0.01, respectively) in patients with sarcoidosis than in controls. Interleukin 6 production from monocytes tended to correlate with that from AMs. A significant correlation (r = 0.70, p < 0.05) was found between IL-6 production from AMs and the ratio of CD4+/CD8+ in BAL fluid, although no correlation was observed between that from monocytes and CD4+/CD8+ ratio in BAL fluid. Taken together, IL-6 may be involved in the initiation and maintenance of alveolitis by activating and causing the proliferation of T cells.

Adult

Prognosis after pacemaker implantation in cardiac sarcoidosis in Japan. Clinical evaluation of corticosteroid therapy.

Corticosteroids (CS) are useful drugs for the treatment of cardiac sarcoidosis with severe conducting defects due to sarcoid granuloma. Despite the continuous administration of CS, many patients with severe cardiac involvement may eventually die of congestive heart failure. The purpose of this study was to evaluate the efficacy of CS in patients who had a pacemaker implanted. Questionnaires were obtained from 29 institutes, and 34 cardiac sarcoidosis patients (8 males and 26 females) with pacemaker implantation were enrolled in this survey. We analyzed the survival period in these patients by the Kaplan-Meier method. There was no statistically significant difference in the survival of these patients in terms of their age, sex or disease duration (time from the onset of sarcoidosis to cardiac involvement). However, their survival was affected by the grade of dyspnea, the presence of heart failure, and certain abnormal findings on a myocardial scintigram and echocardiogram. In order to evaluate the effect of CS on the prolongation of survival, we measured the survival of the patients treated with CS and those not treated with CS. However, because of the small number of patients not treated with CS, we were unable to detect any statistically significant difference in survival. Therefore, we analyzed 104 cases in order to evaluate CS therapy: the 34 cases from the questionnaires and 70 cases reported in the literature over the last 10 years.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiomyopathies

[Clinical study of anti-phospholipid antibody in patients with sarcoidosis].

Serum antibodies against five types of phospholipids were measured by enzyme-linked immunosorbent assay (ELISA) in 55 patients with sarcoidosis. In 21 cases (38%), either IgG antibodies or IgM antibodies were detected. These antibodies were thought to mainly be infective type. This positive rate was significantly higher than that (7%) of the control group (70 cases) (p < 0.01). As to the immunoglobulin classes, 5 cases had IgG antibodies only, 11 cases had IgM antibodies only, and 5 cases had both IgG and IgM antibodies. No correlation was observed between the occurrence of anti-phospholipid antibodies (APL-Ab) and disease activity of sarcoidosis. Significant correlations were found between the occurrence of APL-Ab and skin lesions, many extrathoracic organ lesions and the persistence of abnormal chest X-ray findings for over 2 years and 5 years. From these data, it is suggested that the presence of APL-Ab is associated with prolonged disease activity of sarcoidosis.

Antibodies, Antiphospholipid

[Recent advances in immunological diagnosis for tuberculosis].

Recent advances in immunological diagnosis for tuberculosis including tuberculin Mantoux test and serodiagnosis were reviewed. New tuberculins (T1327, T1456) were reported to be more specific than the conventional one (RT23). Tuberculins from atypical mycobacteria (PPD-B, PPD-Y, PPD-F) were reported as a useful tool for the diagnosis of atypical mycobacteriosis. Optical density index method is a most appropriate method for a clinical use among several methods for the expression of antigen titer in serodiagnosis using ELISA. The duration of disease is important for understanding the results. IgM antibody rises in the early stage of the disease and comes down in 10 weeks after onset, while IgG antibody rises lately. Anti-cord factor antibody is a highly specific antibody for tuberculosis and may be a potent candidate for a clinical diagnostic tool. Anti-PPD-B antibody was elevated in atypical mycobacteriosis and pulmonary tuberculosis also. The ratio of anti-PPD-B antibody to anti-PPDs antibody was elevated in atypical mycobacteriosis while it was lowered in pulmonary tuberculosis. It may be helpful for suggesting the causative organism when the sputum smear is positive. The opposite results have been reported on the serodiagnosis in HIV infection. The usefulness of serodiagnosis for tuberculosis in HIV infected patients remained controversial.

Antibodies, Bacterial

[Levels of soluble CD4 and soluble CD8 in patients with sarcoidosis].

Levels of soluble CD4 (sCD4) and soluble CD8 (sCD8) in serum and bronchoalveolar lavage fluid (BALF) were determined in 36 patients with sarcoidosis and 20 healthy controls by an ELISA method. In addition, the possible sources of sCD4 and sCD8 were examined in detail. The sCD4 levels in serum did not differ significantly between sarcoidosis patients and controls. The sCD8 levels in the sera of sarcoidosis patients with a high serum angiotensin-converting enzyme (ACE) level were significantly higher than those of patients with a normal serum ACE level (413 +/- 148 U/ml vs. 297 +/- 76 U/ml, p < 0.01). The high ACE group also had significantly increased serum sCD8 levels as compared to controls (323 +/- 111 U/ml, p < 0.05). In the sarcoidosis patients, the mean serum sCD8 level was 308 +/- 46 U/ml in stage 0, 339 +/- 107 U/ml in stage I, 557 +/- 141 U/ml in stage II, and 474 +/- 211 U/ml in stage III. The stage II group had a significantly higher sCD8 level than either the stage 0 or I groups (p < 0.05). In the sarcoidosis patients, the sCD8 level correlated significantly with the level of either ACE or soluble Interleukin-2 receptor in serum (p < 0.05). The sCD4 level in BALF was significantly higher in sarcoidosis patients than in controls (4.10 +/- 1.90 U/ml vs. 2.39 +/- 0.12 U/ml, p < 0.01), while the sCD8 level in BALF tended to be higher in sarcoidosis patients than in controls (4.31 +/- 4.39 U/ml vs. 2.02 +/- 1.52 U/ml).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Restorative effect of short term administration of thymulin on thymus-dependent antibody production in restraint-stressed mice.

Thymulin is a well defined nonapeptide produced by thymic epithelial cells, and plays an important role in thymocyte differentiation. We investigated the restorative effect of thymulin on the stress-induced reduction in the production of antibodies against SRBC in mice. Antibody production in stressed mice was reduced to about 50% of that in normal mice. A 3-day period of administration of thymulin (1 ng/kg) restored antibody production to close to the normal level, whereas thymulin (1 ng-1 microgram/kg) did not affect antibody production in normal mice. These results indicated that thymulin normalizes the altered thymus-dependent immune responses.

Animals

The clinical course and prognosis of patients with severe, moderate or mild sarcoidosis.

During 1978-1990, 346 patients with sarcoidosis were enrolled in our institute. Of 346 patients, 295 patients were eligible for evaluation on the clinical course and prognosis. According of their clinical presentations, they were classified into 3 groups; severe, moderate and mild sarcoidosis. Of the 295 patients, 27 (9.2%) were classified as severe sarcoidosis who developed serious illness including involvement of the heart (8), lung (6), muscles (5), eyes (3), central nervous system (CNS) (3) or liver (2). The mean interval between the onset of disease to severe disability was 58.3 months. The interval was particularly long in those patients who presented with either pulmonary (100.8 months) or liver sarcoidosis (108 months). Of the 27 patients with severe sarcoidosis, 8 (29.6%) gradually became worse towards the end of their clinical course despite only mild clinical signs and symptoms at the first presentation. Therefore, the initial clinical symptoms and findings, including ocular involvement. ECG abnormalities, negative reaction to PPD, high value of serum angiotensin converting enzyme (ACE) and a small number of lymphocytes in peripheral blood, were not useful in predicting prognosis. The relationship between the maximum serum ACE value during the clinical course and the duration of the active phase was statistically significant in the 123 patients who were monitored throughout their course, suggesting that the maximum serum ACE may be a marker for assessing prognosis. Corticosteroid was administered to 76 patients (22%) with serious systemic involvement. They included 26 (96.4%) of the 27 severe sarcoidosis and 50 (37.9%) of the 132 moderate sarcoidosis. Patients with mild sarcoidosis did not receive corticosteroids.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

Site-dependent effect of aprotinin, sodium caprate, Na2EDTA and sodium glycocholate on intestinal absorption of insulin.

In order to determine an advantageous site for intestinal insulin absorption, the hypoglycemic effects of insulin after administration to the duodenum, the jejunum, the ileum and the colon were investigated using an in situ loop method. Insulin solution was administered to the various loops of fasted rats with or without aprotinin (AP) as a protease inhibitor, or absorption enhancers such as sodium caprate, Na2EDTA or sodium glycocholate. An obvious hypoglycemic effect of insulin alone was seen only in the ileum loop washed with phosphate buffered saline. When coadministered with AP, the most remarkably amplified effect was again observed in the ileum. In the ileum, the area under the serum insulin levels vs. time curve from 0 to 4 h was linearly related to the logarithm of the AP dose. Both sodium caprate and Na2EDTA significantly promoted the hypoglycemic effect of insulin at all sites, and their intensity increased towards the distal regions of the intestine. On the other hand, sodium glycocholate improved only colonic insulin efficacy. These results suggest that the ileum seems to be the most useful region in the small intestine for insulin absorption; however, insulin must be protected from proteolysis to enhance its absorption. In addition, the insulin efficacy could be increased by absorption promoters more effectively in the colon than in the small intestine.

Animals

Effects of sex hormones on production of prostaglandin E2 by human peripheral monocytes.

The effects of sex hormones on the vitro production of prostaglandin (PG) E2 by monocytes were investigated. Monocytes were obtained from heparinized peripheral blood of healthy adults and incubated for 24 hours with lipopolysaccharide (LPS) and sex hormones. After incubation, the medium was assayed for PGE2 by means of radioimmunoassay. PGE2 production by monocytes was enhanced by progesterone. Estradiol reduced PGE2 production at 0.4 ng/ml, but enhanced it at 20 ng/ml. Testosterone reduced PGE2 production. The reduced PGE2 production by monocytes treated with 0.4 ng/ml of estradiol was restored to the control level by addition of progesterone at 20 ng/ml. These results suggest that sex hormones may modulate gingival inflammation mediated by PGE2.

Adult

Sarcoidosis complicated by non-Hodgkin's lymphoma. Report of a case.

A 31-year-old male who had suffered from sarcoidosis since the age of eight developed non-Hodgkin's lymphoma 23 years after the sarcoidosis was diagnosed. During the course of chemotherapy the patient developed hepatic failure and died of pulmonary hemorrhages. This appeared to be a case of the sarcoidosis-lymphoma syndrome first described by Brincker and which has been rarely reported in Japan. We review the literature on this disorder and the immunologic abnormalities considered to participate in the lesions.

Adult