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Biomedical subjects

T Nose

Publications and source records attributed to T Nose.

At least 19 recordsLinked to original sources

Difference between cancer cells and the corresponding normal tissue in view of stereoselective hydrolysis of synthetic esters.

This study has aimed at taking information necessary for design of anticancer prodrugs modified with chiral acyl group, especially about the effect of chirality of the acyl group on its enzymic removal in specific cells. Thus, 13 species of chiral esters were synthesized and stereoselectivity in their enzymic hydrolysis was investigated with six cancer cell lines, solid tumors, and the corresponding normal tissues. Cultured cancer cells from rat liver, pancreas, and muscle hydrolyzed the R enantiomer of (+/-)-ethyl 2-methoxy-2-phenylacetate (3c) more preferentially than its antipode, whereas this stereoselectivity was reversed in the reaction by homogenate of the corresponding normal tissue of rat. The difference in stereoselectivity between cancer cells and normal tissue was also found in the hydrolysis of other esters including those of actual anticancer agents, p-hydroxyaniline mustard and 5-fluorouridine. The investigation was expanded to real tumor to show that the degree of stereoselectivity or the hydrolytic activity was significantly different between a human brain tumor and its surrounding normal tissue for such substrates as (+/-)-ethyl 2-phenoxypropanoate and N-trifluoroacetylphenylalaninate. The esterases of rat liver cancer cells (Anr4) and normal rat liver gave different band patterns in active staining after gel electrophoresis. The enzymes were fractionated by ion exchange column chromatography and then tested on their stereoselectivity against (+/-)-3c. Comparison of the results and electrophoretograms of the fractions suggests that esterases with different stereoselectivity are expressed in different ways by normal and cancer cells. These results show that stereoselectivity in enzymic hydrolysis of some synthetic chiral esters is different between cancer and normal cells, leading to the possibility that specific activation of ester-type anticancer prodrugs in cancer cells would be controlled by the chiral structure of the acyl group.

Animals

Cyclooxygenase inhibitors augment the production of pro-matrix metalloproteinase 9 (progelatinase B) in rabbit articular chondrocytes.

Matrix metalloproteinase 9 (MMP-9/gelatinase B) has recently been proposed to participate in the destruction of articular cartilage. Here, we report that interleukin 1 (IL-1) enhances the production of the precursor of MMP-9 in rabbit articular chondrocytes in primary culture, and this IL-1-mediated production of proMMP-9 is greatly augmented by cyclooxygenase inhibitors such as diclofenac and indomethacin, whereas the constitutive production of proMMP-2 (progelatinase A) is not modulated by IL-1 and/or cyclooxygenase inhibitors. Exogenous prostaglandin (PG) E1 and PGE2 suppress the proMMP-9 production in a dose-dependent manner. Similar results are also obtained with cultured rabbit synoviocytes. These results provide the first evidence that PGE down-regulates the production of proMMP-9 in chondrocytes and synoviocytes. Thus, cyclooxygenase inhibitors probably exert undesirable catabolic actions on the maintenance of articular cartilage under inflammatory conditions.

Alprostadil

Leukoencephalopathy associated with intra-arterial ACNU in patients with gliomas.

Thirty cases of gliomas treated by surgery, radiotherapy and intra-arterial (IA) ACNU were reviewed with a focus on the late side-effect known as leukoencephalopathy. All cases were classified into three groups; remission (10 cases), regrowth (15 cases) and leukoencephalopathy (5 cases) from their outcome. The average total doses of IA ACNU were 49.8 mg/sqm body surface area in the remission group, 157.3 mg/sqm in the regrowth group and 203.1 mg/sqm in the leukoencephalopathy group. There were significant differences in the total IA ACNU doses between the remission group and both regrowth and leukoencephalopathy groups, while no significant differences were noticed in the dose of radiation given. There was a correlation between the total dose of IA ACNU and the occurrence of leukoencephalopathy. An autopsy of a typical case of leukoencephalopathy revealed various degrees of myelin breakdown and thickening of arterial walls, which probably manifested progressive dementia accompanied by urinary incontinence and gait disturbance.

Adolescent

Systemic lupus erythematosus: a case-control epidemiologic study in Japan.

BACKGROUND: Systemic lupus erythematosus (SLE) is designated by the Japanese government as one of the intractable diseases and all patients, who suffer from these diseases, are registered to get financial aid for treatment. Using newly registered SLE patients, a case-control study was conducted to evaluate potential risk factors. METHODS: Two-hundred and eighty-two women SLE patients, newly registered to receive financial aid for treatment, and 292 randomly selected health examination participants at public health centers (controls) were surveyed from April 1988 through March 1990. By means of a self-administered questionnaire, data concerning demographic variables, smoking and drinking habits, past medical and reproductive history, and family history were collected. RESULTS: Based on unconditional logistic regression analysis, the risk of SLE was significantly increased for current smokers (age-adjusted odds ratio (OR) = 2.31, 95% confidence interval (CI) 1.34-3.97). Alcohol and milk intake were inversely associated with risk. Family histories of asthma and collagen diseases, including SLE, were associated with significantly elevated risk of SLE (OR = 2.07, 95% CI 1.14-3.77; OR = 5.20, 95% CI 1.08-24.95, respectively). Regarding reproductive function, women with menarche at age 15 or later had significantly higher risk than those, who started menstruating before age 12 (OR = 3.82, 95% CI 1.66-8.81 for menarche at > 15 years and OR = 2.90, 95% CI 1.14-7.39 for menarche at > or = 16y). CONCLUSIONS: Our study suggests several risk factors, including smoking, family history, and reproductive history that may increase the risk of SLE.

Adolescent

Osteomas of the skull: comparison of magnetic resonance imaging and histological findings.

Magnetic resonance (MR) images of five patients with osteomas of the skull and six patients with other primary skull tumors were reviewed. All osteomas appeared as low-intensity areas on T1-weighted images. T2-weighted images showed homogeneous low-intensity areas in two dense osteomas, a high-intensity area in one spongy osteoma, and mixed intensity areas in two mixed spongy and dense osteomas, respectively. The signal intensities of osteomas on T2-weighted MR images correlated well with the histological findings. Other skull tumors showed no specific MR imaging appearance.

Adolescent

Effect of lymphokine-activated killer cells with or without radiation therapy against malignant brain tumors.

The use of autologous lymphokine-activated killer (LAK) cells to treat malignant brain tumors was evaluated in 10 patients, one with metastatic malignant melanoma and nine with malignant glioma. LAK cells were obtained by culturing autologous peripheral blood lymphocytes with human recombinant interleukin-2 (rIL-2) for 7-28 days. All patients underwent surgery to remove as much tumor as possible and an Ommaya reservoir was implaced in the tumor cavity. Two of the 10 patients had received radiotherapy elsewhere, so were treated with LAK cells alone. Eight patients were treated with a combination of LAK cells and radiotherapy, using 1.8-2.0 Gy fractions given five times a week with a total dosage between 54 and 65 Gy. LAK cells and rIL-2 were injected to the tumor cavity via the Ommaya reservoir once a week for inpatients and once a month for outpatients. The duration of the LAK therapy ranged from 3 to 23 months (mean 13.7 mos). Neuroimaging evaluation revealed two complete responses, three partial responses, four no changes, and one progressive disease. In one patient with pontine glioma, the Karnofsky performance score was raised from 20 to 60. There were no side effects after the injection of LAK cells and rIL-2. The results suggest low-dose LAK therapy is a useful and safe treatment modality for malignant brain tumors.

Adult

Intrasyringal hemorrhage of the cervical cord associated with Chiari type I malformation--case report.

A 34-year-old male presented with intrasyringal hemorrhage associated with Chiari type I malformation manifesting as a history of repetitive severe pain around his neck and back and progressive sensory disturbance. Magnetic resonance imaging clearly demonstrated syringomyelia at the cervical region associated with Chiari type I malformation and hemorrhage in the syrinx which was strongly suggestive of bleeding into pre-existing syringomyelia or Gowers' syringal hemorrhage. Irrigation of the syrinx and syringosubarachnoid shunting were performed, but rebleeding occurred causing shunt malfunction. Shunt revision was performed, but a new cavity developed above the original syrinx. Foramen magnum decompression resulted in successful reduction of the new syrinx and subsequent neurological improvement. Simultaneous foramen magnum decompression and syrinx irrigation may be a better approach to treat this disease.

Adult

Cerebral gumma mimicking glioblastoma on magnetic resonance images--case report.

A 39-year-old female presented with a syphilitic cerebral gumma mimicking small glioblastoma multiforme manifesting as visual impairment. Magnetic resonance imaging showed a low signal intensity area on T1-weighted images and marked small ring-like enhancement less than 1 cm in diameter following the administration of gadolinium. The symptoms and radiological abnormalities improved several weeks after penicillin therapy. The small ring-like enhancement was probably caused by inflammation associated with treponemal infection. A mass with a small ring-like enhancement less than 1 cm in diameter is a useful finding indicating an inflammatory lesion rather than a glial tumor.

Adult

Clinical application of diffusion-weighted magnetic resonance imaging to intracranial disorders.

Diffusion-weighted magnetic resonance imaging was performed to determine the changes in water diffusion and to investigate the detectability of diffusion anisotropy in patients with intracranial disorders. Diffusion maps of the apparent diffusion coefficient (ADC) were created of 19 patients with cerebral infarction, five with intracerebral hematoma, four with glioma, four with meningioma, four with hydrocephalus, and five with subdural hematoma. ADC was increased in chronic cerebral infarction and glioma, and decreased in acute cerebral infarction, meningioma, and the marginal area of glioma compared with the ADC of the normal gray matter. There was a significant difference in ADC between the marginal and internal areas of glioma. Increased ADC may be due to increased vasogenic edema in infarction and a lack of significant restriction of diffusion within glioma. Decreased ADC can be attributed to restricted diffusion caused by cytotoxic edema in infarction and the underlying histological pattern of densely packed tumor cells in glioma. Diffusion anisotropy of the internal capsule was less detectable in pathological than normal hemispheres. Diffusion anisotropy was less detectable in patients with hydrocephalus and subdural hematoma. Intracranial lesions were thought to have influenced the compression of the brain structures and cells, resulting in decreased diffusion. The measurement of ADC by diffusion-weighted magnetic resonance imaging has the potential for greater understanding of the biophysical changes in various intracranial disorders, including correct diagnosis of cerebral infraction, and histological diagnosis of brain tumor.

Adolescent

[Transient cerebellar mutism after removal of a posterior fossa tumor in two cases].

We have reported the cases of two young patients who presented transient mutism in the course of recovery from removal of a cerebellar medulloblastoma. Although cerebellar symptoms were observed immediately after surgery, neither consciousness disturbance nor sensory aphasia was observed when the patients were mutic. From the analysis of serial magnetic resonance imaging (MRI). Gd-enhanced regions were noticed in the dentate nucleus and the cerebellar peduncle when mutism appeared, and they disappeared when mutism was gone. Although the mechanism of this interesting symptom is not clear, these MRI findings may indicate that focal ischemia or edema associated with surgical procedure may play a role in the appearance of this symptom.

Adolescent

[Low incidence of point mutation of N-ras oncogene in human gliomas].

We examined the incidence of point mutations in codon 12 and 61 of N-ras gene in human gliomas using PCR with mismatched primers. This method detects point mutations. PCR with mismatched primers induced restriction sites in normal DNA but not in mutational DNA. Genomic DNAs were extracted from paraffin-embedded tissues and were amplified with nested PCR. Among 17 cases, point mutation has not been able to be found so far, when examined in codon 12 of N-ras gene and among 10 cases in codon 61 of N-ras gene. It can thus be said that point mutational activation of N-ras oncogene is an uncommon event in human gliomas.

Base Sequence

[Planning for brachytherapy using a 3D-simulation model].

A 3D-simulation model made with a milling system was applied to HDR-brachytherapy. The 3D-simulation model is used to simulate the 3D-structure of the lesion and the surrounding organs before the actual catheterization for brachytherapy. The first case was recurrent prostatic cancer in a 61-year-old man. The other case was lymph node recurrence of a 71-year-old woman's upper gum cancer. In both cases, the 3D-simulation model was very useful to simulate the 3D-conformation, to plan the treatment process and to avoid the risk accompanying treatment.

Aged

[High dose rate fractionated interstitial radiotherapy for vulvar cancer using traction technique].

A 73-year-old woman with vulvar cancer T2NO was treated with high dose rate fractionated interstitial radiotherapy after 30 Gy of external radiotherapy. Sufficient space to insert 12 needles was made by pulling the vulva out perpendicular to the perineal skin. Four surgical threads were introduced between the vulva and the underlying pubic bones. A pair of custom-made templates were attached sandwiching the vulva pulled out with the threads. Using traction technique 12 stainless needles were easily inserted and replaced by plastic tubes. Forty Gy/10 fractions/six days was delivered, and the tumor has been controlled clinically and histologically so far.

Aged

Overall time in telecobalt therapy for T1 glottic carcinoma treated with 2 Gy per day.

BACKGROUND/AIM: We already reported the tumor response during radiotherapy as a prognostic factor for T1 glottic carcinoma. In these reports, we did not evaluate the overall treatment time. There were many reports of correlation between local control and overall treatment time of radiation for head and neck cancer. Our aim was to evaluate the overall treatment time as a prognostic factor of the local control for T1 glottic carcinoma or not. PATIENTS AND METHODS: From 1967 through 1985, 295 patients of T1 glottic carcinoma were treated with telecobalt therapy at the Department of Radiology, Osaka University Medical School. Of 295 patients, 219 patients treated with 2 Gy per day were evaluated. The median of total doses was 60 Gy (42 to 72 Gy). Overall treatment times of patients with tumor clearance at 40 Gy were significantly shorter than those with tumor persistence at 40 Gy. RESULTS: According to the univariate analysis, there were no statistically significant factors for local control except tumor response during treatment. Of 124 patients treated with a total dose of 60 Gy and the overall treatment time of 40 to 46 days, local control rates of patients treated with the overall treatment time of 40 to 42 days and 43 to 46 days were 88% and 78%, respectively (p = 0.3072). For 91 patients with tumor clearance at 40 Gy, local control rates of patients treated with the overall treatment time of 40 to 42 days and 43 to 46 days were 96% and 82%, respectively (p = 0.1645). Corresponding figures for 31 patients with tumor persistence at 40 Gy were 63% and 65%, respectively (p = 0.4227). CONCLUSION: We compare the treatment results of patients treated with the same total dose and the same tumor response during radiotherapy. We concluded that the overall treatment time was not a prognostic factor for T1 glottic tumor treated with overall time of 40 to 46 days.

Carcinoma

Human thrombin receptors are insensitive to thrombin-like snake venom enzymes.

Thrombin-like snake venoms enzymes, flavoxobin, and okinaxobin I isolated from Trimeresurus flavoviridis and Trimeresurus okinavensis, respectively, were examined in SH-EP cells and evaluated whether or not they can activate human thrombin receptors. Flavoxobin was almost completely inactive in both assays for phosphoinositide turnover and DNA synthesis. In contrast, okinaxobin I stimulated phosphoinositide turnover in a dose dependent manner, but considerably weakly. The EC50 value was about 100 nM, which was 4,000 times larger than that of alpha-thrombin. This stimulation was not inhibited by hirudin, an effective inhibitor of alpha-thrombin. Okinaxobin I also induced a very weak stimulation of DNA synthesis. These results suggest that thrombin-like snake venom enzymes interact with human thrombin receptors in inefficient ways. Weak interactions of the enzymes with thrombin receptor and inhibitor were ascribed to the incomplete formation of a lysine-cation cluster necessary for electrostatic molecular recognition.

Amino Acid Sequence

Nuclear characterization and G2M ploidy in human brain tumors using semiautomated image analysis.

We used image analysis to study nuclear morphometry and DNA content in relation to time to tumor progression in a series of 88 patients with brain tumors. Clinical follow-up was obtained for 73 patients. The patients with diploid tumors had a longer time to tumor progression than those with triploid, tetraploid, or hypertetraploid tumors. Mean SG2M-DNA indices (DIs) increased significantly with a increase in mean DIs in all tumors. The mean DIs appeared to be dependent on the number of SG2M phase cells. We conclude that tumors with hypertetraploid in G2M ploidy are highly malignant. Those tumor cells have a large nuclear size, much deformity in nuclear shape, and great proliferative potential. The G2M-tetraploid tumors showed a shorter time to tumor progression when the number of SG2M fractions was large. In contrast, the G2M-hypotetraploid tumors showed a longer time to tumor progression in comparison with other tetraploid and hypertetraploid tumors, but the difference was not significant.

Aneuploidy