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Biomedical subjects

Y Yamamura

Publications and source records attributed to Y Yamamura.

At least 91 records · Page 5Linked to original sources

[Preparation of ketamine tablets for treatment of patients with neuropathic pain].

Ketamine is known to have distinguished analgesic effects without anesthetic when administered in a low dose. Since ketamine is not commercially available except injection forms, we prepared ketamine tablets for the home-care medication of patients with neuropathic pain. The direct compression or wet granulation method was employed to form 150 mg of tablets containing 50 mg of ketamine. The latter method was superior to the former one in terms of content uniformity, weight variation and disintegration tests of the tablets. Ketamine contents in the tablet prepared by the wet granulation method were unchanged for 12 weeks under the conditions of 25 degrees C and 75% relative humidity (RH). The Cmax and AUC0-3 h values for ketamine after administration of the tablet were slightly smaller than those of the syrup in a healthy volunteer. However, analgesic effects of the tablet was similar to that of the syrup in a patient with neuropathic pain. And the tablet was also effective for another four patients with neuropathic pain. These results indicate that ketamine tablets are useful for the home-care medication of patients with neuropathic pain.

Adult↗

[Effects of the rational use of corticosteroids eye drops for the prevention of ocular toxicity in high-dose cytosine arabinoside therapy].

Although the use of corticosteroid (CS) eye drops of the use of eye washing by artificial tears was effective for the prevention of ocular toxicity such as keratitis and photophobia in the high-dose cytosine arabinoside (Ara-C) therapy, the toxicity was not prevented perfectly. We studied the effects of the rational use of CS eye drops, and the combined use of CS eye drops and eye washing by physiological saline in order to prevent the ocular toxicity. Before the study, the instillation of 0.1% sodium bethamethazone phosphate (BM) eye drops was carried out at 4-6 times per day during the high-dose Ara-C therapy, and continued for several days after the high-dose Ara-C therapy. However, the rational use of "eyelid closure" and "naso-lacrimal occlusion" after the instillation was not performed Consequently, the ocular toxicity was observed in 3 (19%) of 16 cases of the patients. When the instillation of BM eye drops at 4 times per day was carried out rationally according to the consultation of pharmacist during the high-dose Ara-C therapy and for additional 10 days after the therapy, no ocular toxicity was observed in all cases (0 of 6 cases). Furthermore, the combined use of eye washing by physiological saline and instillation of BM eye drops was effective for the decrease of the risk of ocular toxicity, because no ocular toxicity was observed in the high-dose Ara-C therapy (0 of 34 cases). Our procedure in this study would be effective for the prevention of ocular toxicity in the high-dose Ara-C therapy.

Adolescent↗

[Renal cell carcinoma with late skin metastasis: a case report].

An 81-year-old man complaining of appetite loss visited our clinic. Four subcutaneous nodules were visible. One was seen on the right chest, 1 on the left shoulder and 2 on the abdomen. They were soft, dome-like masses and 20 to 30 mm in diameter. Computed tomography revealed multiple metastatic lesions in the brain, lungs, abdomen and skin. The patient had undergone radical nephrectomy for renal cell carcinoma 15 years earlier. The histology of the biopsy specimens obtained at nephrectomy was grade 1 and that of the subcutaneous nodules was grade 2. The patient died 49 days after admission, in spite of interferon-alpha therapy. To our knowledge, this is the 63rd case of skin metastasis of renal cell carcinoma in Japanese literature.

Aged↗

Slowly progressive L-DOPA nonresponsive pure akinesia due to nigropallidal degeneration: a clinicopathological case study.

We report an autopsy case of a 51-year old man who showed slowly progressive pure akinesia: freezing phenomenon and festination during 21 years of illness without tremor, rigidity, upward gaze palsy, bradykinesia and dementia, which were not responded to L-DOPA clinically. Neuropathological findings revealed the circumscribed regions in the substantia nigra and middle portion of the internal globus pallidus (GPi), without neurofibrillary tangles, neuropil threads, and glial fibrillary tangles. So this case was clearly distinguished with progressive nuclear palsy and pallidonigroluisian atrophy. It was first reported to describe that L-DOPA nonresponsive pure akinesia can arise from nigopallidal atrophy.

Disease Progression↗

Point mutations (Thr240Arg and Gln311Stop) [correction of Thr240Arg and Ala311Stop] in the Parkin gene.

Autosomal recessive juvenile parkinsonism (AR-JP) is a distinct clinical and genetic entity characterized by selective degeneration of nigral neurons. Recently, the parkin gene responsible for AR-JP has been identified. To date, we found two different deletional mutations including single and multiple exonic deletions. In the present study, we identified two types of point mutations (Thr240Arg and Gln311Stop) involving exons 6 and 8 in the parkin gene of the AR-JP patients from two Turkish families. This is the first report on point mutations for the parkin gene. Furthermore, the Thr240Arg mutation was located on a consensus sequence for the site of phosphorylation by casein kinase II. Identification of its mutation provides an important clue as to the role of the Parkin protein in degeneration of the substantia nigra in the brain of AR-JP patients.

Adolescent↗

Prognostic value and clinical implications of disseminated cancer cells in the peritoneal cavity detected by reverse transcriptase-polymerase chain reaction and cytology.

Free cancer cells exfoliated from the cancer-invaded serosa contribute to peritoneal dissemination, the most frequent pattern of recurrence in gastric carcinoma patients. This study was designed to evaluate the prognostic relevance of such free cells in peritoneal washes detected by reverse transcriptase-polymerase chain reaction (RT-PCR) and cytology. RT-PCR analysis with primers specific for carcinoembryonic antigen and conventional cytologic examination by Papanicolaou staining were performed on peritoneal washes, collected at laparotomy from 148 gastric carcinoma patients. Prognostic analyses were performed with 1) death due to cancer recurrence and 2) peritoneal dissemination as endpoints. RT-PCR was found to be more sensitive than cytologic examination for detection of free cancer cells in the peritoneal washes, with a higher detection rate for each of the T categories in the tumor-node-metastasis (TNM) classification. Five patients with synchronous or recurrent peritoneal dissemination were found among 17 patients with positive RT-PCR and negative cytologic results. Both positive cytologic results and positive RT-PCR results had significant influences over the survival of patients with advanced gastric carcinomas (n = 75, p < .002). Detection of free cancer cells in peritoneal washes, most reliably by RT-PCR, is promising as a predictor of peritoneal dissemination in patients with gastric carcinoma.

Carcinoembryonic Antigen↗

Dual-tracer assessment of coupling between cardiac sympathetic neuronal function and downregulation of beta-receptors during development of hypertensive heart failure of rats.

BACKGROUND: Heart failure is associated with activation of the sympathetic nervous system and downregulation of beta-receptors. However, the coupling between cardiac sympathetic neuronal function and the beta-receptor during the development of hypertensive heart failure is not clear. METHODS AND RESULTS: We determined cardiac neuronal function and beta-receptors with a dual-tracer method of [131I]metaiodobenzylguanidine (MIBG) and 125I-cyanopindolol (ICYP) in Dahl salt-sensitive (DS) and salt-resistant (DR) rats. The rats were fed an 8% NaCl diet after the age of 6 weeks. Blood pressure was raised to >200 mm Hg at 12 weeks in DS rats and remained elevated until 18 weeks, but only slightly in DR rats. Left ventricular (LV) function of DS rats was preserved at 12 weeks but deteriorated at 18 weeks. Despite a 56% reduction of cardiac norepinephrine (NE) content at 12 weeks in DS rats, neither MIBG nor ICYP uptake in DS rats was different from that of DR rats. At 18 weeks, both MIBG and ICYP uptakes decreased, by 52% and 39%, respectively, in association with 71% reduction of cardiac NE, in DS rats. MIBG uptake of the LV was homogeneous at 6 weeks but was lower in the LV endocardial regions at 18 weeks in DS rats. CONCLUSIONS: The present results indicate that cardiac sympathetic neuronal function is relatively preserved at the compensated, hypertrophic stage of DS rats but deteriorates in association with beta-receptor downregulation at the failing stage. The cardiac neuronal dysfunction occurs heterogeneously. A combination of scintigraphic portrayal of beta-receptors with MIBG should provide valuable information regarding sympathetic nerve signaling in living hearts.

3-Iodobenzylguanidine↗

Family history and subsite of gastric cancer: data from a case-referent study in Japan.

A comparative case-referent study was conducted using data from the Hospital-Based Epidemiologic Research Program at Aichi Cancer Center (HERPACC) (Nagoya, Japan), with the aim of clarifying the effect of family history on gastric cancer by subsite. Our study comprised 995 histologically confirmed gastric cancer cases (180 cardia, 430 middle, 365 antrum and 20 unclassified) and a total of 43,846 non-cancer outpatients at Aichi Cancer Center Hospital between 1988 and 1995. Logistic regression was used to calculate odds ratios (ORs) for family history of gastric cancer and other cancers, adjusted for age, year and season at first hospital visit, habitual smoking, habitual alcohol drinking, regular physical exercise, preference for salty food and raw vegetable intake. In both genders, a positive family history of gastric cancer was associated with a moderate, but statistically significant increase in risk of gastric cancer [OR = 1.51, 95% confidence interval (95% CI) = 1.29-1.76], while no association was observed between the risk of gastric cancer and a family history of other cancers [OR = 0.97, 95% CI = 0.84-1.13]. OR increased for the middle and antrum parts of gastric cancer, but an increment for the cardiac part was observed only in those with a maternal history of gastric cancer. Our results suggest that the risk of gastric cancer in relation to family history varies by subsite and, furthermore, that the subsite-specific risk of gastric cancer is linked to a maternal history of gastric cancer.

Adult↗

Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism.

Parkinson's disease is a common neurodegenerative disease with complex clinical features. Autosomal recessive juvenile parkinsonism (AR-JP) maps to the long arm of chromosome 6 (6q25.2-q27) and is linked strongly to the markers D6S305 and D6S253; the former is deleted in one Japanese AR-JP patient. By positional cloning within this microdeletion, we have now isolated a complementary DNA done of 2,960 base pairs with a 1,395-base-pair open reading frame, encoding a protein of 465 amino acids with moderate similarity to ubiquitin at the amino terminus and a RING-finger motif at the carboxy terminus. The gene spans more than 500 kilobases and has 12 exons, five of which (exons 3-7) are deleted in the patient. Four other AR-JP patients from three unrelated families have a deletion affecting exon 4 alone. A 4.5-kilobase transcript that is expressed in many human tissues but is abundant in the brain, including the substantia nigra, is shorter in brain tissue from one of the groups of exon-4-deleted patients. Mutations in the newly identified gene appear to be responsible for the pathogenesis of AR-JP, and we have therefore named the protein product 'Parkin'.

Adult↗

A microdeletion of D6S305 in a family of autosomal recessive juvenile parkinsonism (PARK2).

A gene for autosomal recessive juvenile parkinsonism (ARJP; HGMW-approved symbol PARK2; MIM 600116) has recently been mapped to a 17-cM interval on chromosome 6q25.2-q27. We here report an inbred family with ARJP showing a perfect cosegregation with null allele for D6S305, which is a marker within the ARJP locus. We assigned the deletion within an interval between D6S1937 and AFMa155td9, which are 0 cM apart from each other and located on a single YAC clone. Two possibilities should be evaluated: (1) the deletion is polymorphic and linked to ARJP and (2) the deletion is pathogenic and contains both D6S305 and the ARJP gene (or a part of it). An exon search in a deleted segment or in the relatively small-sized genomic clones harboring D6S305 may enormously facilitate the cloning procedure of the ARJP gene.

Chromosome Deletion↗

Suppression of intracellular hydrogen peroxide generation and catalase levels in CD8+ T-lymphocytes from HIV+ individuals.

CD8+ T-lymphocytes from HIV+ individuals contain short telomeres, a sign of cell senescence. To test our hypothesis that the cell type is functionally defective in the biochemical indices related to cell proliferation, we investigated the profiles of intracellularly generated H2O2 levels with or without PMA as well as immunoreactive catalase levels using flow cytometric method. We observed that, in HIV+ but not in HIV- individuals, the constitutively generated H2O2 level was significantly lower in CD8+ T-cells compared with CD4+ T-cells. Importantly, activated effector CD8+CD28- cells showed remarkably low H2O2 levels compared with CD8+CD28+ cells, and the latter in HIV+ individuals also showed low levels. A similar defect of CD8+ cells of HIV+ individuals was also seen with H2O2 levels stimulated with PMA in the presence of a catalase inhibitor. Furthermore, the immunoreactive catalase content was lower in CD8+ cells compared with CD4+ cells only in HIV+ individuals. These results suggest that CD8+ T-lymphocytes are functionally defective with the constitutively generated and PMA-elicited levels of H2O2 and the corresponding scavenger. Diminished immunocompetence of HIV+ individuals may be caused, in part, by the functional defect of CD8+ T-cells.

Adult↗

Lymph node status assessment for gastric carcinoma: is the number of metastatic lymph nodes really practical as a parameter for N categories in the TNM Classification? Tumor Node Metastasis.

BACKGROUND AND OBJECTIVES: The anatomical extent of nodal metastasis has been replaced by the number of metastatic nodes as a key indicator of prognosis (pN categories) in the fifth edition of Tumor Node Metastasis Classification for gastric carcinoma by the International Union Against Cancer. The rate of metastatic nodes among all the nodes harvested is also a good prognostic factor. The object of this study is to evaluate which of the three parameters for the assessment of nodal status is the most appropriate for use in the stage classification. METHODS: Retrospective survival analyses were performed in 656 consecutive patients with advanced gastric carcinoma who underwent D2 lymphadenectomy and for whom histopathologic data of more than 20 lymph nodes were available. RESULTS: Although all three systems served well to classify the patients into distinct groups in terms of survival curves, stratification by the number of metastatic nodes was vulnerable to stage migration because of differences in the number of lymph nodes harvested. Such stage migration was not evident for the other two parameters. CONCLUSIONS: Lymph node metastatic rate can be recommended as an internationally applicable parameter for lymph node involvement of gastric carcinoma.

Adult↗

Mode of cell death in the rat metrial gland during peripartum regression.

In the rodent uterus, the metrial gland develops during midpregnancy and undergoes regression prior to parturation. The involution of the gland is reported to be accompanied by the loss of gland cells due to their death in situ. Cell death has been classified by using morphological criteria into two types: necrosis and apoptosis. To study the mechanism involved in the peripartum regression of the rat metrial gland, we examined the mode of cell death in the gland during the last week of gestation. We identified apoptotic cells in the regressing metrial gland by using DNA fragmentation, in situ DNA 3'-end labeling, and electron microscopy. Expression of progesterone receptor (PR) and estrogen receptor (ER) was also demonstrated by immunohistochemistry in the gland. The mean weight of metrial gland nodes decreased after day 18 of pregnancy. The apoptotic granulated metrial gland (GMG) cells that were detected by using the in situ DNA 3'-end labeling method were observed on day 16 of pregnancy, and they increased in number after day 20 of pregnancy. Intense fragmentation of DNA was also found from day 20 to day 22 of pregnancy. Electron microscopy demonstrated apoptotic GMG cells in the regressing metrial glands, confirming the results of the labeling studies. Immunohistochemical study revealed that expression of PR and ER, which were localized mainly in fibroblast-like stromal cells but not in GMG cells, was almost unchanged during late pregnancy. Apoptotic cell death is the major mode of rat metrial gland cell death in the peripartum loss of metrial gland cells.

Animals↗

Molecular genetic analysis of a novel Parkin gene in Japanese families with autosomal recessive juvenile parkinsonism: evidence for variable homozygous deletions in the Parkin gene in affected individuals.

Autosomal recessive juvenile parkinsonism (AR-JP) is a distinct clinical and genetic entity characterized by selective degeneration of nigral dopaminergic neurons and young-onset parkinsonism with remarkable response to levodopa. Recently, we mapped the gene locus for AR-JP to chromosome 6q25.2-q27 by linkage analysis and we identified a novel large gene, Parkin, consisting of 12 exons from this region; mutations of this gene were found to be the cause of AR-JP in two families. Now we report results of extensive molecular analysis on 34 affected individuals from 18 unrelated families with AR-JP. We found four different homozygous intragenic deletional mutations, involving exons 3 to 4, exon 3, exon 4, and exon 5 in 10 families (17 affected individuals). In addition to the exonic deletions, we identified a novel one-base deletion involving exon 5 in two families (2 affected individuals). All mutations so far found were deletional types in which large exonic deletion accounted for 50% (17 of 34) and the one-base deletion accounted for 6% (2/34); in the remaining, no homozygous mutations were found in the coding regions. Our findings indicate that loss of function of the Parkin protein results in the clinical phenotype of AR-JP and that subregions between introns 2 and 5 of the Parkin gene are mutational hot spots.

Amino Acid Sequence↗

A decrease in cerebral cortex intensity on T2-weighted with ageing images of normal subjects.

To determine the change in intensity in the cerebral cortex on T2-weighted MRI with ageing, we reviewed the T2-weighted images of 83 normal subjects and measured the signal intensity in the cerebral cortex in 30 subjects randomly selected from them. Low-intensity areas were more common in the cerebral cortex of the aged. The intensity of different cortical regions varied, and the intensity in the temporal and parietal to be decreased with ageing. Presumably, this change of the intensity reflects senile changes, although low intensity is not evident in the temporal cortex because of its high basal intensity level.

Aging↗