Search PubMed⌕ Search

Biomedical subjects

Y Hakamata

Publications and source records attributed to Y Hakamata.

At least 37 records · Page 2Linked to original sources
PubMed2000

Tamoxifen inhibits lipoprotein activity: in vivo and in vitro studies.

Tamoxifen, a nonsteroidal antiestrogenic antitumor agent, has weak estrogen-like effects on lipid metabolism, however, the mechanism remains unknown. We previously reported that tamoxifen decreases the activity of lipoprotein lipase (LPL), a key enzyme in triglyceride metabolism, in patients with breast cancer. This study evaluated the effect of tamoxifen on LPL activity in vitro and in vivo. In experiment 1, total cholesterol, triglyceride, adipose tissue weight, and LPL activity of post-heparin plasma were measured in ovariectomized female rats with and without tamoxifen treatment. In experiment 2, purified very-low-density lipoprotein (VLDL) and purified LPL were incubated with and without tamoxifen or estrogen, and the triglycerides in VLDL were measured using an enzymatic method. In experiment 1, total cholesterol and adipose tissue weight decreased significantly in tamoxifen-treated rats (p < 0.001 and p < 0.01, respectively). Triglyceride measurements were not significantly different between the two groups, however, the LPL activity was lower in tamoxifen-treated rats (p < 0.005). In experiment 2, triglycerides in VLDL were significantly higher after VLDL and LPL were incubated with tamoxifen and estrogen (p < 0.005). We concluded that tamoxifen inhibits the hydrolytic activity of LPL in vivo and in vitro. This mechanism may explain the elevated serum triglyceride levels in some patients treated with tamoxifen.

Animals↗
PubMed2000

Effects of dosing time and schedule on cisplatin-induced nephrotoxicity in rats.

Renal dysfunction induced by a single injection of cisplatin depends on the timing of the dose. However, the effects of repeated administration of cisplatin on time-dependent toxicity have not been evaluated despite the fact that in clinical practice high doses are repeatedly injected at intervals or low doses are administered daily. We studied chrononephrotoxicity in rats after weekly or daily cisplatin injections. Weekly high doses (5 mg kg(-1)) or daily low doses (1.2 mg kg(-1)) of cisplatin were injected at four time points (3, 9, 15 and 21 h after the light was turned on (HALO)) for 3 weeks. Changes in body weight after weekly cisplatin administration were independent of the timing of the doses. In the group that received daily cisplatin, the loss in body weight in the 3 HALO group was smaller than in animals receiving injections at 15 and 21 HALO (P < 0.05 and 0.001, respectively). The blood urea nitrogen and serum creatinine levels in the control rats showed a significant circadian change (peak at 15 HALO and trough at 9 HALO), but these parameters were markedly elevated in both trials and their circadian variations were disturbed. In conclusion, cisplatin-induced nephrotoxicity was the lowest at 3HALO compared with other time points of both dose regimens.

Animals↗
PubMed1999

[Aspergillosis following influenza A infection].

An 83-year-old man had an influenza-like upper respiratory infection that progressed to pneumonia and respiratory insufficiency during a period two weeks. After admission, anti-influenza A antibody increased 32-fold and antibiotic treatment had little effect on the pneumonia. Aspergillus antigen was detected from his serum and pleural effusion, however, culture of sputum was negative for aspergillus. Administration of amphotericin B reduced the serum level of aspergillus antigen, however he died due to the progression of respiratory insufficiency and bloody sputum. Aspergillus infection is generally thought to occur in immunocompromised hosts, but this patient had no apparent immunosuppressive conditions except for his age before the influenza A infection. His WBC and lymphocyte count temporally decreased to 2,000 x 10(6)/L (lymphocytes 160 x 10(6)/L) followed by aspergillus infection. This temporally reduction of lymphocytes is thought to have been responsible for the aspergillus infection. Complications of influenza infection are sometimes fatal and vaccination against influenza seems necessary in high risk individuals such as elderly people.

Aged↗
PubMed1998

Characterization of brain-type ryanodine receptor permanently expressed in Chinese hamster ovary cells.

To clarify a function of brain-type ryanodine receptor (RyR3) and its regulation, we established a stable cell line expressing rabbit RyR3 by transfection of Chinese hamster ovary cells (CHO cells) with the cDNA and investigated characteristics of the RyR3. Scatchard analysis of [3H]-ryanodine binding to the membrane from CHO cells expressing RyR3 showed two distinct binding sites. The Kd values of high and low affinity binding sites were 1.92 and 25.9 nM, respectively. [3H]-ryanodine binding to the membrane from CHO cells expressing RyR3 was dependent on pCa. Extracellular Ca2+ (2-10 mM) and high concentration (more than 30 mM) of caffeine activated the RyR3 in CHO cells and increased its intracellular Ca2+ concentration. The enhancement of [3H]-ryanodine binding to the membrane from CHO cells expressing RyR3 was observed by bromoeudistomin D (BED), a caffeine-like powerful Ca2+ releaser, at pCa 5.5. Stably expressed RyR3 in CHO is useful for characterization of its function.

Animals↗
PubMed1998

[Slowly progressive IDDM with rheumatoid arthritis and Hashimoto disease in high elderly].

We report a 79-year-old woman case of slowly progressive IDDM (SPIDDM) with rheumatoid arthritis (RA) and Hashimoto disease. High titer of anti-glutamic acid decarboxylase antibody (GAD) with a value of 16,400 U/ml (normal value: less than 5 U/ml) and deteriorated secretion of insulin, and clinical course led to the diagnosis of SPIDDM. Both anti-islet cell and anti-insulin antibodies were negative. One year prior to the diagnosis, at 78 years of age, she was newly diagnosed with NIDDM and had been medicated with sulfonylurea and voglibose, resulting her glucose levels well-controlled. Four months before admission, a gradual increase of plasma glucose was noticed, while oral hypoglycemic agents were fully administrated. On admission, her glycemic control was revealed as follows; a fasting blood glucose level of 458 mg/dl and an HbA1 C level of 14.3%. Urinary CPR was 22.5 micrograms day. Her insulin secretion was proved not to be induced with intravenous glucagon injection. Hyperinsulinemic euglycemic glucose clamp test showed the normal glucose uptake ratio; 9.5 mg/kg/min. Moderate doses of subcutaneous insulin (20 units daily) were effective on her diabetes control. She was newly diagnosed with Hashimoto disease that required thyroid hormone replacement 50 micrograms per day after having developed NIDDM. High titer of anti-thyroglobulin antibody (46.9 U/ml) and anti-thyroid peroxidase antibody (81.5 U/ml) were observed. The patient had been medicated for RA with anti-inflammatory drugs since her early seventieth. Rheumatoid factor was elevated to 127.7 IU/L and, anti-nuclear antibody (x 80) and anti-DNA antibody (x 80) were present. It may be of interest that a specific phenotype of HLA; A24 (9) and DR9 recognized to be susceptible to IDDM was detected in the high-elderly onset SPIDDM. Taken together HLA typing with her history of both RA and Hashimoto disease, our case may provide the information to the mechanism of pathogenesis of SPIDDM. Furthermore, to out knowledge, this is the first case of SPIDDM in the aged; 75-year-old or more.

Aged↗
PubMed1997

Molecular cloning and characterization of a human brain ryanodine receptor.

We have cloned and sequenced the cDNA of the human brain ryanodine receptor (RyR3), which is composed of 4866 amino acids and shares characteristic structural features with the rabbit RyR3. Northern blot analysis shows that the human RyR3 mRNA is abundantly expressed in hippocampus, caudate nucleus and amygdala as well as in skeletal muscle. The human RyR3 mRNA is also detected in several cell lines derived from human brain tumors. Functional expression of RyR3 and a chimeric RyR suggests that RyR3 forms a calcium-release channel with a very low Ca2+ sensitivity.

Animals↗
PubMed1997

Topographical analysis of cortical neuronal loss associated with disseminated selective neuronal necrosis and infarction after repeated ischemia.

A study was carried out of the distribution and density of the neurons remaining in the gerbil cerebral cortex following two 10-min periods of ischemia at either 3-, 5- or 48-h intervals. As the interval between the periods of ischemia increased, the ischemic injury was reduced from severe to milder infarction, and further from more to less intense disseminated selective neuronal necrosis. This model is suitable for studying the mechanisms of transition from selective neuronal necrosis to infarction at the threshold level of infarction.

Animals↗
PubMed1997

Ultrastructure of astrocytes associated with selective neuronal death of cerebral cortex after repeated ischemia.

Astrocytic swelling after ischemic insult has been considered a sign of parturbed cell viability. Investigations using cultured astrocytes and C6 glioma cells have revealed that viable astrocytes swell, spatially buffering various metabolites which are increased by the metabolic turmoil following ischemic insults. In the present study, we have studied the temporal profile of ultrastructural changes of astrocytes in the cerebral cortex associated with progressive selective neuronal, death where infarction is not induced. We occluded the left carotid artery of the Mongolian gerbil twice for 10 minutes at a 5 hr interval. In this model, following reperfusion, selective neuronal death progresses in the coronal section cut at the infundibular level. The whole brains of the sham operated control and postischemic animals were fixed by transcardiac perfusion of glutaraldehyde fixatives, at 15 min, 5 and 12 hr after the 2nd 10 min ischemia. Ultrathin sections including the 3rd and 5th cortical layers were prepared from the cut surface at the level of infundibulum. Mild swelling of astrocytic processes and perivascular end-feet was observed in the 15 min group. Glycogen granules were not prominent. In the 5 hr group, we found a few necrotic neurons disseminated in the cortex. All astrocytic cell processes were swollen with increased number of glycogen granules, especially marked in the perivascular end-feet. In the 12 hr group, necrotic neurons increased in number, astrocytic swelling was more extensive, and glycogen granules were evident in astrocytes. No cellular destruction was observed. We conclude: 1. Swelling progresses in astrocytes which however still remain viable and this process is associated with selective progression of neuronal death. 2. Glycogen granules increase in the swollen yet viable astrocytic cell processes.

Animals↗
PubMed1997

Brain edema associated with progressive selective neuronal death or impending infarction in the cerebral cortex.

This study examined the temporal profile of brain edema in the cerebral cortex associated with selective neuronal death or focal infarction after repeated ischemia at an intensity of ischemic insult just under and above the threshold level to induce infarction. The left carotid artery of adult gerbils was twice occluded for 10 min each time with a 5-hr interval between the blockages. In this model, focal infarction developed in coronal sections examined at the chiasmatic level (face A), whereas only selective neuronal death without infarction was found in the coronal section observed at the infundibular level (face B). In each animal, Evans blue (2%) was intravenously injected 1 hr prior to sacrifice as an indicator of blood-brain barrier (BBB) disruption. Brain edema was assessed by gravimetry in samples taken from both faces at 15 min, 5 hr, 12 hr, 24 hr, and 48 hr after the 2nd 10-min ischemia. Evans blue extravasated only in face A, corresponding to focal infarction at 24 and 48 hr after the 2nd 10-min ischemia. The specific gravities of the ischemic cortex of both faces decreased significantly from control at 15 min (P < 0.05) and had recovered by 5 hr after ischemia. By 12 hr, the specific gravities of both faces had again decreased significantly from the control values (P < 0.05), but did not differ significantly from each other. At 24 and 48 hr, the specific gravities of both faces were significantly lower than the control values (P < 0.01), and the specific gravity of face A was markedly lower than that of face B (P < 0.01). We concluded that in face B, where only selective neuronal death without infarction occurred only cytotoxic edema develops, whereas in face A, where infarction progresses, vasogenic edema develops in addition to cytotoxic edema.

Animals↗
PubMed1997

Response of the extramedullary lung plasmacytoma with pleural effusion to chemotherapy.

An elderly patient with extramedullary lung plasmacytoma and subsequent pleural effusion is described. The presence of abnormal plasma cells in the pleural fluid led to diagnosis. Histologically similar conditions such as multiple myeloma and solitary myeloma of bone were ruled out by clinical evaluation. These neoplasms usually occur in the head and neck area and are not characterized by paraprotein accumulation. Few cases in the lung have been reported. We describe a case of extramedullary plasmacytoma of the lung with plasmacytoma-induced pleural effusion and the presence of monoclonal paraprotein in both the serum and urine. Chemotherapy with melphalan was effective in reducing the size of the plasmacytoma, and pleurodesis was used to manage the pleural effusion.

Aged↗
PubMed1997

Antiandrogenic natural Diels--Alder-type adducts from Brosimum rubescens.

The isolation and structure elucidation of five novel natural Diels--Alder-type adducts, named palodesangrens A-E (1-5), from the Peruvian folk medicine known as "palo de sangre" (Brosimum rubescens) is described. The structures of the Diels--Alder adducts, consisting of chalcone derivatives and a prenylcoumarin, were elucidated by analysis of spectroscopic data including 2D NMR. Some of these compounds showed potent inhibitory activity towards 5 alpha-dihydrotestosterone (DHT) binding with an androgen receptor to form a DHT-receptor complex that causes androgen-dependent diseases.

5-alpha Reductase Inhibitors↗
PubMed1997

Antiandrogenic phenolic constituents from Dalbergia cochinchinensis.

Four new compounds, 9-hydroxy-6,7-dimethoxydalbergiquinol, 6-hydroxy-2,7-dimethoxyneoflavene, 6,4'-dihydroxy-7-methoxyflavan and 2,2',5-trihydroxy-4-methoxybenzophenone, in addition to eight known phenolic compounds including 7-hydroxy-6-methoxyflavone, have been isolated from the stems of Dalbergia cochinchinensis. Their structures were established by spectroscopic techniques including one- and two-dimensional NMR methods. The first two compounds showed potent inhibitory activity towards 5 alpha-dihydrotestosterone (DHT) which binds with an androgen receptor to form a DHT-receptor complex that causes androgen-dependent disease.

5-alpha Reductase Inhibitors↗
PubMed1996

[University education in geriatrics. Opinions of teaching staff on undergraduate education in gerontology and geriatric medicine].

Undergraduate education in gerontology and geriatric medicine has become more important because of a progressive increase in the aged population. To assess curricula in geriatric medicine and to survey the opinions of teaching staffs as to the ideal curriculum, a questionnaire was sent to professors of gerontology and geriatric medicine at 14 medical schools. Responses were obtained from all 14 professors. In all medical schools, students are given lectures in the fifth or sixth year, or both. The total number of hours for the lectures varied from a few hours to 40 hours, and contents of the lectures varied between schools. Medical staffs pointed out that little time is allocated to geriatric medicine. They also emphasized the importance of bedside teaching.

Curriculum↗
PubMed1996

[University education in geriatrics: medical students' understandings of gerontology and geriatric medicine].

With the rapid aging of Japan's population, medical professionals who specialize in geriatric medicine are in unprecedented demand. To meet that demand and to improve the curriculum for teaching geriatric medicine and gerontology in Japan, we surveyed medical students' understandings of these specialties. Students at 14 schools with classes in geriatric medicine and gerontology were surveyed. A questionnaire was sent to sixth-year medical students after their classes had ended. Questionnaires were collected from 849 students (60.1%) at ten medical schools (74.1%). One quarter (24.5%) of the students were satisfied with the contents of the classes in geriatric medicine and gerontology taught in their school, whereas 39.4% were not. These specialties encompass many fields of clinical and basic medicine, and many students found the lectures difficult to understand (41.4%). Inter-school comparisons of the results showed that students' strengths and weaknesses in the various areas of geriatric medicine reflected differences in the contents of the classes among the schools. Only 35.4% of students had ever visited hospitals or other health-related facilities for the elderly. Many students (58.8%) had never lived with elderly people. Most students (63.9%) wanted visits to health-care facilities for the elderly to be included in their regular curriculum. Medical students are conscious of the medical implications of the ageing of Japan's population; 13.2% had volunteered to work with the elderly.

Attitude of Health Personnel↗
PubMed1996

[University education in geriatrics: medical student's opinions on gerontology and geriatric medicine].

With the aging of Japan's population, physicians need to be aware of advances in geriatric medicine. To assess the status of geriatric medicine in undergraduate education, we surveyed of medical student's opinions on gerontology and geriatric medicine. A questionnaire was sent to six-year medical students at a total of 20 schools that did not include geriatric medicine in their curriculum. Responses were obtained from 950 students (47.6%) at 16 schools (80%). Almost half of the students (42%) had experiences in health care facilities for the elderly. Ten percent were content with their education in geriatric medicine education and 59% were not. A total of 41.4% felt that geriatric medicine is difficult because it involves many different subjects. Some students had experience as volunteers working with elderly people; they were aware of the aging of Japan's population, and felt that their training in basic geriatrics and in geriatric diseases was insufficient. A total of 56% agreed that all medical schools should have classes in geriatric medicine and 14% did not. Medical students in the schools without classes in geriatric medicine identified dementia (73%), cerebral vascular accidents (51%), cancer (24%) and osteoporosis (19%) as common in elderly people, with no differences between schools. The corresponding data for medical students in schools with classes in geriatric medicine were dementia (77%), cerebral vascular accidents (44%), osteoporosis (29%), and cancer (16%). Undergraduate medical students seem to be exposed to widely differing curricula with regard to geriatric medicine. We found a lack of uniformity in the teaching of gerontology and geriatric medicine to undergraduate medical students in Japan.

Education, Medical, Undergraduate↗
PubMed1996

[Undergraduate teaching of geriatric medicine in western countries--literature review].

To help plan for the future of undergraduate education in geriatric medicine in Japan, we reviewed the literature concerning undergraduate teaching of geriatric medicine in western countries. Undergraduate teaching in geriatric medicine in the UK is well developed: 22 of 25 universities have a full department of geriatric medicine. Training in geriatric medicine is mandatory in almost all universities. In contrast, geriatric medicine is an elective in most universities in the US. There is a shortage of geriatric medicine faculty in the US, which is similar to the situation in Japan. Clinical and basic research in geriatric medicine and gerontology should be encouraged to attract persons into this field.

Education, Medical, Undergraduate↗
PubMed1995

Transition from ischemic neuronal necrosis to infarction in repeated ischemia.

To study morphological changes in the cortex that follow repeated ischemia, one, two, and three 7-min unilateral occlusions of the carotid artery at 6-h intervals, and three, four, and five 7-min similar occlusions at 12-h intervals were produced in gerbils. Animals with one and two 7-min occlusions at 6-h intervals showed selective neuronal necrosis in the cortex; those with three 7-min occlusions at 6-h intervals showed focal infarction in the third layer of the cortex. Animals with three 7-min occlusions at 12-h intervals showed selective neuronal necrosis; those with four 7-min occlusions at 12-h intervals showed focal infarction in the third layer. In animals with five 7-min occlusions at 12 h intervals, infarction affecting all layers of the cortex was seen. Results of the present study indicate that cortical infarction occurred when a brief ischemic insult that does not cause any visible morphological damage in cortical neurons was inflicted repeatedly, and that development of infarction in the cortex following repeated episodes of ischemia depended on both the number of insults and the time intervals between them. This finding suggests that there is a threshold of infarction in repeated ischemia. In our model, various stages of ischemic brain injury could be achieved more easily than in transient ischemia by altering the number of insults or the intervals between them. This model is suitable for studying the pathophysiology on transition from ischemic neuronal necrosis to infarction.

Animals↗