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Biomedical subjects

K Ishitani

Publications and source records attributed to K Ishitani.

At least 19 recordsLinked to original sources

The cell surface-expressed HSC70-like molecule preferentially reacts with the rat T-cell receptor Vdelta6 family.

We previously showed that the cell surface-expressed Mr 70,000 heat shock cognate (hsc70, a constitutively expressed member of the hsp70 family) protein-like molecule (#067 molecule) interacts with rat CD3+, CD4-, CD8-, T-cell receptor (TCR)alphabeta-, natural killer recetor-P1- T cells. This 70hsc-like molecule was also suggested to present cellular peptide antigens to these T cells. In the present study, we identified the genetic structure of the TCR by establishing T-cell hybridomas between these T cells and mouse BW5147 cells. Our data indicated that these T cells preferentially used TCRs with the Vdelta6 family. Analysis of the nucleotide sequence of the CDR3 junctional portion showed that there are substantial diversities, with insertion of seven to nine amino acid residues. These data provide indirect evidences for our hypothesis that an hsc70-like molecule could be presented together with cellular peptide antigens to particular T cells with TCR gammadelta chains. Since the expression of this hsc70-like #067 antigen on the cell surface is usually induced along with cell transformation by activated oncogenes, T cells with the TCR Vdelta6 family are likely to contribute to host resistance to tumor cells.

Amino Acid Sequence↗

Successful treatment of a case of relapsed acute promyelocytic leukemia with arsenic trioxide.

We report a patient with an initial relapse of acute promyelocytic leukemia (APL) who achieved a second complete remission (CR) after treatment with arsenic trioxide. The patient, a 66-year-old woman diagnosed as having relapsed APL, received arsenic trioxide intravenously at a dose of 10 mg/day. At day 36, the patient achieved a second CR. The side effects were slight neuralgia and mild skin erythematous changes, which improved following cessation of the drug. Although arsenic trioxide may be effective for relapsed APL, it should be used with caution because of various complications.

Aged↗

Calcium absorption from the ingestion of coral-derived calcium by humans.

Recent dietary life involves frequent opportunities for the ingestion of purified, processed food products and preserved foods, and it has been pointed out that the current dietary mineral intake strongly tends toward nutritional imbalance. The Ryukyu Islands yield coral which contains calcium and magnesium in a content ratio of about 2 to 1, with their approximate contents of 20 and 10%, respectively. In this report, the calcium absorption from the ingestion of crackers into which the coral powder was incorporated (coral-added crackers) and that from ingestion of calcium carbonate-added crackers was comparatively assessed. Twelve healthy adult volunteers (6 men and 6 women) ingested coral-added crackers (calcium content: 525 mg) and calcium carbonate-added crackers (ditto) once each alternately on a cross-over design with a wash-out period of 3 d between the regimens. The study also included controls receiving neither cracker. The degree of intestinal absorption of calcium from coral-added crackers and that from calcium carbonate-added crackers was evaluated in terms of increment in urinary calcium excretion per dL of glomerular filtrate (GF) (difference between coral calcium and calcium carbonate) and increase in urinary calcium excretion per milligram creatinine (difference from control value). The increment in urinary calcium excretion per dL of GF during the latter half of the observation period after the ingestion of coral-added crackers was significantly greater than that during the latter half of the observation period after ingestion of calcium carbonate-added crackers (p = 0.039, paired t-test). A significant difference (from control value) in the increase of urinary calcium excretion per milligram creatinine was also observed (p = 0.0008). The present data, though from a relatively few study subjects, suggest that the calcium of coral origin is better absorbed from the intestine than calcium of calcium carbonate origin on the average.

Adult↗

[Progress in palliative medicine].

The major factors in the progress in palliative medicine in Japan are the hospice movement, as represented by the activities of the Japanese Association for Clinical Research on Death and Dying, and interdisciplinary research on the quality of life (QOL), particularly in the field of clinical oncology. Palliative medicine as a new paradigm today encompasses the fields of biology, psychology, sociology, and ethics, all of which are making steady progress under the banner of evidence-based medicine. In recent years, the problems of euthanasia and physician-assisted suicide, subjects of great debate and public concern, especially in America and European countries, have been studied in the field of psycho-oncology and continue to attract considerable attention. The relationship between depression and social supports is said to be of particular importance. The American Society of Clinical Oncology (ASCO) has made a positive statement to the effect that it would not hesitate in confronting the so-called "end-of-life" issue. All of these global trends point to the increasing importance of palliative medicine.

Hospices↗

[A case of advanced ovarian clear cell adenocarcinoma responding to cisplatin-cyclophosphamide and paclitaxel-carboplatin].

We report a case of stage IV ovarian clear cell adenocarcinoma successfully controlled by a combination of cisplatin-cyclophosphamide (CP) and paclitaxel-carboplatin (TJ). A 64-year-old female with advanced ovarian cancer and pleural effusion underwent 4 courses of combination chemotherapy with CP. The giant ovarian tumor showed a relative reduction in size and the pleural effusion disappeared. Serum CA-125 levels and CA 19-9 levels markedly decreased. Thus, the patient underwent a total hysterectomy and bilateral salphingoophorectomy. During the operation, a giant ovarian clear cell adenocarcinoma was found, but there was no peritoneal dissemination and no cancer cells in her peritoneal fluid. Thereafter, she underwent 3 courses of combination chemotherapy with TJ. She has had 13 months of stable, tumor-free survival since the operation and normal serum CA-125 and CA 19-9 levels. Ovarian clear cell adenocarcinoma generally responds poorly to cisplatin and carboplatin, but in combination chemotherapy with paclitaxel-carboplatin these may be effective.

Adenocarcinoma, Clear Cell↗

Psychiatric morbidity in terminally ill cancer patients. A prospective study.

BACKGROUND: In the study by Derogatis et al., which included patients with all stages of cancer, 47% of the patients met the DSM-III criteria for a psychiatric disorder, with adjustment disorders being the most common. Although the cancer stage is one factor that influences the nature and incidence of psychiatric disorders, no study has demonstrated the extensive range of psychiatric disorders in terminally ill cancer patients. METHODS: Ninety-three terminally ill cancer patients were systematically assessed using the Mini-Mental State Examination (MMSE) and Structured Clinical Interview for DSM-III-R (SCID) within 1 week of admission. RESULTS: Of this sample population, 53.7% met the DSM-III-R criteria for a psychiatric disorder and 42% had a cognitive impairment. Delirium was observed in 26 patients (28%), dementia in 10 (10.7%), adjustment disorders in 7 (7.5%), amnestic disorder and major depression in 3 (3.2%), and a generalized anxiety disorder in 1 (1.1%). CONCLUSIONS: This preliminary investigation of the prevalence of psychiatric disorders in terminally ill cancer patients showed that more than half of the patients met the criteria for a DSM-III-R psychiatric disorder; delirium was the most common type of psychiatric disturbance. Further prospective trials are critically important to establishing treatment modalities that promote the psychiatric well-being of patients with terminal illnesses.

Aged↗

[Importance of oral and dental care in home medical care].

Recently, the importance of home medical care has been stressed. But patients, those assisting them and home care nurses do not attach much importance to oral and dental care in home medical care. When we visit patients who have asked for dental treatment through home care nurses, they appeared to have very poor oral hygiene; cavities were uncared for, dental plaque and dental calculus built up, and they used ill-fitting dentures. Through home dental care visits, it was not just the dental treatment but advice on dental hygiene management and diet that helped patients regain their appetite and bring back a smile to their face, while giving a rhythm to their life. This created a certain human feeling and brought about better patient quality of life (QOL), while at the same time helping to improve the QOL of the family as well.

Delivery of Health Care↗

Auranofin inhibits calcium uptake into opsonized-zymosan-stimulated neutrophils obtained from rats.

In order to study the pharmacological action site of auranofin during the functional suppression of leukocytes, especially neutrophils, we investigated the influence of auranofin on the calcium-45 (45Ca2+) uptake into peripheral blood neutrophils and peritoneal resident macrophages isolated from normal and adjuvant-induced arthritis (AA) rats. Calcium-45 uptake into neutrophils and macrophages obtained from normal and AA rats was increased by stimulation with opsonized-zymosan, while auranofin inhibited the increase in the 45Ca2+ uptake into neutrophils, but not into macrophages. There was a tendency that auranofin more strongly inhibited the increase in the 45Ca2+ uptake into neutrophils obtained from AA rats than normal rats, but no statistically significant difference between them was observed in the inhibitory potency of auranofin. From these results, it is suggested that auranofin would show anti-rheumatic and anti-inflammatory effects by the inhibition of Ca2+ uptake into neutrophils which infiltrate into local lesions during the early and active phases of rheumatoid arthritis.

Animals↗

Intracellular Ca2+ responses induced by acetylcholine in the submucosal nasal gland acinar cells in guinea pigs.

We examined intracellular Ca2+ responses of the nasal gland acinar cells to clarify cellular responses and molecular events with regard to the regulatory mechanism of the nasal secretion. The acinar cells of the serous gland in the nasal septum of guinea pigs were obtained by meticulous and selective dissection with minimal contamination by epithelial lining cells after collagenase treatment. The dispersed acini were incubated in the oxygenated solution supplemented with fura 2 acetoxymethyl ester, and the intracellular Ca2+ concentration ([Ca2+]i) was measured by fluorescence ratio imaging microscopy. The application of acetylcholine (ACh) to the cells induced an initially rapid increased [Ca2+]i followed by a sustained plateau. The increase in [Ca2+]i induced by ACh was concentration dependent, ranging between 10(-8) and 10(-4) M. The [Ca2+]i response was completely inhibited by atropine, further indicating the involvement of muscarinic cholinergic receptors. Removal of external Ca2+ with addition of EGTA resulted in a transient increase without a sustained phase, and the transient increase was abolished by the intracellular Ca2+ antagonist 8-(diethylamino)-octyl-3,4,5-trimethoxybenzoate, indicating that this increase in [Ca2+]i was due to release from internal stores. The initial peak was not altered by changes in external pH, addition of adenosine 3',5'-cyclic monophosphate (cAMP), nor addition of phorbol 12-myristate 13-acetate (PMA) but was augmented by external K(+)-induced depolarization, suggesting that the transient increase was due to a changing in the binding affinity to inositol 1,4,5-trisphosphate. The sustained Ca2+ entry induced by ACh was inhibited by Ni2+, but not by nifedipine.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗

Xanthine derivatives inhibit the increase in intracellular Ca2+ concentration induced by acetylcholine in nasal gland acinar cells of the guinea-pig.

Intracellular calcium is considered to play a major role in secretory responses of various exocrine cell types. We examined whether xanthine derivatives can inhibit Ca2+ mobilization and entry in secretory cells in the airways. Therefore, the inhibitory effect of xanthines in the intracellular Ca2+ concentration ([Ca2+]i) in the isolated submucosal acinar cells of the guinea-pig nasal septum was investigated by means of fluorescence ratio microscopy. The inhibitory effects on Ca2+ release from stores was examined in Ca(2+)-free conditions. Effects on Ca2+ entry were estimated by two different protocols; 1) the sustained phase in a long-term application of acetylcholine (ACh) and 2) the [Ca2+]i overshoot following removal of ACh in Ca(2+)-free conditions. Xanthine derivatives, 3-isobutyl-1-methyl-xanthine (IBMX), caffeine, and theophylline, significantly inhibited the increase in [Ca2+]i evoked by ACh; both mobilization from internal Ca2+ stores and Ca2+ entry from the external space. The rank order of potency of these xanthine derivatives was IBMX > theophylline > caffeine. The addition of dibutyryl-cyclic adenosine monophosphate (cAMP) and forskolin to nasal gland acinar cells failed to inhibit the ACh-evoked increase in [Ca2+]i. Furthermore, a protein kinase A inhibitor, H-89, did not affect the inhibitory effect of the xanthine derivatives. The action of xanthines on the present acinar cells did not involve Ca(2+)-induced Ca2+ release (CICR) or an interaction with purinergic receptors. Thus, xanthines have a direct inhibitory effect both on Ca2+ release and entry in nasal gland acinar cells, and might thereby have antisecretory activity within the airways.

Acetylcholine↗

[The present situation and problems of home care for advanced cancer patients].

An attempt to introduce home care for advanced cancer patients has started throughout Japan. However, there are many problems which prevent its development into an established medical care system. We conducted a nationwide survey on the current situation surrounding home care for advanced cancer patients. We selected 20 hospitals around the country and examined 268 cases. The categories surveyed were: type of cancer; medical care system; medical treatment; informed consent; and the patient's death at home. The result shows that cancer of the colon, stomach, breast and lungs are the most prevalent forms of cancer. In some cases the team approach organized mainly by doctors and nurses was introduced, though to limited extent. The most common forms of treatment were chemotherapy, pain management and nutrition control. At the same time, many hospitals tried to establish a system which focuses on QOL. Informed consent was obtained in 60% of the cases and 10% of the patients died at home. According to our survey, a medical care system incorporating traditional home care (hospice home care) and high-technology home care is being pursued in Japan. The insufficiency of the home care system and the lack of education leading to qualification for clinical oncologists and oncology nurses are the most significant problems.

Home Care Services, Hospital-Based↗

Effect of trimebutine maleate on the contractile response of the isolated ileum from diabetic rats.

1. Tension of the isolated ileum from diabetic rats induced by streptozotocin was measured isometrically to study the mode of action of trimebutine maleate (TMB). 2. The hyperreactivity of contractile response to KCl was observed in the isolated ileum from diabetic rats. TMB inhibited the contraction induced by KCl and acetylcholine (ACh) in normal solution. 3. In Ca2+ free solution, the hyperreactivity of contractile response to KCl was attenuated, and TMB did not inhibit the contraction induced by KCl. In contrast, TMB inhibited the contraction induced by ACh even in Ca2+ free solution. 4. These results suggest that the hyperreactivity of contractile response to KCl in the ileum from diabetic rats is due to the enhancement of Ca2+ influx through voltage-dependent Ca2+ channel and that TMB inhibits the hyperreactivity of contractile response through the inhibition of Ca2+ movement by the cell.

Animals↗

[Phase I clinical trial of RP 56976 (docetaxel) a new anticancer drug].

A multicenter phase I clinical trial of RP 56976 (docetaxel), a new anticancer drug, was performed with single and repeated doses. Based on the results of phase I clinical trials conducted in the United States and Europe, the starting dose was 10 mg/m2. The dose was subsequently increased to 20, 50, 70 and 90 mg/m2. A dose of 60 mg/m2 was additionally tested. Single administrations of the six dose levels were performed in a total of 27 patients via intravenous drip infusion over one hour. Ten of the patients subsequently received repeated doses at three of the dose levels in the same manner. The dose limiting factor (DLF) of docetaxel is leukopenia (especially, neutropenia). Based on the observation of the DLF, the maximum tolerated dose (MTD) was determined to be 70-90 mg/m2. The white blood cell count reached a nadir about 9.5-19.5 days (median) after administration, and took 7-11 days (median) to recover. Other adverse reactions observed were nausea/vomiting anorexia, alopecia, diarrhea, fatigue and fever, which were all acceptable. The results of this trial suggest that a dosage regimen of 60 mg/m2 at 3- to 4 week intervals is appropriate in an early phase II clinical trial.

Adolescent↗

[Antitumor and anticachectic activity of UFT in BALB/c mice bearing colon 26 adenocarcinoma].

We established a cancer cachexia model in BALB/c mice bearing Colon 26 and examined antitumor and anticachectic activity of UFT. The mice bearing Colon 26 showed a progressive loss of body weight, loss of lipid, and hypalbuminosis associated with the change of tumor size and these symptoms were improved by removal of cancer. In this model UFT extended life span significantly at 15mg/kg/day though showed a little growth inhibitory activity. UFT showed a significant tumor growth inhibitory activity and extended life span at 20mg/kg/day and could reverse all biological parameters mentioned above. Since the intratumor and plasma contents of IL-6 were significantly lowered in the UFT administered group, it is estimated that the anticachectic activity of UFT originates from reduction of interleukin-6 in tumor.

Adenocarcinoma↗

[Quality of life for older people under oncological treatment].

Recently, an argument over the medical treatment of older patients has arisen in the field of clinical oncology. In the past oncological treatment has been geared to young and middle-aged people. Currently, oncological treatment takes the peculiarities of older people into consideration. Firstly, it highlights the multidimensionality of Quality of Life (QOL) as an important element, with subjectivity the second element. This notion has gained a worldwide consensus. The domain of "multidimensionality" consists of: 1. Physical status and functional abilities 2. Psychological status and well-being 3. Social interaction 4. Economic status and factors With these factors in mind, different questions are asked, depending on the condition of each patient, in order to let the patient form his/her own judgment on possible medical treatment. However, it is sometimes difficult for older people to make such judgments due to problems such as depression or their diminishing mental ability. Also, it is impossible to define life satisfaction indiscriminately without regard to individual outlook. QOL for older people is generally characterized by "individuality" which includes: 1) A person's integrity; 2) independence; and 3) autonomy. Though these elements are taken into account in adopting the above-mentioned methodology, the field of clinical oncology's two concepts of QOL still apply in principle. Flexibility to put emphasis on different elements of the domain will be necessary. Even though QOL for older people is a matter of subjective judgment, the "sound judgment of professionals" (objective and scientific judgment of caregivers) can be adopted in cases when there is difficulty in communication.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Induction of platelet-activating factor in mice by intravenous administration of a neutral fraction of bakers' yeast mannan.

A neutral subfraction of mannan of bakers' yeast (WNM) was found to show a lethal effect in mice when administered intravenously. Symptoms caused by intravenous (i.v.) administration of WNM resembled those resulting from the administration of platelet-activating factor (PAF). CV-3988 and ONO-6240, selective PAF antagonists, prevented hypotension and death caused by the administration of WNM or PAF. A beta-adrenoceptor agonist was shown to prevent death caused by WNM, whereas propranolol increased the lethal activity of WNM. Intravenous administration of WNM into mice produced PAF in gall bladder fluid which was determined by platelet aggregation assay. The findings indicate that WNM is able to induce PAF in mice and that the resultant PAF may participate in the WNM-induced lethal activity observed in mice.

Albuterol↗