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C Sakai

Publications and source records attributed to C Sakai.

At least 55 records · Page 3Linked to original sources
PubMed1995

Modulation of melanogenic protein expression during the switch from eu- to pheomelanogenesis.

Mammalian melanocytes can produce two basic types of melanin, eumelanin and pheomelanin, within discrete organelles termed melanosomes. The physiological signals that regulate this switch are extrinsic to the melanocyte, and include alpha-melanocyte stimulating hormone and the agouti protein. Tyrosinase, encoded at the albino locus, is the enzyme essential for the synthesis of both types of melanin, but other tyrosinase-related proteins (e.g. TRP1 encoded at the brown locus and TRP2 encoded at the slaty locus) regulate eumelanogenesis catalytically at steps distal to tyrosinase (as 5,6-dihydroxyindole-2-carboxylic acid oxidase and DOPAchrome tautomerase, respectively). The silver protein is another melanosomal protein, and although it has some limited homology to the tyrosinase-related proteins, it does not have any known enzymatic function and probably serves as a structural matrix protein. The role of each of those melanosomal proteins in pheomelanogenesis, however, is still unclear. In this study, we have compared the expression and catalytic functions of those proteins in pheomelanic and eumelanic hair bulb melanocytes. There was no detectable expression of TRP1 or TRP2, or either of their enzymatic activities, in hair bulbs of lethal yellow (Ay/a) newborn mice, and tyrosinase activity was present at a reduced level compared to that found in hair bulbs of black (a/a) newborn mice. Similar results were observed in regenerating hair bulbs of adult lethal yellow mice and in hair bulbs of 5- to 7-day-old agouti mice (A/A), an age where pheomelanin is produced predominantly. Expression of the silver protein was similarly not observed in hair bulbs of the pheomelanic mice.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Hemolytic-uremic syndrome due to deoxycoformycin: a report of the second case.

A hypercalcemic patient with adult T-cell leukemia was treated with deoxycoformycin (DCF) in a dose of 5 mg/m2 daily for three days. Several days later, severe thrombocytopenia appeared abruptly and then microangiopathic hemolytic anemia ensued. Subsequently, renal failure and hypertension developed, and the patient died seven weeks after DCF therapy. Needle necropsy of the kidney showed glomerular damage including swelling of endothelial cells, mesangiolysis and segmental collapse. This is the second reported case of hemolytic-uremic syndrome due to DCF.

Fatal Outcome↗
PubMed1995

[The effects of fitness-type exercise on iron status and hematological status for female college students].

Forty-two female college students underwent fitness-type exercise over a 13 week period. The students exercised an average of two times a week for 30 minute periods at 50% levels of VO2 . max. Iron status and hematological laboratory data were monitored at three points in time; at the initiation of exercise, at the termination of exercise and 3 months later. Serum ferritin levels in a third of the students were lower than 12ng/ml. Red blood cell counts decreased during exercise, and returned to the pre-exercise levels 3 months later. The number of circulatory reticulocytes and mean corpuscular hemoglobin concentration were increased significantly after the exercise and the effects were still observed 3 months later, independent of the iron status. In the lower ferritin group, erythropoietin levels decreased significantly during the post-exercise period. The average serum ferritin levels while showing no significant changes during exercise, increased significantly during the post-exercise period, in the normal ferritin group. We discussed possible mechanisms, among them iron metabolism, by which physical training may facilitate erythropoiesis. However, no definite conclusions have been reached.

Adult↗
PubMed1994

Functional analysis of the slaty gene product (TRP2) as dopachrome tautomerase and the effect of a point mutation on its catalytic function.

Slaty (slt), an autosomal recessive mutation that arose in YZ57/Ch mice, results in the dilution of coat color and premature hair loss. Recently, a gene encoding a homologue of the melanogenic enzyme tyrosinase (termed tyrosinase related protein 2 or TRP2) was cloned and was subsequently mapped to the slaty locus on chromosome 14. TRP2 was shown to function in melanogenesis as DOPAchrome tautomerase by means of the catalytic activity of the immunopurified protein and in slaty mutant skin samples. In this study, we generated an expression vector of a murine TRP2 encoding cDNA and are able to confirm its activity as DOPAchrome tautomerase. We further demonstrate that the slaty mutation dramatically decreases the catalytic function of the protein.

Animals↗
PubMed1994

Coping and marital support as correlates of tinnitus disability.

Although there is increasing awareness that depression can add significantly to the disability associated with chronic medical illness, it is not clear whether all of the impact of psychosocial factors upon medical disability are mediated by or moderated by depression. It has not been determined whether treating depression alone is an adequate strategy for addressing psychosocial magnification of medical disability. We analyzed data collected at initiation of a treatment trial from 92 subjects with chronic severe tinnitus to assess the role of coping, and 49 subject-spouse pairs to assess the role of marital interaction in tinnitus-related role dysfunction. Three multiple regression models were developed. After accounting for gender, tinnitus loudness, and depressive severity among the 92 subjects, greater role dysfunction was associated appraisal of tinnitus as salient, and less role dysfunction with coping through avoidance or seeking social support. Marital interaction was assessed from patient and spouse perspectives. In the patient-rated set, less marital cohesion was associated with greater tinnitus-related role dysfunction. In the spouse-rated set, more punishing responses to subject illness behavior were associated with greater tinnitus-related role dysfunction. In each case the disabling effect was greater in the face of high levels of subject depression. This study provides evidence for the oft-stated analogy between chronic tinnitus and chronic pain, and provides justification for a similar multimodal treatment strategy. Reducing depression is an important means to reduce medical disability but should be supplemented by clinical attention to appraisal of the illness, modes of coping with the illness, and spousal response to the illness.

Adaptation, Psychological↗
PubMed1994

Malignant pheochromocytoma accompanied by microangiopathic hemolytic anemia: a case report.

A 63-year-old woman was in hospital for persistent backache. Four months prior to admission she had been pointed out as having hypertension for the first time. On admission, she had anemia (hemoglobin 7.0 g/dl) with reticulocytosis, and a blood smear showed fragmented erythrocytes. A bone marrow aspirate disclosed erythroid hyperplasia and invasion of cancer cells. The chest roentgenogram showed a coin-lesion of the right lung and left pleural effusion. A diagnosis of microangiopathic hemolytic anemia (MAHA) associated with carcinomatosis was made, but the primary site of the cancer was unknown. Respiratory failure developed and the patient died a month later. Surprisingly, the autopsy revealed a malignant pheochromocytoma arising from the right adrenal gland with massive metastases to the lungs, liver, lymph nodes and systemic bones, and also disseminated intravascular coagulation (DIC). The DIC would probably account for the MAHA in this case. To our knowledge, this is the first reported case of malignant pheochromocytoma accompanied by MAHA.

Adrenal Gland Neoplasms↗
PubMed1993

A randomized trial of nortriptyline for severe chronic tinnitus. Effects on depression, disability, and tinnitus symptoms.

OBJECTIVE: To determine whether the antidepressant, nortriptyline, is effective for treatment of depression, tinnitus-related disability, and tinnitus symptoms in patients with severe chronic tinnitus. DESIGN: A 12-week, double-blind, randomized controlled trial. SETTING: A university otolaryngology clinic. PATIENTS: Ninety-two subjects with severe chronic tinnitus: 38 with current major depression and 54 with depressive symptoms and significant tinnitus-related disability. INTERVENTION: Nortriptyline (maintained at 50 to 150 mg/mL for 6 weeks) or placebo. MAIN OUTCOME MEASURES: Hamilton Depression Rating Scale, Tinnitus Disability Measures, and Audiometric Measures. RESULTS: Nortriptyline was superior to placebo by multivariate analysis of covariance for depression (10.6 vs 14.3 final Hamilton Depression score), for tinnitus-related disability (1.8 vs 2.4 final MPI Tinnitus Interference), and tinnitus loudness (13.6 vs 20.0 dB final loudness match [in worst ear at tinnitus frequency]). When major depression and depressive symptoms groups were considered separately, nortriptyline was superior to placebo on these same measures but differences did not achieve statistical significance. CONCLUSIONS: The antidepressant nortriptyline decreases depression, functional disability, and tinnitus loudness associated with severe chronic tinnitus. What appears to be irreversible disability of otologic origin may, in part, be reversible disability of psychiatric origin.

Aged↗
PubMed1993

Depressive symptoms and measures of disability: a prospective study.

OBJECTIVE: The purpose of this study was to test the hypothesis that decreases in severity of depressive symptoms in patients with chronic tinnitus would correlate with reductions in measures of functional disability. METHOD: This study describes the correlations between several measures of functional disability and Hamilton depression scores in two groups of patients with major depression and depressive symptoms (D-NOS) who were patients enrolled in a 12-week placebo-controlled, double-blind trial of nortriptyline. These patients had chronic severe tinnitus which was associated in most patients with high frequency hearing loss. The effect of whether affective symptoms improved and the patient's initial depression status (major depression versus depressive symptoms) are examined in order to increase understanding about the correlations between depressive symptoms and functional disability. RESULTS: Most measures of functional disability decreased synchronously with Hamilton Depression Scale scores in both patients with major depression and those with subclinical depressive symptoms. Patients whose depression improved had a significantly greater change in each disability measure than patients whose depression did not improve. This significant decrease in functional disability was seen in 11 of 13 scales in the improved D-NOS group, versus only 3 of the 13 scales in the unimproved D-NOS group; 9 of 13 scales of functional disability significantly decreased in the improved major depression group, versus 3 of 13 scales in the unimproved major depression group. CONCLUSIONS: The results suggest that there was a significant correlation between improvement in both major depression and depression-NOS symptoms, and decreases in measures of functional disability in an aging population with a chronic medical illness.

Adaptation, Psychological↗
PubMed1993

Pigment production in murine melanoma cells is regulated by tyrosinase, tyrosinase-related protein 1 (TRP1), DOPAchrome tautomerase (TRP2), and a melanogenic inhibitor.

Using antibodies that recognize either tyrosinase, tyrosinase-related protein-1 (TRP1), or tyrosinase-related protein-2 (TRP2, DOPAchrome tautomerase), the quantities of those melanogenic enzymes were analyzed in five melanoma cell lines that possess various degrees of melanin production. All cells except JB/MS-W increased melanin production four to 30 times after 4 d of melanocyte-stimulating hormone (MSH) treatment. Melanin production by JB/MS-W cells was always under background, with or without MSH treatment. There was a positive correlation between quantities and synthetic rates of those melanogenic enzymes and their melanin formation or DOPAchrome tautomerase activities. The activity of a heat-resistant melanogenic inhibitory factor was also analyzed. The results showed, surprisingly, that pigmented cells showed higher levels of melanogenic inhibitors activity. Tyrosinase activity was increased dramatically whereas the level of melanogenic inhibitor was remarkably decreased following MSH treatment. Interestingly, melanogenic inhibitor derived from JB/MS-W cells suppressed not only tyrosinase but also DOPAchrome tautomerase, another enzyme functional in melanin production. These results clearly suggest that melanin production is regulated by a subtle balance between the activities of these enzymes and other factors such as the melanogenic inhibitor.

Animals↗
PubMed1993

Erythroderma and marked atypical lymphocytosis mimicking cutaneous T-cell lymphoma probably caused by phenobarbital.

A 56-year-old man had been treated with phenobarbital seven weeks prior to admission. One month after initiation of administration of phenobarbital, fever, skin rash and lymphadenopathy occurred. Nine days later, marked atypical lymphocytosis, eosinophilia and hepatic injury was noticed. The histology of the biopsied skin was indistinguishable from lymphoma. CHOP-therapy was started but the patient was followed without further treatment because of polyclonal T-lymphocytosis. Afterward, clinical and hematologic improvement ensued and he has been well until now, 52 months later. The marked T-lymphocytosis observed in this case is probably a lymphoid leukemoid reaction secondary to hypersensitivity to phenobarbital.

Dermatitis, Exfoliative↗
PubMed1993

[Alternating CHOP-MEVP chemotherapy for advanced-stage, intermediate- and high-grade non-Hodgkin's lymphomas].

Twenty-one patients with advanced-stage, intermediate- and high-grade non-Hodgkin's lymphomas were treated with alternating CHOP-MEVP chemotherapy. CHOP therapy consisted of CPA 650 mg/m2, ADM 45 mg/m2, VCR 1.4 mg/m2 and Pred 40 mg/m2 (po). MEVP therapy consisted of MIT 10 mg/m2 (iv) VDS 2 mg/m2 (iv) on day 1, etoposide 200 mg/m2 (po) on days 1-3, and Pred 40 mg/m2 (po) on days 1-5. Three courses of CHOP therapy and MEVP therapy were alternatively administered every three weeks. CR was achieved in 15 (71.4%) of 21 patients. Survival rate and relapse-free rate at 2 years for all 21 patients were 61.9% and 30.9%, respectively. Toxicity was generally tolerable except for CMV interstitial pneumonitis in a patient with IBL-like T-cell lymphoma and secondary leukemia in a patient with T-cell lymphoma. Chemotherapy of higher dose intensity is required to improve the relapse-free survival rate in these subsets of lymphoma.

Adult↗
PubMed1993

[A fatal case of a hepatitis B virus carrier with fulminant hepatic failure after cytotoxic chemotherapy for malignant lymphoma].

A 48-year-old woman with malignant lymphoma, who was diagnosed as a hepatitis B virus (HBV) carrier because of positive HBs antigen, was admitted to Chiba Cancer Center Hospital. Complete remission was achieved by two courses of combination chemotherapy, but fulminant hepatitis developed after withdrawal of chemotherapy and she died of hepatic failure. Retrospective analysis of viral DNA disclosed a mutation in the precore region of HBV-DNA in her serum. We consider that the precoremutant virus was associated with the pathogenesis of severe hepatic failure after withdrawal of cytotoxic chemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

A comparative study of CHOP versus MEVP (mitoxantrone, etoposide, vindesine, prednisolone) therapy for intermediate-grade and high-grade non-Hodgkin's lymphoma: a prospective randomized study.

To evaluate a new combination chemotherapy with mitoxantrone (MXT), etoposide (VP-16), vindesine (VDS), and prednisolone (MEVP therapy) as a front-line chemotherapy for non-Hodgkin's lymphoma (NHL), a prospective randomized study comparing this therapy (28 patients) with CHOP therapy (29 patients) was conducted in 57 patients with intermediate-grade or high-grade NHL with stages II-IV. The MEVP therapy consisted of 10 mg/m2 of MXT intravenously on day 1, 2 mg/m2 of VDS intravenously on day 1, 200 mg/m2 of VP-16 orally on days 1-3, and 40 mg/m2 of prednisolone orally on days 1-5. This regimen was repeated every 3 weeks for up to 10 courses. Complete responses (CR) were achieved in 17 (63.0%) of the 27 evaluable patients treated with MEVP therapy, and in 20 (71.4%) of the 28 evaluable patients treated with CHOP therapy. Relapse-free survival rates and overall survival rates at 3 years were 58.8% and 46.4%, respectively, for the MEVP group and 70.0% and 54.0%, respectively, for the CHOP group. Granulocytopenia was more severer and associated infection episodes were more frequent in the MEVP group. MEVP therapy was effective as a front-line chemotherapy for intermediate- and high-grade NHL, although it was not superior to CHOP therapy in treatment effect and was not less toxic than CHOP.

Adolescent↗
PubMed1992

[THP-adriamycin-based combination chemotherapy in the treatment of non-Hodgkin's lymphoma].

Thirty patients with non-Hodgkin's lymphoma were treated with THP-adriamycin-based combination chemotherapy. Complete remission was obtained in eighteen (72%) of 25 evaluable patients. Nine of 18 patients are still alive in complete remission lasting 9 to 34 months (median 24 mo). Severe side effects such as bone marrow suppression, gastrointestinal symptoms and cardiotoxicity were rare. It was concluded that THP-adriamycin-based combination chemotherapy is relatively mild and safe, so this regimen is useful for elderly patients or patients with complications.

Adult↗
PubMed1992

[BH-AC.nitrosourea-therapy for refractory or relapsed malignant lymphoma].

Thirty patients with refractory or relapsed non-Hodgkin's lymphoma were treated with behenoyl ara-C (BH-AC) and nitrosoureas. Sixteen patients (53%) had a diffuse, large cell lymphoma and 22 patients (73%) had a stage IV disease. BH-AC, 250 mg/body, in combination with ACNU or MCNU, 50 mg/body, was administered by drip infusion for two days (Day 1, 2) every 3 to 4 weeks. Six patients (20%), all of them relapsed cases of diffuse lymphoma, obtained complete remission lasting one to six (mean: 2.5) months and 15 patients (50%) obtained partial remission lasting one to five (mean: 2.7) months. The major side effect was thrombocytopenia, and nine patients (30%) had required platelet-transfusions. There was no case complicated by infection due to prolonged neutropenia. Therefore, we conclude that BH-AC.Nitrosourea-therapy is very useful for the salvage chemotherapy of malignant lymphoma.

Adult↗