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T Saida

Publications and source records attributed to T Saida.

At least 37 records · Page 2Linked to original sources

Loss of beta-catenin expression associated with disease progression in malignant melanoma.

BACKGROUND: beta-catenin plays a crucial role in the function of cell adhesion molecules and also participates in growth regulatory signalling pathways that may be involved in malignant transformation. OBJECTIVES: To examine beta-catenin expression in lesions of melanocytic origin for associations with clinicopathological markers of disease progression and for its significance as a predictor of disease recurrence and prognosis. METHODS: beta-catenin expression was examined by immunoperoxidase staining in 50 melanocytic naevi and 91 primary and 50 metastatic melanomas. RESULTS: beta-catenin was expressed in 96% of melanocytic naevi, in 94% and 65%, respectively, of radial and vertical growth phase primary melanomas, and in 38% of metastatic melanomas. Benign and malignant melanocytic lesions had distinct patterns of beta-catenin localization. Most lesions expressing beta-catenin exhibited cytoplasmic staining; however, over 40% of benign lesions also displayed nuclear staining, which was present only in 10% of primary and 15% of metastatic melanomas. Absent or weak expression of beta-catenin in primary melanomas was associated with several markers of disease progression, including tumour thickness and presence of lymph node metastases. A similar but not statistically significant trend was observed for the association of beta-catenin expression with disease recurrence and prognosis. CONCLUSIONS: These results suggest that loss or downregulation of beta-catenin expression in melanoma cells plays a significant role in progression of the disease.

Adolescent↗

Loricrin keratoderma: a cause of congenital ichthyosiform erythroderma and collodion baby.

A group of hereditary palmoplantar keratodermas due to heterozygous mutation in the loricrin gene has recently been identified. Of five reported pedigrees, four presented as mutilating keratoderma with ichthyosis (variant Vohwinkel syndrome), and one as progressive symmetric erythrokeratoderma. We report a new Japanese pedigree of loricrin keratoderma. A 14-year-old male and his 11-year-old female sibling had both been born as collodion babies and were initially diagnosed as having non-bullous congenital ichthyosiform erythroderma, but later developed palmoplantar keratoderma with pseudoainhum. Their father was similarly affected. Direct sequencing of genomic DNA revealed a G residue insertion at codon 230-231 of the loricrin gene. Antibody studies confirmed the presence of mutant loricrin in the retained nuclei. We conclude that loricrin gene mutation may present as congenital ichthyosiform erythroderma, and should be included in the differential diagnosis of collodion baby.

Adolescent↗

Growth inhibition of human malignant melanoma transfected with the human interferon-beta gene by means of cationic liposomes.

Among the various types of human interferons, human interferon-beta (HuIFNbeta) has the strongest anti-proliferative activity against human melanoma cell lines. Therefore, we investigated the growth inhibitory effect of a cationic liposome containing the HuIFNbeta gene on human melanoma cell lines in vitro and in vivo. After transfection with liposomes containing the HuIFN-beta gene, human melanoma cell lines produced HuIFNbeta in the culture medium at levels ranging from 67 to 3.8 IU/ml on day 6, and growth of the cells was inhibited by 71-92%. Moreover, six injections of liposomes containing the HuIFNbeta gene completely eradicated human melanoma nodules transplanted onto the backs of nude mice 40 days after the first injection. Histological analysis of the injected nodules revealed that the HuIFNbeta gene transfection induced apoptosis of the human melanoma cells. These data suggest that transfection of the HuIFNbeta gene using cationic liposomes is a promising candidate for gene therapy of human melanoma.

Animals↗

Kaposi's varicelliform eruption of an elderly patient with multiple myeloma.

Kaposi's varicelliform eruption (KVE) is characterized by disseminated vesiculopustules and erosions due to a herpes virus infection superimposed on a preexisting dermatosis such as atopic dermatitis. However, the occurrence of KVE in patients with multiple myeloma seems to be very rare; to our knowledge, only one such case has been reported. This report documents a second case of KVE in a patient with multiple myeloma.

Aged↗

Determination of medullasin levels for the diagnosis of multiple sclerosis.

OBJECTIVES: To obtain a simple and reliable clinical parameter for the diagnosis of multiple sclerosis among patients with neurological diseases. PATIENTS AND METHODS: Heparinized peripheral blood was obtained from patients with multiple sclerosis and those with non-inflammatory neurological diseases and healthy volunteers. A new enzyme immunoassay method determining medullasin levels in human granulocytes was developed by using mouse monoclonal antibody against medullasin. RESULTS: A newly developed enzyme immunoassay method for medullasin can detect as little as 1 ng/ml medullasin and results can be obtained within 2 h. Eighty-five out of 112 patients with multiple sclerosis (75.8%) showed positive results (above means of normals + 2 SD) in the medullasin test, while 15.4% (12/78) of patients with non-inflammatory neurological disease had positive results. CONCLUSION: This newly developed enzyme immunoassay method for medullasin is considered to be a useful paraclinical test for the diagnosis of multiple sclerosis.

Adolescent↗

What is the most promising strategy for the treatment of metastasizing melanoma?

The treatment of patients with metastasizing melanoma, still one of the most deadly diseases in modern medicine, ranks among the greatest challenges that a clinician has to face. Metastatic melanoma also is one of the most profound sources of clinical frustration, since it provides far more ultimately defeating experiences than clinical victories. At the same time, the fascinating biology of melanoma has invited the study of this neuroectodermal tumor as a model system for dissecting many of the key problems of modern oncology, ranging from molecular oncogenesis via the controls of tumor proliferation, apoptosis, invasion, metastasis, and angiogenesis to tumor immunosurveillance and tumor drug resistance. Together with the dire need to develop more effective treatment modalities for improving both life expectancy and quality of life of affected patients, this has made metastatic melanoma a favorite model for the exploration of innovative strategies for tumor management. Encouragingly, many of these have already generated very promising results in animal models. However, this impressive level of research progress in conquering melanoma in the animal room contrasts rather pitifully with the actual progress made on the ward. This CONTROVERSIES feature, therefore, critically and soberly reviews the state of the art of treating metastatic melanoma today (distinguishing between nodal and distant metastases), and sharply defines unresolved or comparatively neglected key problems. In addition, this feature highlights several novel, provocative, hitherto underappreciated, yet potentially promising treatment approaches that deserve systematic exploration. Hopefully, this will offer further inspiration for the design and pursuit of innovative anti-melanoma strategies off-the-beaten-track.

Humans↗

Malignant melanoma on the sole: how to detect the early lesions efficiently.

Early detection of malignant melanoma (MM) is essential to improve the prognosis. In non-white populations, including Japanese, the sole is the most prevalent site of MM. On the sole, however, melanocytic nevus is also frequently found. Clinical differentiation of early MM from benign melanocytic nevus on the sole is sometimes difficult because both are observed as a brownish-black macule. For the effective early detection of MM on the sole, the author has proposed guidelines based on the data of hundreds of melanocytic lesions on the sole. The algorithmic guidelines are as follows: when you see a pigmented lesion on the sole, first exclude congenital melanocytic nevus and some other specified disorders, and then measure the maximum diameter of the lesion. If it is more than 7 mm, biopsy it for histopathologic evaluation. If it is 7 mm or less, just follow the course of the lesion and advise the patient to come back if it enlarges to more than 7 mm. Even when the lesion is 7 mm or less, a biopsy is recommended on it, if it shows marked irregularity in shape and/or color or it shows the parallel ridge pattern with epiluminescence microscopy (ELM). The author believes the guidelines surely work efficiently in screening early MM on the sole.

Algorithms↗

Solid facial edema in a patient with rosacea.

We report a 53-year old man with symmetrical nonpitting edema, conjunctivitis, and acneiform eruptions on the face. Histopathological examination showed perifollicular lymphohistiocytic infiltration and telangiectasias in the upper dermis. Loosely aggregated non-caseating granulomas were scattered through the dermis; some of them were seen in the perifollicular regions. The patient was treated with fleroxacin (100 mg/day, orally) for two weeks with a marked reduction of both solid facial edema and periorbital edema.

Anti-Infective Agents↗

Frequency of facial angiofibromas in Japanese patients with multiple endocrine neoplasia type 1.

The high frequency of cutaneous manifestations in patients with multiple endocrine neoplasia type 1 (MEN 1) has recently been reported. Since prevalence of some cutaneous diseases varies among different ethnic groups, we examined the frequency of facial angiofibromas in Japanese patients with familial MEN 1. Among 27 patients with germline MEN1 gene mutation and one asymptomatic gene carrier, angiofibromas were identified in 43% (12/28) of the subjects. This frequency was significantly lower than that of Caucasian patients, but nonetheless almost equaled those of pituitary tumors and pancreas endocrine tumors. Angiofibromas should be considered as one of major manifestations in MEN 1 regardless of patients' ethnic origin, and clinicians should pay careful attention to the cutaneous lesions in patients with endocrine tumors.

Adult↗

The sera from GM1 ganglioside antibody positive patients with Guillain-Barré syndrome or chronic inflammatory demyelinating polyneuropathy blocks Na+ currents in rat single myelinated nerve fibers.

OBJECTIVE: To determine the possible role of anti-GM1 ganglioside antisera from patients with Gullain-Barr*e syndrome (GBS) or chronic inflammatory demyelinating polyneuropathy (CIDP) in the development of nerve dysfunction. METHODS: The effect of the anti-GM1 antibody positive antisera obtained from 4 GBS patients and 1 CIDP patient on membrane potential and ionic currents in rat single myelinated nerve fibers was investigated using the voltage clamp technique and compared with that of the anti-GM1 negative antisera obtained from 3 healthy controls and 2 GBS patients. RESULTS: In the presence of active complement, anti-GM1 positive antisera from 5 patients including 4 GBS patients and 1 CIDP patient significantly suppressed Na+ current more than anti-GM1 negative antisera. CONCLUSION: This study supports the notion that anti-GM1 antibody is one of the causative factors of conduction abnormality in GBS patients.

Adult↗

Sequential chemoimmunotherapy with cisplatin, interferon-beta and interleukin-2 inhibits the growth of B16-F1 melanoma in syngeneic mice.

Sequential combinations of chemotherapy with biological response modifiers has recently been evaluated as systemic treatment for patients with advanced melanoma. The response rates of the chemoimmunotherapy were reported to be higher than conventional treatment using chemotherapy or biological agents alone. To investigate the effectiveness of such chemoimmunotherapy, we evaluated the antitumour effect of sequential chemoimmunotherapy in vivo using a B16 mouse melanoma system. In this sequential regimen, administration of cisplatin (CDDP) was followed by interferon-beta (IFNbeta) and interleukin-2 (IL-2). This combination therapy synergistically inhibited the growth of B16-F1 melanoma and prolonged the survival of mice bearing B16-F1. In contrast, this therapy did not show any antitumour effect on B16-F10 melanoma. The exact mechanism of the antitumour effect is not clear, but the following results were noted: no synergistic effect of this therapy was detected in nude mice, neutralizing anti-IFNgamma antibody significantly blocked the antitumour effect of this therapy, and the number of apoptotic melanoma cells was significantly increased in melanoma tissues removed from mice treated with this therapy. These results demonstrated the potent immunological antitumour effect of this sequential chemoimmunotherapy.

Animals↗

Clinical and analytical evaluation of an enzyme immunoassay for myelin basic protein in cerebrospinal fluid.

BACKGROUND: RIA of myelin basic protein (MBP) in cerebrospinal fluid (CSF) is commonly used as a biochemical marker of demyelination in patients with multiple sclerosis (MS). Our aim was to develop a sufficiently sensitive ELISA for MBP and evaluate it clinically in patients with MS. METHODS: The ELISA used anti-bovine MBP antibody coated on plates and biotinylated anti-MBP antibody. The bound antibody complex was quantified with streptavidin-horseradish peroxidase. MBP was determined in CSF from 84 MS patients and 55 patients with other neurological diseases. RESULTS: The respective within- and between-assay CVs were 4.7% and 7.2% at 200 ng/L, and 6. 3% and 8.8% at 2000 ng/L. The detection limit was 30 ng/L. Most of the MS patients with acute exacerbations had markedly increased MBP in the CSF. Longitudinal studies of six MS patients with recurrent exacerbation confirmed this observation. MBP concentrations from 78 MS patients, as tested with our ELISA, correlated well with those obtained by RIA (r = 0.9; P: <0.01), but the detection limit of the ELISA was much lower than that of the RIA. CONCLUSIONS: This convenient ELISA with higher sensitivity than the existing assays is a suitable routine assay that provides a diagnostic indicator of myelin breakdown in the central nervous system; moreover, it is an excellent indicator of MS disease activity.

Adolescent↗

Increased synthesis of hyaluronate enhances motility of human melanoma cells.

Hyaluronate plays a unique role in the cancer cell microenvironment. In particular, melanoma is the tumor type in which hyaluronate and hyaluronate recognition have been most closely linked to malignancy. In this study we show that a human melanoma cell line stably transfected with hyaluronate synthase cDNA displays enhanced motility. We used a fixed erythrocyte exclusion assay to isolate subsets of the WM793 human melanoma cell line that expressed either high or low amounts of hyaluronate. A cell line with a high level of hyaluronate on its surface (WM793H) displayed significantly higher cell motility on colloidal-gold-coated coverslips than did a line with a low level (WM793L). Next, in order to directly investigate the effects of hyaluronate on melanoma cell migration, we transfected cDNA encoding mouse hyaluronate synthase HAS1 or HAS2 into the re-cloned human melanoma cell line that produced a low amount of hyaluronate (WM793L) by the lipofection method. Several clonal transfectants differentially producing hyaluronate were obtained. There was a positive correlation between total hyaluronate synthesis and formation of the pericellular hyaluronate-rich matrix. We observed an increase in the migration ability of hyaluronate cDNA (HAS1 or HAS2)-transfected cells compared with control cells on glass plates covered with colloidal gold particles. A migration-inhibition assay with anti-CD44 monoclonal antibody showed blocking of the cell motility. It is speculated that the tumor cells might migrate through a hyaluronate-rich extracellular environment when they invade nearby host tissues and that hyaluronate production by the tumor cells could increase this migration. These results suggest that hyaluronate may play a role in the aggressiveness of human melanoma cells.

Animals↗

Long-term open-trial of mizoribine with prednisolone in 24 patients with multiple sclerosis: safety, clinical and magnetic resonance imaging outcome.

OBJECT: Mizoribine (MZR), imidazole nucleotide, inhibits purine synthesis and helper T cell functions. It is used as an immunosuppressant in chronic rheumatic arthritis in Japan. Twenty-four patients with relapsing-remitting and chronic progressive multiple sclerosis (MS) were studied for the long-term effects of MZR over 8 years. METHODS: Average daily MZR doses of 200 mg along with prednisolone (PSL) were administered in the patients studied. Ten of 24 patients were treated for more than 5 years. RESULTS: The mean relapse rate per year at entry (1.50 +/- 0.24, mean +/- SE, n = 22) decreased [0.46 +/- 0.24 (n = 19)] after two years. In 70% of the patients, the disability did not worsen. Eleven of 18 patients showed a mild decrease of the total lesion size in magnetic resonance imaging (MRI). CONCLUSION: MZR was well tolerated and could be used for long-term in MS as an adjunctive immunosuppressant to PSL, and the PSL doses could be decreased. A further randomized controlled trial with PSL is necessary.

Adolescent↗

[The clinical usefulness of high-dose intravenous immunoglobulin therapy for chronic inflammatory demyelinating polyneuropathy and multifocal motor neuropathy].

To explore the optimum dose of intravenous immunoglobulin (i.v.Ig) for treating patients with chronic inflammatory demyelinating polyrneuropathy and multifocal motor neuropathy, we compared the usefulness of i.v.Ig among 3 treatment doses. Fifty-nine patients were randomly divided into three treatment dosage groups: 20 patients for Group I using 50 mg/kg/day x 5 days, 19 patients Group II using 200 mg/kg/day x 5 days, and 20 patients Group III using 400 mg/kg/day x 5 days. We assessed clinically and electrophysiologically the effectiveness of the treatment at 5 weeks after the initial infusion. For patients in Group I and II who had not improved (or worsened) with the first treatment, we gave a one-step larger dose in the second treatment (i.e. 200 mg/kg/day x 5 days for those who had been given 50 mg/kg/day x 5 days, 400 mg/kg/day x 5 days for those who had been given 200 mg/kg/day x 5 days) after more than 9 weeks. We found that 15% of the patients in Group I, 21% in Group II and 60% in Group III improved dose-dependently with the first intravenous immunoglobulin treatment. Seven (47%) of 16 patients in Group I and 4 (40%) of 11 patients in Group II improved after the second treatment with larger doses. Adverse reactions including chill sensation, fever, skin eruption and increase in blood GOT and GPT levels were transient and mild. One patient in Group III developed left hemiparesis showing the small infarction in the right thalamus during the course of the treatment, but the symptom was mild. In conclusion, the high-dose intravenous immunoglobulin therapy (400 mg/kg/day x 5 days) is useful for treating patients with CIDP and MMN, although care must be taken of the risk of causing cerebral infarctions.

Adolescent↗

Anti-GalNAc-GD1a antibody-associated Guillain-Barré syndrome with a predominantly distal weakness without cranial nerve impairment and sensory disturbance.

The serum antibodies to N-acetylgalactosaminyl GD1a (GalNAc-GD1a) and other gangliosides as well as to Campylobacter jejuni were determined in 147 patients with Guillain-Barré syndrome (GBS). We found a distinctive clinical pattern in patients with anti-GalNAc-GD1a antibodies compared with those without the antibodies, that is, lack of cranial nerve involvement (87% versus 38%), distal-dominant weakness (80% versus 25%), and no sensory disturbance (73% versus 22%). The frequency of distal-dominant weakness was significantly higher in patients with both C. jejuni infection and anti-GalNAc-GD1a positivity (100%) than in C. jejuni-negative/anti-GalNAc-GD1a-positive (25%), C. jejuni-positive/anti-GalNAc-GD1a-negative (32%) and C. jejuni-negative/anti-GalNAc-GD1a-negative patients (20%). Lack of cranial nerve involvement and sensory disturbance were found in most C. jejuni-positive/anti-GalNAc-GD1a-positive and C. jejuni-negative/anti-GalNAc-GD1a-positive patients, but not in C. jejuni-positive/anti-GalNAc-GD1a-negative and C. jejuni-negative/anti-GalNAc-GD1a-negative patients. Although the anti-GM1-positive/anti-GalNAc-GD1a-negative patients mostly (75%) lacked cranial nerve involvement, distal-dominant weakness (38%) and lack of sensory disturbance (13%) were infrequent. These results may indicate that (1) the combination of C. jejuni infection and anti-GalNAc-GD1a antibodies, but not anti-GalNAc-GD1a, anti-GM1, or C. jejuni infection alone, is associated with a predominantly distal weakness, (2) the presence of anti-GalNAc-GD1a, rather than C. jejuni infection or anti-GM1 antibody, is associated with a lack of sensory disturbance, (3) both anti-GalNAc-GD1a and anti-GM1 antibodies are independently associated with a lack of cranial nerve impairment.

Acetylgalactosamine↗

[Magnetic resonance imaging in multiple sclerosis].

Useful characteristics of MRI finding of multiple sclerosis (MS) include the distribution of lesions such as a strictly periventricular, infratentorial, or juxtacortical location, involvement of the corpus callosum and the presence of ovoid lesions with long axis directed to lateral ventricles. Our MRI-diagnostic criteria improved the sensitivity and specificity and is clinically useful. New sequences, such as fast spin echo, turbo spin echo or fluid attenuated inversion recovery have improved the detection of lesions. The presence of contrast enhancement in some but not all lesions--that is, evidence of both old and new lesions--provides additional diagnostic support. Enhanced lesions with more than 1 cm diameter often become ring-shaped. Strong correlations were found between the number and volume of enhancing lesions with changes of T 2 and magnetization transfer (MT) lesion loads in patients with secondary progressive MS. The degree of hypointensity of so called black holes on moderately T1-weighted spin echo images correlates with loss of magnetisation transfer, a marker of destruction of matrix and axon, and shows correlation with disability. One of spectroscopic indices of axonal loss is N-acetylaspartate. Atrophy is a process closely linked with the progressive phase of MS and worsening disability. Detection of the reduction in cord cross-sectional area or spinal cord atrophy over time makes an important contribution to the evaluation of therapeutic efficacy, especially in primary progressive disease.

Brain↗