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Biomedical subjects

T Karashima

Publications and source records attributed to T Karashima.

At least 37 records · Page 2Linked to original sources
PubMed1998

Preliminary results of bladder preservation by concurrent intraarterial chemotherapy and radiotherapy for muscle-invasive bladder cancer.

BACKGROUND: We previously reported favorable results of intraarterial doxorubicin chemotherapy in combination with low-dose radiotherapy for locally-advanced bladder cancer. We have now designed a new intraarterial chemotherapy regimen to achieve a higher tumor response rate while preserving a functional bladder. METHODS: Twenty-one patients with muscle-invasive bladder cancer (T2,10; T3,7; T4,4) were treated with concurrent intraarterial chemotherapy and radiotherapy after an initial complete transurethral resection. Induction therapy consisted of concomitant pirarubicin (THP; 15 mg/m2/day on days 1 to 3), cisplatin (CDDP; 25 mg/m2/day on days 8 to 10) and irradiation (2 Gy/session on days 1 to 3 and 8 to 10). Maintenance treatment consisted of THP administered at 20 or 30 mg with or without 50 mg CDDP every month for 2 years. RESULTS: Nineteen of the 21 patients (90.5%) achieved a complete response (CR). One of these 19 relapsed with lung metastases 24 months after treatment and was treated surgically. The 2 patients who did not achieve a CR died of cancer, while the remaining 19 patients are alive with preservation of a functional bladder. CONCLUSION: These findings suggest that a higher tumor response rate with bladder preservation for patients with muscle-invasive bladder cancer is achieved by intraarterial THP/CDDP chemotherapy plus radiotherapy.

Adult↗
PubMed1998

Overexpression of c-Met/hepatocyte growth factor receptors in human prostatic adenocarcinoma.

Hepatocyte growth factor (HGF) and c-met proto-oncogene product (c-Met) have varied biological functions in different tissues and have been implicated in mitogenic, motogenic and morphogenic responses in both organ regeneration and carcinogenesis. Some studies have suggested that the overexpression of c-Met and epidermal growth factor receptor (EGFR) are associated with growth advantage, while transforming growth factor-beta receptor II (TGF beta R II) is associated with growth disadvantage of human prostatic adenocarcinoma. However, it is unclear if the expression of c-Met correlates with the expression of EGFR and TGF beta R II, and with the proliferative status of human prostatic adenocarcinoma. Using immunohistochemical staining with anti-c-Met (C-12), anti-EGFR (NCL-EGFR) and anti-TGF beta R II (L-21) antibodies, we determined the frequency of expression of c-MET, EGFR, and TGF beta R II respectively in a series of 134 radical prostatectomy specimens. We evaluated the relationship between the expression of these receptors and clinicopathological characteristics. Overall, c-Met immunostaining was detected in 54 of 134 (40.3%) cases, EGFR in 45 (33.6%) and TGF beta R II in 64 (48.4%). The overexpression of c-Met was significantly more common in poorly differentiated (P < 0.0001) and in the diffusely infiltrated specimens (P < 0.0005). In contrast, TGF beta R II was significantly overexpressed in the well differentiated specimens (P < 0.0001) and associated negatively with c-Met (P < 0.0001). Overall, these data suggest that c-Met/HGF receptor and TGF beta R II overexpression may be involved in the differentiation of human prostatic adenocarcinoma, c-Met with de-differentiation and TGF beta R II with differentiation.

Adenocarcinoma↗
PubMed1998

[Small cell carcinoma of the prostate: a case report].

A 57-year-old man was admitted with the chief complaint of macrohematuria. Digital rectal examination showed a slightly enlarged, irregular prostate with stony consistency. Serum levels of prostate specific antigen (PSA), neuron-specific enolase (NSE) and progastrin-releasing peptide (ProGRP) were elevated. Transurethral resection (TUR)-biopsy of the prostate revealed small cell carcinoma with poorly differentiated adenocarcinoma. Various radiological examinations revealed metastases to pelvic lymph nodes and liver. He was treated with chemoendocrine therapy consisting of cisplatin, etoposide, flutamide and luleinizing hormone-releasing hormone (LH-RH) agonist. The primary tumor and metastatic lesion decreased and serum PSA, NSE and ProGRP levels were decreased to normal ranges after 5 cycles of chemotherapy. After the 5-cycle chemotherapy, TUR-biopsy proved viable tumor cells. During the additional chemotherapy, tumor markers increased and 4 months later liver metastasis progressed. He died 13 months after diagnosis of small cell carcinoma of the prostate.

Carcinoma, Small Cell↗
PubMed1997

Epidermal cell cultures from involved skin of patients with mammary and extramammary Paget's disease.

In involved epidermis, Paget cells are completely enclosed by the surrounding keratinocytes, which appear to be intact and unaltered. It is possible that the surrounding keratinocytes inhibit Paget cell proliferation. Accordingly, Paget cells might proliferate differently when cultured as an epidermal cell suspension. In this study, primary monolayer cultures of epithelial cells from involved epidermis of patients with mammary and extramammary Paget's disease were carried out to investigate whether Paget cells proliferate in the same manner as other malignant cells. Skin samples were obtained from one patient with mammary Paget's disease, and from 2 patients with extramammary Paget's disease. The epidermis was separated from the dermis with dispase, and epidermal cell suspensions were obtained with ethylenediamine tetraacetate and trypsin. A commercially available serum-free media, Keratinocyte-SFM, was used. Epithelial monolayers from the involved skin could be maintained for approximately 45 days, while keratinocytes from normal skin were maintained for approximately 35 days. The mechanism for the longer survival of the mixed cell culture of keratinocytes and Paget cells is not known. Permanent cell lines were not developed from these primary cultures. Paget cells could not be distinguished from keratinocytes by phase-contrast microscopy. The proportion of carcinoembryonic antigen (CEA) positive cells in the culture did not increase, but instead decreased. In certain areas of the dish, the CEA positive cells proliferated and accumulated like mushrooms. However, at the periphery of the dish, the Paget cells identified by immunostaining for CEA were dispersed and not clustered. These findings indicate that the influence of keratinocytes on Paget cells also occurs in cultured cells, which may explain why Paget cells survive longer than keratinocytes. In conclusion, the Paget cells in the involved epidermis do not proliferate like other malignant cells.

Aged↗
PubMed1997

Expression of desmogleins in Paget cells of mammary and extramammary Paget's disease.

Sagebiel (1969) electronmicroscopically observed that desmosomes are present between adjacent Paget cells, as well as between Paget cells and adjacent keratinizing epidermal cells. Desmosomes contain the proteins desmoglein (Dsg) and desmocollin as their transmembrane components, and Dsg has three isotypes. Among the three isotypes of Dsg, Dsg1 and Dsg3 are autoantigens for pemphigus foliaceus and pemphigus vulgaris (PV), respectively. We examined the expression of Dsgs in Paget cells of mammary and extramammary Paget's disease. Skin samples were obtained from one patient with mammary Paget's disease, and from 2 with extramammary Paget's disease. One part of the samples was cut into small pieces and epidermal sheets were separated with dispase, then treated with a mixture of EDTA and trypsin. The resulting cell suspensions were cultured in low Ca++ medium, then the cells were incubated in high Ca++ medium. Paget cells identified with anti-epithelial membrane antigen (EMA) antibody were positive for serum from a PV patient which was confirmed to react with both Dsg1 and Dsg3. However, the intensity of fluorescence of Paget cells was weaker than that of EMA-negative keratinocytes. In the cryostat sections, Paget cells identified with anti-EMA antibody showed the same staining pattern as cultured cells in high Ca++ medium. The data presented in this study confirm that Paget cells express Dsgs, and are consistent with the electronmicroscopical data by Sagebiel (1969). However, our data do not support the hypothesis that Paget cells are of keratinocyte origin, because sweat ducts or sweat glands could be positive for sera from PV patients. It is necessary to confirm whether or not sweat ducts or sweat glands express Dsgs, because sera from PV patients exhibit high background in the dermis.

Aged↗
PubMed1997

[Usefulness of recombinant human erythropoietin on predeposit autologous blood transfusion in patients undergoing radical prostatectomy].

The usefulness of recombinant human erythropoietin (rHuEPO) on autologous blood transfusion was investigated in 18 patients undergoing radical prostatectomy (mean age 67.4 years). A total of 800 ml blood was deposited by two donations of 400 ml each, concomitant with subcutaneous administration of 24,000 U rHuEPO at each donation. All patients completed two successive donations with no adverse effects. The mean hemoglobin concentration was 13.7 g/dl before the donation and 13.0 g/dl on the day of operation. The decrease in hemoglobin was effectively prevented in 12 patients (66.7%) with rHuEPO, when compared with the predicted decrease in the absence of recovery from anemia. During radical prostatectomy, no homologous blood transfusion was required in 16 of 18 patients (88.9%). In conclusion, predeposit autologous blood transfusion with rHuEPO is useful for diminishing the risks associated with homologous blood transfusions.

Aged↗
PubMed1996

FK506 and cyclosporin A inhibit growth factor-stimulated human keratinocyte proliferation by blocking cells in the G0/G1 phases of the cell cycle.

FK506, a new immunosuppressive agent, is effective in treating patients with psoriasis. A major feature of psoriasis vulgaris is the hyperproliferation of keratinocytes together with inflammation. To determine the effect of FK506 or cyclosporin A (CsA) on the keratinocyte cell cycle, flow cytometry and the growth factor free normal human keratinocyte-arrested system were used to assess keratinocyte proliferation. FK506 and CsA inhibit keratinocyte proliferation induced by EGF, TGF-alpha or IL-6. The antiproliferative effects of FK506 and CsA directly correlated with blockade of the keratinocyte cell cycle at the G0/G1 phases. These findings might indicate that the effects of FK506 and CsA on proliferation of cultured normal human keratinocytes are probably related to direct effects on growth regulation of keratinocytes via EGF, TGF-alpha or IL-6 stimulation.

Cell Division↗
PubMed1996

[Glutathione chemoprotection therapy against CDDP-induced neurotoxicity in patients with invasive bladder cancer].

We studied the efficacy of glutathione in the prevention of CDDP-induced neurotoxicity. Nine patients with muscle-invasive bladder cancer were treated with intra-arterial THP and CDDP chemotherapy plus radiotherapy. Glutathione was given at a dose of 1,500 mg/m2 before CDDP administration and at a dose of 600 mg/body on days 2 to 4. The CR rate of 9 patients was 89%, and 2 of the 9 patients developed grade 1 neurotoxicity. These patients were then compared with 15 patients treated with the same regiment but without glutathione. The two groups did not differ in CR rate (89% vs 87%), but the incidence of neurotoxicity of patients with glutathione was significantly lower than that of patients without glutathione (22% vs 73%).

Adult↗
PubMed1996

Serum from normal elderly individuals contains anti-basement membrane zone antibodies.

BACKGROUND: Bullous pemphigoid is an autoimmune bullous disease with circulating anti-basement membrane zone antibodies, and it commonly affects elderly individuals; however, the reasons for the late onset of the disease are unclear. DESIGN: The anti-basement membrane zone antibodies in serum samples from normal elderly subjects were compared with those in serum samples from normal young subjects. PARTICIPANTS: Serum samples from 32 elderly and 28 young normal individuals and 10 patients with bullous pemphigoid were used. INTERVENTIONS: Indirect immunofluorescence against guinea pig esophagus or human salt-split epidermis and immunoblotting against human and guinea pig epidermis were performed. RESULTS: Serum samples from young individuals were devoid of anti-basement membrane zone antibodies against guinea pig esophagus and human salt-split epidermis. Among 32 serum samples from elderly patients, 6 cases (19%) were positive for anti-basement membrane zone antibody for guinea pig esophagus, and in those the titers were 10 in 3 cases and 40, 80, and 320 in the others. One case was positive against human split epidermis at a titer of 10. An immunoblotting analysis showed that the antigenicity of the 230-kd and 180-kd bullous pemphigoid antigen from guinea pig epidermal extract was similar to that of human epidermal extract; however, the molecular weight was slightly different. The 4 cases of elderly serum that recognized guinea pig esophagus basement membrane zone showed positivity with the 230-kd peptide in the guinea pig epidermal extract; however, they were negative with the human epidermal extracts. Direct immunofluorescence observation of these cases showed that deposition of IgG or C3 was not present in cryostat sections from flexor arm surfaces. CONCLUSIONS: The serum samples from elderly subjects possessed a relatively high incidence of anti-basement membrane zone antibodies detectable with guinea pig esophagus as substrate. This observation of a specific immune defect in elderly individuals might explain why they are more susceptible to developing bullous pemphigoid.

Adult↗
PubMed1995

Keratin 14 gene point mutation in the Köbner and Dowling-Meara types of epidermolysis bullosa simplex as detected by the PASA method.

Recent advances in molecular biology have enabled the association of epidermolysis bullosa simplex (EBS) with point mutations of keratin 14 and/or keratin 5 genes to be established. We describe here the detection of point mutations in genomic DNA from formalin-fixed and paraffin-embedded sections from five cases of epidermolysis bullosa using the PCR amplification of specific alleles (PASA) method. In two of four cases of Köbner-type EBS a point mutation of helix 2b (384 Leu-Pro) was detected and in one case of Dowling-Meara-type EBS a mutation in helix 1a (125 Arg-Cys) was detected. The results of this study are consistent with previous reports and they demonstrate that the PASA method is a rapid and reproducible method for the detection of single-base changes and small deletions.

Alleles↗
PubMed1993

Toxic pustuloderma induced by ofloxacin.

A patient with drug-induced toxic pustuloderma is presented. The patient, who was asthmatic and who was being treated with ofloxacin for bronchitis and pharyngitis, developed intense erythemas followed by subcorneal pustulation associated with fever and a neutrophil leukocytosis. The diagnosis was confirmed by oral readministration of ofloxacin, with the result that pustular eruptions were induced. This form of drug eruption had not previously been attributed to ofloxacin.

Bronchitis↗
PubMed1992

Epidermal keratinocytes of bullous pemphigoid express intercellular adhesion molecule-1 (ICAM-1).

Intercellular adhesion molecule-1 (ICAM-1) is the ligand for lymphocyte function associated antigen-1 (LFA-1), mediating the adhesion of lymphocytes to vascular endothelium. Keratinocytes are known to express ICAM-1 in some inflammatory dermatoses. Using an indirect immunofluorescence method, we examined the patterns of ICAM-1 and LFA-1 staining in bullous pemphigoid (BP) lesions and compared them to pemphigus vulgaris (PV) cases. ICAM-1 was expressed on the cell surface and in the cytoplasm of epidermal keratinocytes at the sites of erythematous and bullous lesions of BP. LFA-1 molecules were expressed on T cells at the basement membrane zone. In addition, HLA-DR-positive keratinocytes were observed in the basal layer. ICAM-1 was not, however, expressed on epidermal keratinocytes in uninvolved skin from BP patients, PV or normal control skin. It is known that ICAM-1 is expressed on keratinocytes at the site of lymphoid infiltration in cutaneous dermatoses and that LFA-1-positive T cells can bind to interferon gamma-induced ICAM-1-positive keratinocytes. Our results suggest that cellular immunity involving ICAM-1 and LFA-1 may play a part in the pathogenesis of bullous pemphigoid.

Cell Adhesion↗
PubMed1992

Surface charge of fractionated guinea pig keratinocytes measured by free-flow cell electrophoresis.

Keratinocytes differentiate from basal cells to spinous, granular, and horny layer cells. It is known that alterations in the surface charge of cell membranes in most cases reflect the processes of differentiation. By using a continuous colloidal silica (Percoll) density gradient, keratinocytes may be separated into three fractions which correspond to their arrangement in vivo. Using a free-flow cell electrophoretic technique, we measured the electrophoretic mobility of guinea pig keratinocytes. Electrophoretic mobility histograms of basal and granular cells showed slow and fast monophasic patterns, respectively. In spinous cells, a biphasic pattern of slow and fast electrophoretic mobility was present. The electrophoretic mobility level of guinea pig keratinocytes was slightly reduced with neuraminidase digestion. Those of human red blood cells and lymphocytes, however, were markedly decreased. These results indicate that membrane charge density is lower in basal cells and higher in granular cells and that the membrane charge density of guinea pig keratinocytes involves not only neuraminic acid residues but also other substance(s). Our results illustrate the alterations of cell membrane charge properties during epidermal cell differentiation.

Animals↗
PubMed1991

Bullous pemphigoid antigen expression in Pam 212 cells induced by the addition of platelet activating factor.

Platelet activating factor (Paf-acether) is a phospholipid which has various activities including platelet and neutrophil aggregation and eosinophil chemotaxis. We have previously reported that the blister fluids of bullous pemphigoid possess platelet aggregation activity and suggested that Paf-acether might be concerned with the accumulation and activation of neutrophils and eosinophils. In this study, we examined the influence of Paf-acether on BP antigen expression on Pam 212 cells. Paf-acether enhanced the expression of BP antigen on Pam 212 cells and this expression was blocked by Paf-acether antagonist. Our observations might suggest that Paf-acether contributes to the blister formation not only by the activation of inflammatory cells but the enhancement of BP antigen.

Animals↗
PubMed1991

Monoclonal antibody KOLT-2 enhances DNA synthesis and expression of IL-2 receptors on activated T cells.

The functional properties of the KOLT-2 antigen, which was placed among the CD28 group in the 3rd International Workshop on Human Leukocyte Differentiation Antigens, are described. The method of production and a detailed characterization of the monoclonal antibody KOLT-2 including stain affinities and influence of T cell activation are presented. While KOLT-2 antigen was selectively expressed on human thymocytes, adult T-cell leukemia-lymphoma cells and activated T cells, the antigen was also spontaneously expressed by resting T cells after 24 hrs culture. Expression was transient, since it disappeared after 96 hrs. DNA synthesis and expression of Tac antigen on activated T cells was enhanced by stimulation with the KOLT-2. These observations suggest that the KOLT-2 antigen may have an important role in the early stages of T cell activation.

Antibodies, Monoclonal↗
PubMed1991

Low concentrations of interferon-gamma stimulate DNA synthesis in normal human keratinocytes during the initial stages of cultivation.

High concentrations of interferons can inhibit keratinocyte proliferation and induce the expression of HLA-DR antigen on keratinocytes. In the present study, the effects of low concentrations of recombinant human interferon alpha, beta and gamma were examined on DNA synthesis and the expression of HLA-DR and bullous pemphigoid (BP) antigens in normal human keratinocytes. Low concentrations of interferons induced DNA synthesis in normal human keratinocytes when epidermal cell growth factor and low Ca++ were used during the initial stages of culturing. This result indicates that physiological concentrations of interferons can induce keratinocyte activation.

Animals↗
PubMed1991

[A case report of idiopathic myxedema with secondary amenorrhoea and hyperprolactinemia: effect of thyroid hormone replacement on reduction of pituitary enlargement and restoration of fertility].

A 37-year old housewife was admitted to our department because of long-standing amenorrhoea and galactorrhoea. After several hormonal examinations, she was proved to be suffered from primary hypothyroidism with hyperprolactinemia. In addition, brain computed tomography (CT) showed the finding of enhanced pituitary enlargement, suggesting pituitary hypertrophy or pituitary adenoma. Based on some therapeutic experiences in similar cases in several reports, we have performed only thyroid hormone replacement and followed up the patient. Plasma thyroid stimulating hormone (TSH) and prolactin concentrations returned to normal range in a few months after starting thyroid hormone replacement. Furthermore, the finding of pituitary enlargement has completely disappeared on brain CT and come to pregnancy during the course. Thus, it seems that the finding of pituitary enlargement might be due to pituitary hypertrophy. Therefore, we think that thyroid hormone replacement should be a first choice therapy preceding the pituitary surgery or bromocriptine therapy in such a case.

Adult↗