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M Kanda

Publications and source records attributed to M Kanda.

At least 19 recordsLinked to original sources
PubMed2000

Inhibitory effects of PGD2, PGJ2 and 15-deoxy-delta12,14-PGJ2 on iNOS induction in rat mesenteric artery.

PGD2 and its metabolites PGJ2 and 15-deoxy-delta12,14-PGJ2 have been reported to inhibit iNOS induction in cultured vascular smooth muscle cells. The present study was undertaken to determine whether these prostanoids inhibit iNOS induction in the isolated rat mesenteric artery. The artery without endothelium was incubated with and without lipopolysaccharide (LPS) at 37 degrees C for 6 hrs, then washed and mounted in an organ bath to measure isometric changes in tension. L-arginine but not D-arginine (10(-6) - 10(-3) M) induced concentration-dependent relaxations only in the artery preincubated with LPS, the relaxations of which were attenuated by L-N(G)-nitroarginine methyl ester (LNAME, 10(-4) M), a non-selective iNOS inhibitor, and 1400W (10(-5) and 10(-4) M), a selective iNOS inhibitor. Co-treatment of cycloheximide (10(-5) M), a protein synthesis inhibitor, or actinomycin D (10(-7) M), an RNA synthesis inhibitor with LPS inhibited the development of relaxing ability in response to L-arginine, indicating iNOS induction by LPS. PGD2, PGJ2 and 15-deoxy-delta12,14-PGJ2 but not PGE2, PGI2 or PGF2alpha also inhibited the development of relaxing ability in response to L-arginine when added during incubation with LPS. Incubation of the artery with LPS at 37 degrees C for 6 hrs markedly increased production of nitric oxide (NO), which was abolished by 15-deoxy-delta12,14-PGJ2 (10(-5) M). An imunohistochemical study using antibody against murine iNOS showed that 15-deoxy-delta12,14-PGJ2 (10(-5) M) inhibited the expression of iNOS protein in isolated rat mesenteric arteries. These results demonstrated that PGD2 and its metabolites inhibit iNOS induction by LPS in isolated rat mesenteric arteries, resulting in reduced relaxing ability in response to L-arginine.

Animals↗
PubMed2000

Primary somatosensory cortex is actively involved in pain processing in human.

We recorded somatosensory evoked magnetic fields (SEFs) by a whole head magnetometer to elucidate cortical receptive areas involved in pain processing, focusing on the primary somatosensory cortex (SI), following painful CO(2) laser stimulation of the dorsum of the left hand in 12 healthy human subjects. In seven subjects, three spatially segregated cortical areas (contralateral SI and bilateral second (SII) somatosensory cortices) were simultaneously activated at around 210 ms after the stimulus, suggesting parallel processing of pain information in SI and SII. Equivalent current dipole (ECD) in SI pointed anteriorly in three subjects whereas posteriorly in the remaining four. We also recorded SEFs following electric stimulation of the left median nerve at wrist in three subjects. ECD of CO(2) laser stimulation was located medial-superior to that of electric stimulation in all three subjects. In addition, by direct recording of somatosensory evoked potentials (SEPs) from peri-Rolandic cortex by subdural electrodes in an epilepsy patient, we identified a response to the laser stimulation over the contralateral SI with the peak latency of 220 ms. Its distribution was similar to, but slightly wider than, that of P25 of electric SEPs. Taken together, it is postulated that the pain impulse is received in the crown of the postcentral gyrus in human.

Adult↗
PubMed2000

Endothelium-dependent relaxation followed by contraction mediated by NK(1) receptors in precontracted rabbit intrapulmonary arteries.

In the present study, we examined whether substance P (SP) and SP methyl ester (SPME), a selective NK(1) agonist, cause biphasic responses consisting of endothelium-dependent relaxation (EDR) and contraction (EDC) in precontracted rabbit intrapulmonary arteries. In arteries contracted with PGF(2alpha) (2x10(-6) M), SP as well as SPME caused only EDR at low concentration (10(-9) M) and EDR followed by EDC at higher concentrations, indicating the involvement of NK(1) receptors. The SP (10(-8) M)-induced EDR was abolished in arteries moderately contracted by PGF(2alpha) (5x10(-7) M) and the EDC in arteries maximally contracted by PGF(2alpha) (10(-5) M), indicating that EDR and EDC are inversely dependent on preexisting tone. Indomethacin (10(-8) - 10(-6) M), a cyclo-oxygenase inhibitor, and ozagrel (10(-8) - 10(-6) M), a TXA(2) synthetase inhibitor attenuated the EDC in the SPME (10(-7) M)-induced biphasic response and markedly potentiated the EDR. AA-861 (10(-8) - 10(-6) M), a 5-lipoxygenase inhibitor, did not affect the EDR or EDC. L-N(G)-nitro-arginine methyl ester (10(-5) - 10(-4) M), a nitric oxide synthase inhibitor, attenuated the EDR and slightly potentiated the EDC. CP-99994 (10(-10) - 10(-8) M), an NK(1) antagonist, attenuated the EDC and potentiated the EDR in the SPME (10(-7) M)-induced biphasic response, while the NK(2) antagonist SR-48968 (10(-9) - 10(-7) M) had no effect. CP-99994 attenuated the SPME (10(-7) M)-induced EDC under EDR-blockade to a greater extent than the EDR under EDC-blockade, indicating that CP-99994 enhanced the EDR component by preferential inhibition of the EDC component. In conclusion, NK(1) agonists caused a biphasic endothelium-dependent response (EDR and EDC) in submaximally precontracted intrapulmonary arteries. The EDC and EDR mediated by NK(1) receptors may play physiological and/or pathophysiological roles in modulation of vascular tone.

Animals↗
PubMed2000

Epstein-Barr virus-associated lymphoproliferative disease after a cord blood transplant for Diamond-Blackfan anemia.

A 7-year-old boy with Diamond-Blackfan anemia (DBA) developed lymphoproliferative disease (LPD) after a cord blood transplant (CBT). 3.1 x 107/kg mononuclear cells from an HLA one-locus mismatched CB were transplanted after conditioning with total body irradiation (8 Gy), cyclophosphamide (200 mg/kg) and antithymocyte globulin (10 mg/kg). Complete engraftment occurred on day 33 post transplant. Despite the resolution of grade II graft-versus-host disease (GVHD), he died of lymphoma on day 130 post transplant. The tumor was of donor origin, indicating clonal proliferation of Epstein-Barr virus (EBV)-infected B cells. This is the first report of EBV-LPD after CBT. Post-transplant LPD can be a serious EBV-associated complication of CB grafts. Bone Marrow Transplantation (2000) 25, 209-212.

Blood Component Transfusion↗
PubMed2000

Hepatosplenic gammadelta T-cell lymphoma: relation to Epstein-Barr virus and activated cytotoxic molecules.

AIMS: Hepatosplenic gammadelta T-cell lymphoma (TCL) is a rare, aggressive subset of peripheral TCL that presents with hepatosplenomegaly and cytopenia. Epstein-Barr virus (EBV) infection and activated cytotoxic molecules (granzyme and perforin) are uncommon in hepatosplenic gammadelta CTL. EBV infection and activated cytotoxic molecules are occasionally detected in non-hepatosplenic gammadelta TCL. We describe the clinicopathological features of three Japanese cases who were not immunodeficient. METHODS AND RESULTS: All cases showed gammadelta T-cell type (CD2+, CD3+, T-cell receptor (TCR)delta-1+, betaF1-). Two cases expressed natural killer (NK) cell-associated antigens (CD8-, CD16+, CD56+; CD8-, CD16-, CD56+), and one expressed CD8 (CD8+, CD16-, CD56-). All cases expressed cytotoxicity-associated molecules (perforin, granzyme B, TIA-1 and Fas ligand). However, perforin and Fas ligand were not detected in one case. In-situ hybridization analysis with EBER probes revealed strong nuclear positivity in all neoplastic cells. In addition, two cases showed clonal bands of the EBV terminal repeat (TR) gene. Cytologically, instead of the presence of monomorphic medium-sized cells, our three cases showed pleomorphic medium-sized and large cells. CONCLUSIONS: Our gammadelta TCL cases were clinicopathologically considered to be compatible with hepatosplenic gammadelta T-cell lymphoma. However, with regard to EBV association, activated cytotoxic profile and cytological features they resembled non-hepatosplenic gammadelta TCL. EBV may play a role in this disease by inducing cellular activation.

Adult↗
PubMed2000

Effect of HIV-1 infection on tuberculosis and fertility in a large workforce in Kinshasa, Democratic Republic of the Congo.

To determine the effect of an HIV counseling service on the incidence of HIV and tuberculosis infection and on the fertility rate in a large workforce cohort of adult men and women from Kinshasa, Democratic Republic of Congo (formerly Zaire), we conducted a 2-year prospective longitudinal cohort study, two large Kinshasa businesses (a commercial bank and a textile factory). We determined baseline HIV-1 seroprevalence, HIV-1 and tuberculosis mortality/morbidity, and fertility rates during 24 months of follow-up on 8866 employees and 6411 wives of male employees. The baseline HIV-1 seroprevalence was 2.8% in male employees (n = 6657), 8.4% in female employees (n = 417), and 2.4% in the wives of male employees (n = 4692). The HIV-1 seroincidence per 100 person-years of follow-up in these three groups was 0.9, 0.5 and 0.8, respectively. The incidence of tuberculosis was 2.4/100 person years in persistently seropositive individuals compared with a 0.38 rate in persistently seronegative individuals (p < 0.01). The annual fertility rate in persistently seronegative women was 250.0/1000 women compared with a rate of 140/1000 in persistently seropositive women (p < 0.001). Forty-eight (44%) of 105 male employees and 17 (26%) of 60 wives of male workers who died during follow-up were HIV-1 seropositive. HIV infection was responsible for nearly one half of all deaths in this large workforce. Tuberculosis incidence was six times higher in HIV-1-infected compared with uninfected individuals. Counseling of HIV-infected women and their husbands appeared to be effective as their cumulative fertility rate was 44% lower than the rate in similarly aged uninfected women.

AIDS-Related Opportunistic Infections↗
PubMed2000

Bioavailable acyl-CoA: cholesterol acyltransferase inhibitor with anti-peroxidative activity: synthesis and biological activity of novel indolinyl amide and urea derivatives.

We synthesized a series of indoline derivatives with an amide or urea moiety and examined their inhibitory effects on acyl-CoA:cholesterol acyltransferase (ACAT) activity, lipid-peroxidation and serum cholesterol levels in experimental animals. Among the derivatives synthesized, a series of N-(1-alkyl-4,6-dimethylindolin-7-yl)-2,2-dimethylpropanamides++ + potently inhibited rabbit intestinal ACAT activity and lipid-peroxidation of rat brain homogenate. The effect on ACAT activity was related to the length of the alkyl chain at the 1-position of indoline. N-(4,6-Dimethyl-1-octylindolindolin-7-yl)-2,2-dimethylpropanami de hydrochloride (55) showed inhibitory effects on intestinal and hepatic ACAT activity slightly weaker than those of YM-750, and an inhibitory effect on low density lipoprotein (LDL)-peroxidation similar to that of probucol. Compound 55 also reduced serum cholesterol at 10 mg/kg/d in hyperlipidemic rats and 20 mg/kg/d in normolipidemic hamsters. The plasma concentration of 55 reached 716 ng/ml in dogs (10 mg/kg, p.o.), which is an effective concentration against hepatic ACAT activity and LDL-peroxidation. In conclusion, compound 55 is a novel bioavailable ACAT inhibitor with anti-peroxidative activity and is thus a promising anti-atherosclerotic and anti-hyperlipidemic drug. Indoline proved to be a useful pharmacophore for molecular design of new anti-peroxidative drugs.

Amines↗
PubMed2000

A case of multiple myeloma which developed into multiple extramedullary involvement in the terminal stage.

A 69-year-old man with a diagnosis of multiple IgG class myeloma received combination chemotherapy. He achieved a partial response with an undetected M spike. However, he demonstrated new lytic bone lesions and multiple extramedullary involvement 10 months after the initial presentation. Polymerase chain reaction (PCR) analysis using a framework 3 (Fr3) V-region primer clarified a discrete band in the extramedullary tumor, while it yielded 4 bands including the same size as the extramedullary tumor produced in the bone marrow sample obtained before the chemotherapy. These findings suggest that a resistant and non-secretory clone was selected by the combination chemotherapy.

Aged↗
PubMed1999

Primary chemically induced tumors induce profound immunosuppression concomitant with apoptosis and alterations in signal transduction in T cells and NK cells.

Whereas transplantable tumors can be readily cured with immunotherapeutic approaches, similar therapies in cancer patients have been less effective. This difference may be explained by an immunosuppression resulting from the presence of a slowly growing primary tumor in the patient, whereas the immune system in a mouse with a rapidly proliferating transplantable tumor would be less affected. As a more appropriate model to the immune dysfunction in patients, slowly progressing primary tumors were induced by the carcinogen methylcholanthrene (MC) in mice. Their ability to induce immunosuppression in T cells and natural killer (NK) cells was compared to that of rapidly growing transplanted MC-induced tumors. The results demonstrate that mice bearing primary MC tumors had significantly diminished T-cell and NK-cell functions, impaired capacity to produce Th1 cytokines, and markedly reduced levels of the signal-transducing zeta chain in T cells and NK cells, similar to that described in cancer patients. Moreover, a substantial number of CD8+ T cells in mice with large primary MC tumors were undergoing apoptosis, correlating with alterations in CD4/CD8 ratios. In contrast, T cells and NK cells from mice bearing rapidly growing transplanted tumors were only marginally affected. These findings could explain the apparent discrepancy between the consistent findings of a diminished immune response and alterations in signal transduction in cancer patients as compared to the less reproducible observations in murine transplantable tumors. In addition, they could explain the differences in the high efficacy of immunotherapy in mice with transplantable tumors and the low therapeutic results in cancer patients.

Animals↗
PubMed1999

Antibody reactivity in mice and cats to feline enteroepithelial stages of Toxoplasma gondii.

The reactivity of antibodies in mice and cats to feline enteroepithelial stages of Toxoplasma gondii was examined by means of an indirect immunofluorescent antibody test. Mice immunized with feline enteroepithelial stage (FES) parasites produced antibodies not only against FES, but also against tachyzoites, sporozoites/oocysts, tissue cysts and one part of the infected feline enterocytes. After absorption with tachyzoites, the titer of antibodies reactive to enterocytes was significantly reduced. In contrast, the titer of antibodies reactive to FES remained unchanged. The antibodies from cats immunized with FES, reacted specifically to FES, but not to tachyzoites, tissue cysts or enterocytes. These results suggest that FES parasites may have stage-specific antigen(s).

Animals↗
PubMed1999

B-cell lymphoma of 708 cases in Japan: incidence rates and clinical prognosis according to the REAL classification.

New insights into the pathogenesis of lymphoid malignancies have been gained through novel techniques such as genetic, molecular and immunologic methods. Recently, based on those findings, a new classification system for lymphoid malignancies, known as the REAL classification, has been proposed. To clarify the relation between the histological classification and prognosis of B-cell lymphoid malignancies, we re-classified 708 cases. In all cases, the B-cell phenotype and/or genotype was confirmed by immunohistochemical staining and/or receptor gene analysis. The most common B-cell lymphoma types were diffuse large B-cell lymphoma (58.8%), follicular lymphoma (12.1%), marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT) (9.0%) and mantle cell lymphoma (5.9%). Minor types were lymphoblastic lymphoma (3.4%), Burkitt's lymphoma (2.4%), nodal marginal zone lymphoma (2.1%), lymphoplasmacytic lymphoma (2.0%) and plasmacytoma (1.4%). Rare types were prolymphocytic lymphoma and splenic marginal zone lymphoma. Using overall survival rates, the various B-cell lymphoma types could be divided into three broad groups for prognostic purposes: (1) the low risk group consisted of follicular lymphoma, marginal zone lymphoma of MALT, nodal marginal zone lymphoma, plasmacytoma and lymphoplasmacytic lymphoma; (2) the intermediate risk group consisted of diffuse large B-cell lymphoma, Burkitt's lymphoma and mantle cell lymphoma; and (3) the high risk group consisted of lymphoblastic lymphoma. In MALT, the low grade type had a better prognosis than the high grade type. In diffuse large B-cell lymphoma, the common type had a better prognosis than the variant type, which mainly consisted of the immunoblastic lymphoma. The histological classification will have a benefit for the clinical approach.

Adolescent↗
PubMed1999

Survival of patients with HTLV-I-associated lymph node lesions.

Adult T-cell leukaemia/lymphoma (ATLL), is a malignant condition associated with human T-cell leukaemia virus type I (HTLV-I). Usually, although not uniformly, histopathological examination of the lymph nodes shows a pleomorphic type. In addition, some patients with pre-overt ATLL show a Hodgkin's disease-like morphology and lymph nodes in non-neoplastic carriers show features of lymphadenitis. To characterize further the clinicopathological features of HTLV-I-associated lymphadenopathy, the histopathological features of the lymph nodes of 289 patients were classified into five types: lymphadenitis ( n=14), Hodgkin's-like (Hodgkin's) ( n=18), pleomorphic (medium and large cells) ( n=219), pleomorphic small cell ( n=11), and anaplastic large cell (ALC) ( n=27). Survival data were analysed according to the histopathological features of the lymph nodes. The pleomorphic type, which showed typical features of ATLL, was associated with a highly aggressive course and an initially high mortality, followed by a rapid decrease in survival. This pattern was also observed in patients with the ALC type. All cases with lymphadenitis were still alive at the end of the study, while survival progressively decreased in the Hodgkin's type. The small cell type showed an initial rapid decrease in survival followed by a plateau. These results show that the survival trends of patients with pleomorphic and anaplastic lymph node lesions are similar to those with ATL lymphoma, while patients with the lymphadenitis type of lesion were considered to have a non-neoplatic status. There is at present no effective therapy for ATLL, but in the future, these classification and survival data might be useful for the selection of appropriate chemotherapeutic regimens for patients with ATLL.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1999

Cortical mechanisms underlying point localization of pain spot as studied by event-related potentials following CO2 laser stimulation in man.

To elucidate cortical mechanisms underlying point localization of a pain spot, we investigated event-related potentials (ERPs) while using a CO2 laser beam to apply a pain stimulus to the hand dorsum in 16 healthy men. The stimulus spot (pain spot) was shifted for each stimulus, while the subject was requested to identify the stimulated spot as accurately as possible and to use a pointer in the non-stimulated hand to indicate the corresponding spot on a figure of a hand that was projected onto a screen (localization condition). For the control condition, the subject pointed to a single predetermined spot, regardless of the location of the stimulation (control motor task condition). Electroencephalograms were recorded from 21 electrodes, referenced to the linked earlobes, and were averaged time-locked to the stimulus onset for each task separately. Under the control rest condition (neither point localization nor motor task), only two early components (N2 and P2) were recorded. During the control motor task condition (no point localization), in addition to N2 and P2, a steep negative-going slope was recorded at the fronto-central region. Exclusively during the localization condition, a positive peak (647 ms, 5.6 microV for the left and 634 ms, 5.7 microV for the right hand stimulation) was identified; this was maximal at the midline centro-parietal area and distributed symmetrically over the scalp. It is suggested that the late positive component detected exclusively during the localization task is related to the somatotopic point localization of the pain spot. From the distribution of this ERP, the task most likely involves bilateral activation of the superior parietal cortices.

Adult↗
PubMed1999

Clinical, immunohistochemical and phenotypic features of aggressive nodal cytotoxic lymphomas, including alpha/beta, gamma/delta T-cell and natural killer cell types.

Cytotoxic cells include natural killer (NK) cells and cytotoxic alpha beta and gamma delta T lymphocytes (CTLs). These cells express cytotoxic molecules of T-cell restricted intracellular antigen (TIA-1), and activated cytotoxic molecules of perforin, granzyme B, and FasL. Recent studies suggest that most extranodal T-cell lymphomas are derived from CTLs, and that NK cell lymphomas are extranodal. However, only a few nodal NK and cytotoxic lymphomas have been described so far. We present here the clinicopathological features of seven cases of nodal cytotoxic T and NK cell lymphomas. The study excluded anaplastic large-cell lymphomas expressing cytotoxic molecules. The neoplastic cells of all cases contained activated cytotoxic molecules of TIA-1, granzyme B, Fas ligand, and/or perforin. Phenotypically and genotypically, four cases showed alpha beta T cell type [CD2+, CD3+, T-cell receptor (TCR)-delta-1-, beta F1+, and TCR gene rearrangement], two cases showed gamma delta cell type [CD2+, CD3+, T-cell receptor (TCR) delta-1+, beta F1-, and TCR gene rearrangement], and one case showed NK cell type [CD2+, CD3-, CD56+, T-cell receptor (TCR) delta-1-, beta F1-, and TCR gene germline]. Using Southern blot analysis, Epstein-Barr virus (EBV) sequences were detected in six cases, and monoclonal terminal repeat proliferation was confirmed. In addition, in situ hybridization (ISH) studies for EBV showed EBV infection in almost all neoplastic cells. Clinically, all patients presented with peripheral lymphadenopathy in high clinical stages and showed an aggressive course. Hepatosplenomegaly was detected in six cases. During the course of the disease, bone marrow and extranodal invasion were noted in five cases. The nodal type showed an aggressive clinical course in all cases but one, as did the extranodal type. The nodal type varied in phenotype, but was closely associated with EBV infection.

Adolescent↗
PubMed1999

Absence of cytotoxic molecules in CD8- and/or CD56-positive adult T-cell leukaemia/lymphoma.

Adult T-cell leukaemia/lymphoma (ATLL) cells usually exhibit a CD4+ (helper/inducer) phenotype (CD4+/8-/56-), and only a minority of tumours express the CD8 (cytotoxic/suppressor) or CD56 (natural killer [NK]-associated) antigens. TIA-1 is a cytotoxic granule-associated protein expressed in NK cells and cytotoxic T lymphocytes (CTLs). Granzyme B, perforin and Fas ligand (FasL) are also expressed in activated CTLs and NK cells. To clarify the cytotoxic potential of ATLL cells, immunohistochemistry was performed in CD8+ and/or CD56+ ATLL cells, using anti-TIA-1, anti-granzyme B, anti-perforin and anti-FasL antibodies. We studied nine cases of CD8+ and/or CD56+ ATLL, all of which exhibited monoclonal integration of human T-cell leukaemia virus type 1 (HTLV-1) proviral DNA. Four cases exhibited a CD8+/CD56- phenotype, four others had a CD8-/CD56+ phenotype, and one was CD8+/CD56+. All but one case also expressed the surface antigens CD3, TCR alpha beta, and CD4. Expression of granzyme B and TIA-1 were demonstrated in three and two cases, respectively, but none expressed perforin or FasL. In the control study, 10 cases with typical CD3+/4+/8-/56- ATLL demonstrated no expression of those cytotoxic-associated proteins. Our findings suggest that CD8 and/or CD56 positivity probably confer(s) no cytotoxic function on ATLL cells, and it is possible that CD8 and CD56 may be simply aberrant surface markers in ATLL.

Adult↗
PubMed1999

Endothelium-dependent contraction induced by substance P in canine cerebral arteries: involvement of NK1 receptors and thromboxane A2.

We characterized the endothelial responses to substance P (SP) in the isolated canine cerebral artery. SP caused concentration-dependent contraction at 10(-10) - 10(-7) M and relaxation at 10(-10) and 10(-9) M, which were abolished by removal of the endothelium. The SP-induced endothelium-dependent relaxation (EDR) was suppressed, while the endothelium-dependent contraction (EDC) was increased by repeated application. The EDC induced by SP (10(-7) M) was attenuated by SR-140333 (10(-9) - 10(-7) M) and CP-99994 (10(-7) M), both NK1 antagonists, but not by SR-48968 (10(-7) M), an NK2 antagonist, or four antagonistic SP analogues (10(-6) M). The EDC induced by SP (10(-7) M) was attenuated by aspirin (10(-5) M), a cyclooxygenase inhibitor, OKY-046 (10(-5) M), a TXA2 synthetase inhibitor and ONO-3708 (10(-8) M), a TXA2 antagonist. Neurokinin A (10(-7) M) but not neurokinin B (10(-7) M) caused EDC similar to that induced by SP. In conclusion, SP induces EDC via endothelial NK1 receptors and TXA2 production in canine cerebral arteries.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1999

Basic fibroblast growth factor and fibrosis in Hodgkin's disease.

Hodgkin's disease (HD) is characterized by the presence of Hodgkin and Reed-Sternberg (H-RS) cells against a hyperplastic background of reactive cells such as lymphocytes, histiocytes, plasma cells, eosinophils, neutrophils and stromal cells. In addition, the HD nodular sclerosis (NS) subtype shows characteristic fibrous bundles, while the other subtypes do not. The fibrosis is considered to correlate with multiple cytokines and cytokine networks. Basic fibroblast growth factor (bFGF), one of the potent stimulators of fibroblasts, has also been linked to the fibroproliferative process. To investigate the relationship of fibrosis and bFGF, we thus performed both immunostaining, in situ hybridization (ISH) and reverse transcriptase-polymerase chain reaction (RT-PCR) on 25 cases of HD, which included 12 cases with NS subtype, 10 cases with mixed cellularity (MC), and 3 cases with lymphocyte predominance (LP). In NS, the expression of bFGF was stronger than that in LP and MC. In addition, the H-RS cells in NS frequently expressed bFGF. The stromal cells and histiocytes in the background expressed bFGF in NS. However, in MC and LP the number of bFGF-expressed H-RS cells was small, and the bFGF expression of background cells was rarely detected. However, the amount of bFGF varied in each case with HD NS. The above results support the possibilities that H-RS cells and background cells are a cellular source of bFGF and that the bFGF expression of those cells is also one of the influencing factors in the development of fibrosis in the HD NS subtype.

Adolescent↗