Biomedical subjects

M Abe

Publications and source records attributed to M Abe.

At least 667 records · Page 37Linked to original sources

PubMed1994

Diagnosis of t(2;5)(p23;q35)-associated Ki-1 lymphoma with immunohistochemistry.

Some Ki-1 lymphomas carry a specific chromosomal translocation, t(2;5)(p23;q35). We have recently found a novel hyperphosphorylated 80-kD protein tyrosine kinase, p80, in a human Ki-1 lymphoma with this translocation. Subsequent cDNA cloning showed that p80 is a fusion protein of two different genes on chromosome 2p23 and 5q35, the novel tyrosine kinase gene and nucleophosmin gene, respectively. In this study, we intended to detect p80 on lymphoma tissues with immunologic methods. Thus, we developed rabbit polyclonal antibody using a synthetic peptide corresponding to a part of its kinase domain. The antibody (anti-p80) immunoprecipitated and immunoblotted p80 specifically from AMS3. Then, to examine whether t(2;5)(p23;q35) was present on biopsied lymphomas, reverse transcriptase-polymerase chain reaction (RT-PCR) covering the fusion junction of p80 mRNA was performed. Among 10 Ki-1 lymphomas and 10 additional lymphomas other than the Ki-1 lymphomas, expression of p80 mRNA was detected in three cases exclusively. When these 20 cases and additional 30 lymphomas were immunostained with anti-p80, positive staining was noted exclusively in the three cases found by PCR to have harbored the p80 mRNA. Thus, the present immunostaining, as well as PCR, was shown to be efficient for detecting lymphomas producing this chimeric protein/mRNA.

Amino Acid Sequence↗

PubMed1994

Enhancer sequences of the DF3 gene regulate expression of the herpes simplex virus thymidine kinase gene and confer sensitivity of human breast cancer cells to ganciclovir.

A potentially novel therapeutic strategy for breast cancer treatment involves sensitization of tumor cells to chemotherapy through gene transfer. Clinical application of this approach, however, may be limited by the lack of target cell specificity of currently available gene delivery techniques. Development of vectors with tumor-selective gene expression could overcome this problem. The DF3/MUC1 gene encodes a high molecular weight mucin-like glycoprotein which is overexpressed at the transcriptional level in the majority of human breast cancers. To develop a breast tumor-selective enhancer, we cloned the upstream region of the DF3 gene and have identified a 114-base pair enhancer region that can modulate transcription from heterologous promoters. The present studies demonstrate that the DF3 enhancer sequences can direct selective gene expression in DF3-positive breast carcinoma cells. DF3-positive breast carcinoma cell lines transfected with herpes simplex virus thymidine kinase gene expression cassettes modified by the DF3 enhancer were markedly more sensitive to killing by ganciclovir than were the same cells transfected with the expression cassettes lacking the DF3 enhancer. DF3-negative cell lines transfected with the DF3 enhancer constructs, however, were no more sensitive to ganciclovir than were cells treated with the unmodified expression plasmids. Consistent with an innocent bystander effect, nontransfected human breast carcinoma cells were susceptible in a cell density-dependent manner to ganciclovir-induced cell killing when adjacent to transfected cells. The results also demonstrate that the DF3 enhancer sequences can be effectively incorporated into a retroviral vector to mediate selective gene expression following retroviral infection. These findings suggest that the DF3 promoter/enhancer may be useful for incorporation into vectors designed for gene therapy of breast cancer.

Base Sequence↗

PubMed1994

A novel membrane antigen selectively expressed on terminally differentiated human B cells.

A monoclonal antibody (MoAb) that defines a novel terminal B-cell-restricted antigen, termed HM1.24, was developed against a human plasma cell line. The MoAb, designated anti-HM1.24, reacted with five different human myeloma cell lines, as well as with monoclonal neoplastic plasma cells obtained from the bone marrow or peripheral blood of patients with multiple myeloma or Waldenström's macroglobulinemia. The HM1.24 antigen was also expressed by mature Ig-secreting B cells (plasma cells and lymphoplasmacytoid cells) but not by other cells contained in the peripheral blood, bone marrow, liver, spleen, kidney, or heart of normal individuals or patients with non-plasma-cell-related malignancies. The anti-HM1.24 MoAb bound to human myeloma RPMI 8226 cells with an affinity constant of 9.2 x 10(8) M-1, indicating approximately 84,000 sites/cell. By immunoprecipitation assay under reducing conditions, this MoAb identified a membrane glycoprotein that had a molecular weight of 29 to 33 kD. Our studies indicate that the HM1.24-related protein represents a specific marker of late-stage B-cell maturation and potentially serves as a target antigen for the immunotherapy of multiple myeloma and related plasma cell dyscrasias.

Animals↗

PubMed1994

The B7-2 (B70) costimulatory molecule expressed by monocytes and activated B lymphocytes is the CD86 differentiation antigen.

T-cell activation is initiated after T-cell receptor binding to antigen, but also requires interactions between costimulatory molecules expressed on antigen-presenting cells. An important costimulatory molecule expressed by monocytes and activated B lymphocytes has been recently identified and termed B7-2 or B70. Independently, a new Cluster of Differentiation was defined in the Fifth International Leukocyte Differentiation Antigen Workshop as CD86, a molecule predominantly expressed by monocytes and activated B lymphocytes. In this study, the two monoclonal antibodies that defined CD86, FUN-1 and BU-63, were shown to bind to cDNA transfected cells expressing B7-2/B70. The FUN-1 monoclonal antibody also completely blocked the costimulatory activity of B7-2/B70 in functional assays. Therefore, the serologically defined CD86 differentiation antigen is the B7-2/B70 molecule.

Animals↗

PubMed1994

The role of cerebrospinal fluid cytology in radiotherapy planning for intracranial germinoma.

PURPOSE: The association between the cerebrospinal fluid cytology findings and the clinical features of patients with intracranial germinoma was investigated to determine whether cerebrospinal fluid cytology could be helpful in determining the optimal radiation treatment volume. METHODS AND MATERIALS: Between 1976 and 1992, cerebrospinal fluid cytology was performed in 42 germinoma patients using a cytocentrifugation method. Forty patients received irradiation and 2 received chemotherapy with cisplatin and etoposide. RESULTS: Cerebrospinal fluid cytology was positive in 22 of the 42 patients (52%). Dissemination via cerebrospinal fluid (intraventricular or spinal) was present at the initial diagnosis in eight (36%) of the 22 cytology-positive patients and none of the 20 negative patients. After treatment, cerebrospinal fluid dissemination developed in four (18%) of the cytology-positive patients and one (5%) of the negative patients. Two of the former four patients had received chemotherapy alone as initial treatment. Five patients with positive cytology received irradiation to a smaller volume than the cerebrospinal axis (primary tumor site plus spinal axis in three and whole brain in two), but they have not developed recurrence in the 4 to 14 years since therapy. The 5-year survival rate was 93% for the cytology-positive patients and 94% for the negative patients. CONCLUSION: Cerebrospinal fluid cytology-positive patients have a higher risk of cerebrospinal fluid dissemination and it seems reasonable to give them low-dose (20-24 Gy) prophylactic craniospinal irradiation. When properly irradiated, the prognosis of cytology-positive patients is as good as that of negative patients.

Adolescent↗

PubMed1994

Fluorinated 2-nitroimidazole derivative hypoxic cell radiosensitizers: radiosensitizing activities and pharmacokinetics.

PURPOSE: To assess the effects of incorporation of a CF2 group into the side chain of a 2-nitroimidazole derivative, we evaluated the in vitro and in vivo radiosensitizing activities of KU-2285 (a 2-nitroimidazole derivative with an N1-substituent of -CH2CF2CONH(CH2)nOH, n = 2) and its related compounds in comparison with those of comparable nonfluorinated compounds. The pharmacokinetics of these compounds in murine tumors was also tested. METHODS AND MATERIALS: KU-2285, KU-3202 (n = 3) and KU-3207 (n = 4) are fluorinated 2-nitroimidazole derivative compounds with similar structures. Etanidazole (a 2-nitroimidazole derivative with an N1-substituent of -CH2CONH(CH2)nOH, n = 2) and its related compounds, KU-3205 (n = 3) and KU-3206 (n = 4) were also tested. The in vitro radiosensitizing activities of each compound for hypoxic cells was evaluated with a standard colony formation method. The in vivo radiosensitizing activities of these compounds were tested in female C3H/He mice bearing SCCVII tumors using an in vivo/in vitro clonogenic assay. The pharmacokinetic studies were performed in C3H/He mice bearing the SCCVII tumor. Samples were analyzed by reverse-phase high-performance liquid chromatography. RESULTS: The in vitro radiosensitizing activities of fluorinated 2-nitroimidazoles were higher than those of the nonfluorinated compounds. Although the in vivo radiosensitizing activity of KU-2285 was higher than that of etanidazole (p < 0.05), other fluorinated 2-nitroimidazoles showed less radiosensitizing activity than the comparable nonfluorinated compounds. The compound was eliminated from serum more rapidly with the increase in the number of CH2 group in the side chain of the compound in each series. CONCLUSION: Although the in vitro sensitizing activity of the fluorinated compounds was higher than that of the comparable nonfluorinated compounds, the in vivo radiosensitizing activity of all fluorinated compounds but KU-2285 was lower than that of comparable etanidazole group compounds, probably due to their lower molecular concentrations in tumor and rapid elimination.

Animals↗

PubMed1994

Reoxygenation in the SCCVII tumor after KU-2285 sensitization plus single or fractionated irradiation.

PURPOSE: Because reoxygenation of solid tumors after irradiation with a hypoxic cell sensitizer has never previously been investigated, we assessed the reoxygenation in SCCVII tumors after treatment with KU-2285 plus single or fractionated irradiation. METHODS AND MATERIALS: KU-2285 (100 mg/kg) was injected intraperitoneally into C3H mice bearing 1-cm SCCVII tumors at 30 min before a single dose of 12 Gy or three fractions of 5 Gy at 12 h intervals. Changes of the hypoxic fraction (HF) were then evaluated by the paired survival curve method. RESULTS: Since the radiosensitizing effect of KU-2285 was relatively persistent, the HF was only evaluable after 6 h of irradiation. The HF of untreated SCCVII tumors was 9.1%. After treatment with KU-2285 and 12 Gy, the HF was 25% at 6 h, 32% at 12 h, 24% at 24 h, and 7.6% at 72 h. The HF was lower at 6 h than that after radiation alone, but was similar at later periods. After three fractions of 5 Gy with or without KU-2285, the HF was 33% at 6 h in both groups, while it was 12% and 13% at 24 h for tumors pretreated with KU-2285 and those receiving radiation alone, respectively. However, a sensitizing effect of KU-2285 was indicated by the downward shift of the survival curves for tumors irradiated after exposure to this agent. CONCLUSION: Reoxygenation occurred quite efficiently in tumors receiving KU-2285 and 12 Gy. After fractionated irradiation, however, reoxygenation was similar in the KU-2285-pretreatment and irradiation alone groups.

Animals↗

PubMed1994

Comparison of radiosensitizing effect of KU-2285 and SR-2508 at low drug concentrations and doses.

PURPOSE: Since the radiosensitizing effect of KU-2285 at relatively low dose levels is not known, we investigated its efficacy at such low concentrations or doses achievable in humans with oral administration of 0.3-1.0 g/m2. METHODS AND MATERIALS: KU-2285 was tested in comparison with SR-2508 at low concentrations (0.05-0.25 mM) in vitro by the cytokinesis-block micronucleus assay and by the colony formation assay, and at low drug doses (12.5-50 mg/kg) in vivo by the in vivo-in vitro assay and by the growth delay assay using SCC VII tumors in C3H/He mice. RESULTS: In the cytokinesis-block micronucleus assay, the sensitizer enhancement ratio (SER) for KU-2285 and SR-2508 was 1.43 and 1.17 at 0.05 mM, 1.75 and 1.27 at 0.10 mM, and 2.14 and 1.69 at 0.25 mM, respectively. In the colony formation assay, the SER for KU-2285 was also greater than that for SR-2508. In the in vivo-in vitro assay, the SER for KU-2285 and SR-2508 was 1.11 and 1.04 at 12.5 mg/kg, 1.21 and 1.04 at 25 mg/kg, and 1.26 and 1.18 at 50 mg/kg, respectively. In the growth delay assay at 50 mg/kg, no tumor regrowth was observed in four of the 18 mice treated with KU-2285 + 25 Gy, although the growth delay time for the remaining mice was similar to that for SR-2508 + 25 Gy. CONCLUSION: KU-2285 was more effective than SR-2508 both at low drug concentrations in vitro and at low drug doses in vivo. These promising findings suggest the potential superiority of KU-2285 over SR-2508 as a radiosensitizer for clinical use.

Animals↗

PubMed1994

Radiosensitizing activity and pharmacokinetics of multiple dose administered KU-2285 in peripheral nerve tissue in mice.

PURPOSE: In a clinical trial in which a 2-nitroimidazole radiosensitizer was administered repeatedly, the dose-limiting toxicity was found to be peripheral neuropathy. In the present study, the in vivo radiosensitizing activity of KU-2285 in combination with radiation dose fractionation, and the pharmacokinetics of cumulative dosing of KU-2285 in the peripheral nerves were examined. METHODS AND MATERIALS: The ability of three nitroimidazoles, misonidazole (MISO), etanidazole (SR-2508) and KU-2285, to sensitize SCCVII tumors to radiation treatment has been compared for drug doses in the range 0-200 mg/kg. Single radiation doses or two different fractionation schedules (6 Gy/fractions x three fractions/48 h or 5 Gy/fractions x five fractions/48 h) were used; the tumor cell survival was determined using an in vivo/in vitro colony assay. The pharmacokinetics in the sciatic nerves were undertaken, when KU-2285 or etanidazole were injected at a dose of 200 mg/kg intravenously one, two, three or four times at 2-h intervals. RESULTS: At less than 100 mg/kg, KU-2285 sensitized SCCVII tumors more than MISO and SR-2508 by fractionated irradiation. Evaluation of pharmacokinetics in the peripheral nerves showed that the apparent biological half-life of SR-2508 increased with the increases in the number of administrations, whereas that of KU-2285 became shorter. CONCLUSION: Since most clinical radiotherapy is given in small multiple fractions, KU-2285 appears to be a hypoxic cell radiosensitizer that could be useful in such regimens, and that poses no risk of chronic peripheral neurotoxicity.

Animals↗

PubMed1994

KIN-804 vs. KU-2285 as a radiosensitizer for clinical use.

PURPOSE: The in vitro and in vivo effects of two promising hypoxic cell radiosensitizers, KIN-804 (KIN) and KU-2285 (KU), were compared using four types of assays, and the acute toxicity and pharmacokinetics of KIN were investigated to evaluate the clinical applicability of the compounds. METHODS AND MATERIALS: To evaluate the in vitro effect at low radiation doses (1-4.5 Gy), the cytokinesis-block micronucleus (MN) assay using SCCVII or EMT-6 cells and the chromosomal aberration (CA) assay using EMT-6 cells were performed. In addition, an in vivo-in vitro colony assay, a growth delay assay, and a pharmacokinetic study were performed using C3H mice bearing SCCVII tumors, and the LD50/7 was determined in ICR mice. RESULTS: In the in vitro MN assay, the sensitizer enhancement ratio (SER) at 0.1, 0.25, 1, and 5 mM with SCCVII cells, and at 1 mM with EMT-6 cells was respectively, 1.45, 1.61, 2.57, 4.22, and 1.96 for KIN, and 1.57, 1.62, 2.59, 5.66, and 2.21 for KU. In the in vitro CA assay, the SER at 1 mM was 1.78 for KIN and 1.79 for KU. In the in vivo-in vitro colony assay, the SER of KIN at 50, 100, and 200 mg/kg was 1.24, 1.30, and 1.45, respectively, while the SER of KU at 100 mg/kg was 1.41. In the growth delay assay, the growth delay time for 100 and 200 mg/kg of the drug plus 20 Gy of radiation was respectively, 16.5 and 19.1 days for KIN, and 18.9 and 24.0 days for KU. In all experiments, the sensitizing effect of KIN was almost equal to that of KU. The LD50/7 of KIN was 3.6 g/kg by intraperitoneal injection, while that of KU was 3.6 g/kg by intraperitoneal injection, and the pharmacokinetic study of KIN revealed a low uptake of the drug by the brain. CONCLUSION: Both KIN and KU had a definite sensitizing effect even at lower drug concentrations or doses, suggesting their potential usefulness in clinical radiotherapy.

Animals↗

PubMed1994

The radiosensitivity of quiescent cell populations in murine solid tumors in irradiation with fast neutrons.

PURPOSE: We analyzed the characteristics of radiosensitivity and potentially lethal damage repair in the quiescent cell populations of murine SCC VII solid tumors irradiated with fast neutrons, in comparison with those irradiated with 10 MV X rays. METHODS AND MATERIALS: SCC VII tumor-bearing C3H/He mice were irradiated with 30 MeV fast neutrons or 10 MV X rays after receiving 10 injections of 5-bromo-2'-deoxyuridine (BUdR) to label all proliferating tumor cells. Immediately or 24 h after irradiation, the tumors were excised and trypsinized. The tumor cell suspensions thus obtained were incubated with cytochalasin-B (a cytokinesis blocker), and the micronucleus frequency in cells without BUdR labeling was determined using immunofluorescence staining to BUdR. This micronucleus frequency was then used to calculate the surviving fraction of unlabeled cells from the regression line for the relation between micronucleus frequency and the surviving fraction of all tumor cells. Thus, a cell survival curve could be determined for the cells not labeled by BUdR, which can be regarded as the quiescent cells for all practical purposes. RESULTS: The difference in intrinsic radiosensitivity between all tumor and quiescent cells became smaller by using fast neutrons, compared with X rays, especially when large radiation doses were given. Potentially lethal damage repair by quiescent cells was less evident following irradiation with fast neutrons than with X rays, especially when large doses were delivered. CONCLUSION: By using fast neutrons in clinical radiotherapy, the radiosensitivity of solid tumors is thought to depend on their heterogeneity less critically than for X rays.

Animals↗

PubMed1994

An assay for transforming growth factor-beta using cells transfected with a plasminogen activator inhibitor-1 promoter-luciferase construct.

Transforming growth factor-beta (TGF-beta) is a potent regulator of cellular differentiation, proliferation, migration, and protein expression. These properties have been exploited to create a variety of bioassays for detecting the mature growth factor. In this paper, we describe a highly sensitive and specific, nonradioactive quantitative bioassay for TGF-beta based on its ability to induce plasminogen activator inhibitor-1 (PAI-1) expression. Mink lung epithelial cells (MLEC) were stably transfected with an expression construct containing a truncated PAI-1 promoter fused to the firefly luciferase reporter gene. Addition of TGF-beta (0.2 to > 30 pM) to the transfectants resulted in a dose-dependent increase in luciferase activity in the cell lysates. Although responsive to TGF-beta, this promoter fragment was only minimally influenced by other known inducers of PAI-1 expression. When compared to the widely used MLEC assay, this assay demonstrated greater sensitivity and specificity, allowing quantification of TGF-beta in complex biological solutions.

Animals↗

PubMed1994

Effects of tiludronate on bone mass, structure, and turnover at the epiphyseal, primary, and secondary spongiosa in the proximal tibia of growing rats after sciatic neurectomy.

To evaluate the effects of tiludronate on the mass, structure, and turnover of cancellous bone regions in immobilized rat tibiae, we performed a 4 week dosing experiment. The right hindlimbs of 84 Sprague-Dawley rats (5 weeks old) wee neurectomized or sham operated. Animals were assigned to seven groups (n = 12 each); group 1 was sham operated, and groups 2-7 were neurectomized. Groups 1 and 2 were given vehicle only (distilled water), and groups 3, 4, and 5 were given tiludronate orally at doses of 25, 50, and 100 mg/kg body weight (BW)/day, respectively, throughout the experimental period. Group 6 was given 100 mg/kg BW/day of the agent for the first 2 weeks only, and group 7 received vehicle only for the first 2 weeks and then 100 mg/kg BW/day of the agent for the last 2 weeks. After tetracycline labeling was performed, the right tibiae were removed from the animals and processed to yield undecalcified sections. Histomorphometry was performed in the epiphyseal, primary, and secondary spongiosa of the proximal tibia. In group 2, trabecular bone volume (BV/TV) and trabecular number (Tb.N) were significantly decreased in the primary and secondary spongiosae, but this did not occur in the epiphyseal spongiosa. Osteoid surface (OS/BS) was decreased and osteoclast surface (Oc.S/BS) was increased in the secondary spongiosa. Tiludronate increased BV/TV and Tb.N in the primary spongiosa by reducing the values for the parameters of osteoclast surface (Oc.S/BS) and osteoclast number (Oc.N/BS). Osteoid surface in this region was not decreased by the agent. In groups 4 and 5, tiludronate prevented bone loss in the secondary spongiosa by reducing both OS/BS and Oc.S/BS. In group 6, BV/TV in the primary spongiosa was maintained at the level of group 1, but Oc.S/BS and Oc.N/BS were elevated. In the secondary spongiosa, bone mass was preserved and the reduction in these parameters was maintained. In group 7, however, BV/TV was increased in the primary spongiosa as a result of a reduction in osteoclastic resorption; in the secondary spongiosa, however, BV/TV was decreased and trabecular turnover was not reduced at the end of the experiment in these growing animals. Mineral apposition rates were not reduced by tiludronate. This study clearly demonstrated that this agent prevented immobilization bone loss by inhibiting resorption.(ABSTRACT TRUNCATED AT 400 WORDS)

Administration, Oral↗

PubMed1994

Variable-region subgroup distribution among lambda-type immunoglobulins in normal human serum.

The distribution of the major VL subgroups (V lambda I, V lambda II, V lambda III, V lambda IV, V lambda VI, and V lambda VIII) among lambda-type immunoglobulins (Igs) in normal serum was determined by a sandwich enzyme-linked immunosorbent assay (ELISA) using a panel of murine anti-human V lambda-subgroup-specific monoclonal antibodies (MoAbs) and appropriate reference standard proteins. The mean concentration of lambda I, lambda II, lambda III, lambda IV, lambda VI, and lambda VIII Igs in serum specimens obtained from 23 adults was 2158, 162, 1958, 264, 225, and 169 micrograms/mL and represented 44, 3, 40, 5, 5, and 3% of the total Ig lambda population, respectively. The low percentage of lambda II Igs in normal serum was in marked contrast to the approximately 40% incidence of this V lambda subgroup found among lambda-type Bence Jones proteins and monoclonal serum Igs obtained from patients with multiple myeloma and AL amyloidosis, or approximately 60% in Waldenström's macroglobulinemia. The non-random expression of the V lambda II subgroup in these diseases implies a relationship between V lambda-gene usage and plasma cell, as well as certain types of lymphocytic dyscrasias.

Adult↗

PubMed1994

Production of two monoclonal antibodies (FB1 and FB21) useful for the identification of human B lymphocytes in formalin-fixed, paraffin-embedded tissues.

Two monoclonal antibodies (FB1 and FB21) reactive in formalin-fixed, paraffin-embedded tissue sections are reported in this paper. FB1 and FB21 recognize a cytoplasmic antigen and a surface antigen of B cells, respectively. FB1 reacts with mantle zone (MZ) B cells, germinal centre (GC) cells, and marginal zone (MrZ) B cells, but not with T cells in lymphoid tissues. FB21 reacts with MZ B cells, GC cells in lymphoid tissues, and T cells of peripheral blood, but not with MrZ B cells in the spleen. Neither monoclonal antibody (MoAb) reacts with monocytes, granulocytes, or plasma cells. FB1 reacted with all the B-cell lymphomas tested and with CD20-positive Reed-Sternberg cells in two of five cases of Hodgkin's disease, but not with multiple myelomas or T-cell lymphomas. FB21 reacted with B-cell lymphoma in 20 of 22 cases, but not with multiple myelomas, T-cell lymphomas, or Reed-Sternberg cells of Hodgkin's disease. Immunoprecipitation studies revealed that FB1 recognizes the same two polypeptide chains that are recognized by L26 and is a member of the CD20 antibody cluster. FB21 was thought to recognize a sialic acid-dependent carbohydrate epitope and this was confirmed at the Fifth International Conference on Human Leukocyte Differentiation Antigens (Boston, 1993). FB21 did not react with splenic MrZ B cells and was different from the pan B markers reported previously [CD20 (L26), CD45RA (MB1), and CD74 (LN-2)]. FB21 recognizes a subset of B cells and appears to be closely related to CD75/76 antibodies. FB1 and FB21 are useful MoAbs for the diagnosis and analysis of B-cell lymphomas.

Animals↗

PubMed1994

A unique murine CD43 epitope Lp-3: distinct distribution from another CD43 epitope S7.

In foregoing studies, we found a unique B cell differentiation antigen Lp-3 which is expressed on pre-B and premature B cells in the bone marrow, but is negative on bone marrow mature B cells and peripheral resting B cells. Nonetheless, Lp-3 was clearly positive on the majority of CD5 B(B1) cells. When we examined the biochemical nature and partial amino acid sequences of purified 132-kDa Lp-3 molecules and the nucleotide sequence of the cDNA clones, we found that Lp-3 is an epitope of CD43. Thus, the monoclonal antibody (mAb) Lp-3 may be the first mAb to murine CD43 defined by primary target structure analysis. Comparison of tissue distribution of Lp-3 and S7, an epitope previously suggested to associate with murine CD43, showed that they were similarly distributed on thymocytes, peripheral B and T cells, granulocytes, and platelets. In the bone marrow, while both Lp-3 and S7 were negative on mature B cells, the former was positive on all B lineage cells at an early ontogeny and the latter was positive only on the minor population of pre-B cells and pro-B cells. Lp-3 and S7 epitopes also showed different distributions on basement membranes of renal glomerulus, bronchus, and endometrium, lining cells of choroid plexus and muscular cells of arterioles in a variety of tissues. As CD43 has various isoforms generated by different degrees of glycosylation of the common core peptide, it is likely that Lp-3 and S7 are associated with different CD43 isoforms.

Amino Acid Sequence↗

PubMed1994

Preferential expression of human lambda-light-chain variable-region subgroups in multiple myeloma, AL amyloidosis, and Waldenström's macroglobulinemia.

We have compared the distribution of lambda-light-chain variable-region (V lambda) subgroups among Ig lambda molecules found in the serum of normal individuals with that of monoclonal Ig lambda components obtained from patients with plasma cell and related immunoproliferative disorders. A panel of monoclonal antibodies specific for each of the major human V lambda subgroups--V lambda I, V lambda II, V lambda III, V lambda IV, V lambda VI, and V lambda VIII--was used in a highly sensitive enzyme-linked immunosorbent assay (ELISA) to quantitate each of these populations. The mean distribution of Ig lambda I, Ig lambda II, Ig lambda III, Ig lambda IV, Ig lambda VI, and Ig lambda VIII molecules in serum specimens collected from 20 normal adults was approximately 40, 3, 43, 5, 5, and 3% of the total Ig lambda population, respectively. In contrast, that of monoclonal IgG, IgA, and IgD proteins and Bence Jones proteins obtained from patients with multiple myeloma and related gammopathies (n = 196) was approximately 27, 28, 39, 5, 0, and 1%, respectively. The percentage of monoclonal Ig lambda II components found in individuals with AL lambda amyloidosis (n = 41) was comparably increased to that seen in multiple myeloma and was even higher in patients with Waldenström's macroglobulinemia (n = 16), in whom 63% of the IgM lambda proteins were of the V lambda II subgroup. Also evidenced were differences in the distribution of other V lambda subgroups in the disease states: Most striking was the predominance (41%) of the V lambda VI subgroup among monoclonal lambda chains obtained from patients with AL amyloidosis and that this subgroup was found exclusively on amyloidosis-associated proteins. No Ig lambda VI-type myeloma- or macroglobulinemia-related proteins were identified. The observed alterations in V lambda subgroup distribution among "pathologic" monoclonal Igs were attributed to the particular disease and not related to the heavy-chain class. Our finding that certain V lambda subgroups are nonstochastically expressed in lambda-type multiple myeloma, AL amyloidosis, and Waldenström's macroglobulinemia provides evidence for abnormal VL gene usage in these disorders and, thus, furnishes new insight into their pathogenesis.

Amyloid↗

PubMed1994

Gaucher's disease, type I (adult type), with massive involvement of the kidneys and lungs.

A 33-year-old Japanese male, first diagnosed as having Gaucher's disease at the age of 3 years, died of renal and pulmonary failure. Autopsy findings disclosed the proliferation of Gaucher's cells in the liver, bone marrow, lymph nodes, kidneys and lungs. Electron-microscopical findings suggested that the Gaucher's cells observed in the renal glomeruli might be derived from circulating macrophages.

Adult↗