Biomedical subjects

M Abe

Publications and source records attributed to M Abe.

At least 577 records · Page 32Linked to original sources

PubMed1996

[Lipoid pneumonia combined with pulmonary nocardiosis caused by inhalation of amphotericin-B after renal transplantation].

A 35-year-old woman was admitted to our hospital because of a fever and a productive cough. She had undergone renal transplantation and had taken immunosuppressive drugs, a steroid, inhaled amphotericin-B, and pentamidine. She was treated with ganciclovir, because infection with cytomegalovirus was suspected but her symptoms did not resolve. A chest X-ray film and a computed tomogram showed an infiltrative shadow in the right lower lung field. Specimens obtained by transbronchial lung biopsy showed lipid-laden macrophages and oil droplets in alveolar spaces. Organisms of the genus nocardia were isolated from bronchial lavage fluid. The final diagnosis was lipoid pneumonia combined with pulmonary nocardiosis. After treatment with Imipenem.cilastatin sodiom, Exacin and Sulfamethoxazole.trimethoprim, her symptoms and the infiltrative shadows on the chest X-ray film resolved. We believe that this patient had an exogenous lipoid pneumonia caused by inhalation of deoxycholic acid in amphotericin-B solubilized liquid, in addition to pulmonary nocardiosis.

Administration, Inhalation↗

PubMed1996

Tirapazamine: hypoxic cytotoxicity and interaction with radiation as assessed by the micronucleus assay.

We investigated the cytotoxicity and the interaction with low-dose radiation (1-4Gy) of tirapazamine by the in vitro cytokinesis-block micronucleus (MN) assay. Murine SCCVII and human melanoma (G-361) cells were treated with tirapazamine under aerobic or hypoxic conditions for 1 h and the MN frequency was determined using cytochalasin-B. The cells were also treated with or without tirapazamine or KU-2285 (hypoxic cell sensitiser) under hypoxic conditions and irradiated with or without reaeration of the cell suspensions. A dose-dependent increase of MN frequency was observed by tirapazamine treatment and the hypoxic toxicity ratio was about 130 for SCCVII and 37 for G-361. The radiation dose-response curves of MN frequency suggested that the interaction of tirapazamine with irradiation appeared to be essentially additive in both cell lines. In contrast, the dose-response curve became steeper by KU-2285 treatment. Combined effects of tirapazamine and irradiation on the hypoxic cells were much higher than the radiation effect on aerobic cells at low doses, while the effects of KU-2285 did not exceed that of aerobic irradiation. In conclusion, tirapazamine appeared to be superior to hypoxic radiosensitisers at clinically relevant doses, not because of aerobic radiosensitisation but because of its potent hypoxic cytotoxicity additive to radiation effect.

Animals↗

PubMed1996

Novel benzodioxan derivative, 5-[3-[((2S)-1,4-benzodioxan-2-ylmethyl) amino]propoxy]-1,3-benzodioxole HCl (MKC-242), with anxiolytic-like and antidepressant-like effects in animal models.

Behavioral effects of MKC-242 (5-{3-[((2>)-1,4-benzodioxan-2-ylmethyl)amino] propoxy}-1,3-benzodioxole CHl), a novel and selective serotonin 1A receptor agonist, were investigated in rats and mice and compared against those of diazepam, buspirone and tandospirone. MKC-242 (0.0625-0.25 mg/kg, p.o.) significantly increased punished drinking in water-deprived rats. The reference compounds also increased punished drinking at doses of 10 to 40 mg/kg, p.o. The increase by MKC-242 was blocked by N-tert-butyl-3-(4-(2-methoxypenyl)piperazin-1-yl) -2-phenylpropanamide, a serotonin 1A receptor antagonist. MKC-242 (0.1-0.5 mg/kg, p.o.) also increased social interaction under high light and unfamiliar conditions in rats. It had weak benzodiazepine-like side effects in mice. MKC-242 (1, 3 mg/kg, p.o.) attenuated the reduction of locomotion caused by restraint stress in rats, the same effects were observed on both buspirone (100 mg/kg, p.o.) and tandospirone (100 mg/kg, p.o.). In the forced swimming test in rats, MKC-242 (0.3-3 mg/kg, i.p.), 8-hydroxy-2-(di-n-propylamino) tetralin (1, 3 mg/kg, i.p.) and amitriptyline (30 mg/kg, i.p.) reduced immobility, although diazepam, buspirone and tandospirone did not. The reduction by MKC-242 and 8-OH-DPAT was antagonized by N-tert-butyl-3-(4-(2-methoxyphenyl)piperazin-1-yl) -2-phenylpropanamide. Moreover, the reduction was also blocked by 1-(2--pyrimidinyl)piperazine (1-PP), a common metabolite of buspirone and tandospirone. These findings suggest that MKC-242 possesses potent anxiolytic and antidepressant properties that are mediated via an activation of serotonin 1A receptors.

Animals↗

PubMed1996

[Sinus venosus atrial septal defect: report of two cases with successful repair by the Vargas' procedure].

Two cases of sinus venosus atrial septal defect with partial anomalous of right upper pulmonary venous drainage into superior vena cava treated by the Vargas' procedure were reported. These patients were 5 and 6 years old. Post operative courses were uneventful, and results of postoperative hemodynamic and clinical evaluation were encouraging. The Vargas' procedure is useful method for a reconstraction of the anomaly in childhood because of use of the autologus tissues. Though long-term fate of this procedure is still uncertain. Then, we consider that a long-term follow up is necessary.

Cardiac Surgical Procedures↗

PubMed1996

Kyoto University experience with intraoperative radiation therapy.

To date, intraoperative radiotherapy has been performed at Kyoto University Hospital in a total of 480 patients with malignancies various sites. Among these, patients with disease of 4 major sites were selected for prognostic analysis. For gastric cancer patients survival was improved by the adjuvant intraoperative radiotherapy compared with gastrectomy alone in those with advanced nodal or serosal involvement [P < 0.05 for n2 + n3' 0.1 > P > 0.05 for s(+)]. Also, the survival for the adjuvant radiotherapy group was significantly improved in patients with stage II-III pancreatic cancer who underwent non-curative resection (P < 0.001). For patients with soft tissue sarcomas of the extremities, intraoperative radiotherapy was performed after the tumours were surgically removed to the greatest e* possible. Operation curability had a great impact on the local tumour control rate (82% for curative resection versus 18% for non-curati resection) and on the long-term survival rates (65% versus 8%, respectively). In patients with osteosarcoma, a large single do* 50-55 Gy was applied to the affected limb in an attempt to achieve local control and limb salvage. By this method, good local control attained, and a 10-year survival rate showed improvement following the introduction of cisplatinum into intensive chemotherapy.

Bone Neoplasms↗

PubMed1996

[A case report of a successful surgery for thoracoabdominal aortic aneurysm under partial cardiopulmonary bypass with selective perfusion of major abdominal branches].

A 69-year-old man showed gradually developing thoracoabdominal aortic aneurysm (TAAA) after coronary artery bypass grafting. The patient underwent graft replacement of TAAA uneventfully under partial cardiopulmonary bypass with selective perfusion of major abdominal branches. The major abdominal branches and two pairs of intercostal arteries were reconstructed. The patient showed no organ failure or spinal damage postoperatively. Partial cardiopulmonary bypass with selective perfusion of abdominal branches successfully protected both the visceral organs and the spinal cord from ischemia in a TAAA surgery.

Aged↗

PubMed1996

Effects of a high-protein diet on mineral metabolism and struvite activity product in clinically normal cats.

OBJECTIVE: To examine effects of high-protein diets (> 50% crude protein of dry matter) on urinary mineral excretion and struvite activity product ([Mg2+] x [NH4+] x [PO(4)3-]). ANIMALS: 14 clinically normal cats, 4 adult female and male cats for experiments 1 and 2, respectively, and 6 female kittens aged 4 months for experiment 3. PROCEDURE: Relations between dietary protein amount (25.9, 38.3, 51.4, and 65.4% crude protein [dry matter]) and urinary excretion of Mg, P, and Ca were examined in a 4 x 4-Latin square design (experiment 1). Struvite activity product, the index of solubility of struvite crystals, was determined when a high-protein diet (54.9%) was fed (experiment 2). Utilization of minerals in cats fed a high-protein diet long term was examined (experiment 3). RESULTS: Water intake and urine volume increased with increasing dietary protein concentration. Urinary Mg2+ excretion was not affected (experiment 1) or was decreased (experiment 3) by higher protein intake, leading to lower urine Mg2+ concentration in groups fed higher protein amounts. Urine pH was decreased by high-protein intake. As a result, PO(4)3- concentration was decreased by high-protein intake (experiment 2), although total daily urinary excretion of P was increased. Consequently, struvite activity product tended to decrease in cats fed high-protein diets, indicating increase in struvite solubility. High-protein intake decreased Ca and P retention by increasing their fecal and urinary excretions, respectively. CONCLUSION: As a consequence of the increase in urine volume and urine acidification, high-protein diets have potential ability to increase solubility of struvite crystals.

Animals↗

PubMed1996

[Home terminal care for lung cancer--subcutaneous injection with morphine hydrochloride for cancer related pain from metastatic bone cancer in a terminal lung cancer patient].

Home management for cancer-related pain in a terminal cancer patient is usually performed by oral or intrarectal administration with analgesics. If such treatment fails to reduce cancer-related pain, we have to treat them with epidural, intravenous or subcutaneous injection of these agents in some cases. We encountered a terminal lung cancer patient with metastatic bone cancer who was treated with continuous subcutaneous injection of morphine hydrochloride at home. As a result, the patient's quality of life has been remarkably improved. The management of cancer-related pain with analgesics and terminal care at home are discussed.

Aged↗

PubMed1996

[Awareness of health and welfare planning for elderly and methods to increase awareness: based on social marketing].

To clarify the socio-psychological factors affecting awareness of health and welfare planning for the elderly, a survey of community residents was performed in the Tokyo metropolitan area. The results obtained were as follows: 1. There were three factors which affected awareness concern about health and welfare services for the elderly as a social issue: concern about the local community; and concern about the local government. 2. Two other factors which did not affect the level of awareness were: anxiety about the health and welfare services for the elderly as a personal issue; and having personal experience of nursing care. From these results, a method to increase awareness was studied based on social marketing methods. Two primary target groups for increasing awareness were identified. One target was people who have the socio-psychological factors described above. Another target was people who have the potential need for health and welfare services but who were not aware of it. That is, they have relatively high anxiety about health and welfare services for the elderly as a personal issue and have personally experienced nursing care. The method of approach for these targets were studied. For the first group, the amount of the information available seemed to be important because these persons are ready to recognize the need for planning. Therefore, efficient information channels should be selected. For the second group, approaches that generate greater consumer participation by presenting this as an efficient method for solution of the problem should be adopted.

Adult↗

PubMed1995

Reconstitution ratio is critical for alloreactive T cell deletion and skin graft survival in mixed bone marrow chimeras.

Although allogeneic bone marrow (BM) transplantation is an effective way to induce donor-specific tolerance, its clinical application is hampered because of the risk associated with vigorous myeloablative pretransplant conditioning. One approach to overcome this problem is to establish a lower chimeric state by mild myeloablation. It is not clear, however, whether there is a threshold in the extent of chimerism that is required for tolerance induction. In this study, we establish a mixed BM chimera system to examine the correlation between the reconstitution ratio of BM chimerism, donor-reactive T cell deletion, and skin graft acceptance using I-E alpha transgenic C57BL/6 mice as the BM and skin graft donors and Ly5 congenic C57BL/6 mice as the recipients. In this system, the class II MHC molecule I-E was the transplantation Ag, and the extent of I-E-reactive T cell deletion was determined by flow cytometry using a mAb specific for the V beta 11 TCR. The degree of BM chimerism was measured by examining the expression of donor-derived Ly5.2 and host-derived Ly5.1 on peripheral blood cells. Transplantation of I-E+ transgenic donor BM cells resulted in deletion of V beta 11+CD4+ T cells in recipient's PBL, and the extent of deletion was proportional to the degree of chimerism. When mice of different degrees of chimerism were tested for skin graft survival, we found that recipient mice with > 30% chimerism could accept skin grafts from I-E+ donor mice, whereas those with < 10% chimerism showed prolonged but not permanent graft survival. These findings revealed the sequence of events for induction of tolerance. First, the degree of BM chimerism determines the number of I-E+ cells in the thymus, which then elicits negative selection of I-E-reactive T cells in a form of clonal deletion. The extent of T cell deletion ultimately determines the mode of tolerance. These data provide experimental evidence for the potential use of partial chimerism by bone marrow transplantation for the induction of donor-specific tolerance in clinical settings.

Animals↗

PubMed1995

Isolation and characterization of two distinct cDNA clones encoding corn seed cysteine proteinases.

We obtained two cDNA clones encoding corn seed cysteine proteinases (CCP1 and CCP2). Sequence analysis showed that CCP1 consists of 371 amino acid residues, in a prepro-protein form, with two unique short insertions in the mature protein region that are not found in papain or other common CPs. CCP2 consists of 360 amino acid residues with a vacuole sorting signal in the pro-sequence region. An amino acid sequence similarity of 42% was found between the mature protein region of CCP1 and that of CCP2. Although CCP1 is highly homologous to pea 15a CP (72%) and Arabidopsis thaliana RD 19 CP (79%), both of which are known to be induced only when the plant is exposed to a dehydrated environment, it showed very low homologies to other known cysteine proteinases (38-43%). CCP2 showed as much as 87% and 89% identity to rice oryzain gamma and barley aleurain, respectively. We also observed that the CCP1 mRNA is expressed in ripened corn seeds, although its expression reaches a maximum 5 days after the onset of germination. On the other hand, the CCP2 mRNA is expressed only during germination, with maximum expression at the 3-day stage. These results suggest the presence of at least two cysteine proteinases playing differential roles in the corn seeds.

Amino Acid Sequence↗

PubMed1995

Anaplastic large cell lymphomas expressing the novel chimeric protein p80NPM/ALK: a distinct clinicopathologic entity.

Anaplastic large cell lymphoma (ALCL) is a subtype of non-Hodgkin's lymphoma characterized by the CD30+ large neoplastic cells and sometimes carries a t(2;5)(p23;q35). Recently, we found a novel hyperphosphorylated 80-kD protein tyrosine kinase, p80, in ALCLs with t(2;5). Subsequent cDNA cloning showed p80 to be a fusion protein of two genes, the novel tyrosine kinase gene and the nucleophosmin gene, in accordance with the sequence of the NPM/ALK gene (Morris et al, Science 263:1281, 1994). Meanwhile, the clinicopathologic features of p80-carrying ALCLs have remained unclear. Paraffin sections of 105 cases of ALCL were immunostained using anti-p80 antibody, and 30 of them were shown to express p80. Clinicopathologic comparison between p80-positive and -negative ALCLs showed that p80-positive cases occurred in a far younger patient age group (16.2 +/- 12.9 years; p80-negative cases, 51.0 +/- 22.3 years; P < .0001) and the patients showed a far better 5-year survival rate (79.8%; p80-negative group, 32.9%; P < .01). These data showed that p80-positive ALCL is a distinct entity both clinically and pathogenetically and should be differentiated from p80-negative ALCL.

Adolescent↗

PubMed1995

Optical isomers of a new 2-nitroimidazole nucleoside analog (PR-350 series): radiosensitization efficiency and toxicity.

PURPOSE: A new 2-nitroimidazole nucleoside radiosensitizer, PR-350 (1-[1',3',4'-trihydroxy-2'-butoxy]-methyl-2-nitroimidazole), has been reported to be as efficient as and less toxic than etanidazole. This compound is racemic, and it was recently optically resolved into two isomers, PR-68 (2'R,3'S type) and PR-69 (2'S,3'R type). The other two isomers, PR-28 (2'S,3'S type) and PR-44 (2'R,3'R type), were asymmetrically synthesized. In the present study, we investigated the properties, sensitizing activity, and toxicity of PR-350 and the four optical isomers in comparison with those of other 2-nitroimidazole hypoxic cell radiosensitizers, etanidazole, KU-2285, KIN-804, and RP-170. Because PR-350 and PR-28 can be industrially synthesized, we evaluated whether either of these two drugs are suitable for further investigation. METHODS AND MATERIALS: In an in vitro study, EMT-6 cells were irradiated at a dose of 1-3 Gy under hypoxic conditions in the presence of the drugs at a concentration of 1 mM. A combined cytokinesis-block micronucleus and chromosomal aberration assay was performed. To assess the in vivo effects, colony assay and growth delay assay were performing using SCCVII tumor-bearing C3H mice. The mice received 16-24 GY 10-40 min after administration of 50-200 mg/kg of the drugs. Toxicity and pharmacokinetics in mice were also investigated. RESULTS: The sensitizer enhancement ratio (SER) in the in vitro cytokinesis-block micronucleus assay increased in the following order: PR-69 (1.27) approximately equal to PR-28 (1.31) approximately equal to PR-44 (1.38) approximately equal to PR-350 (1.41) approximately equal to PR-68 (1.47) < etanidazole (1.79) < KIN-804 (2.03) approximately equal to KU-2285 (2.30). The SER at a dose of 200 mg/kg and at an interval of 20 min (optimal interval) in the in vivo-in vitro colony assay increased as follows: PR-44 (1.26) approximately equal to PR-28 (1.29) < PR-69 (1.34) approximately equal to etanidazole (1.35) approximately equal to PR-350 (1.36) < RP-170 (1.41) approximately equal to PR-68 (1.41) < KU-2285 (1.49). The growth delay assay also showed that PR-350 was less efficient than KU-2285 and more efficient than PR-28. PR-350 and the four isomers had similar reduction potentials, but PR-28 and PR-44 were more hydrophilic than PR-68 and PR-69. The LD50 in mice were 5.8 g/kg for PR-350, approximately 7 g/kg for PR-28, 4 g/kg for PR-68, and 6 g/kg for PR-44 and PR-69. The concentration of PR-28 in the murine sciatic nerve was lower than that of PR-350. CONCLUSION: In vivo radiosensitizing activity differed among the four optical isomers, which appeared to be due, at least in part, to differences in lipophilicity. Although PR-28 was the least toxic, its low sensitization efficiency does not warrant clinical trials. Among the PR compounds, PR-68 appears to be most efficient, but optical resolution of PR-68 from PR-350 is expensive, and asymmetrical synthesis of PR-68 is not established. Therefore, PR-350 seems to be most suitable for further investigation among the PR-350 series compounds, considering its higher efficiency compared with PR-28 and PR-44, and established synthesis.

Animals↗

PubMed1995

Translocations and amplification of the BCL2 gene are detected in interphase nuclei of non-Hodgkin's lymphoma by in situ hybridization with yeast artificial chromosome clones.

Translocation of the BCL2 gene in B-cell malignancies carrying t(14;18) and amplification of the BCL2 gene in a cell line (HBL-2) derived from a non-Hodgkin's lymphoma (NHL) were detected specifically in both metaphase spreads and interphase nuclei by fluorescence in situ hybridization (FISH) using yeast artificial chromosomes (YACs). A YAC clone containing the BCL2 gene yA153A6, a 360-kb clone spanning from approximately 60 kb upstream of BCL2 exon 1 to approximately 60 kb 3' of the minor breakpoint cluster region, was used for single-color FISH analysis. Seven patients with NHL and one patient with acute lymphoblastic leukemia were analyzed for BCL2 translocations. Interphase nuclei of NHL patients showed three signals when hybridized with the yA153A6 probe. This was expected because the YAC clone spans the BCL2 breakpoint regions on 18q21.3. In a patient with acute lymphoblastic leukemia, a positive signal for BCL2 was detected on der(14) at band 14q32.33 by single-color FISH with the yA153A6 probe, whereas no signals were detected on der(18). The amplification of BCL2 in the HBL-2 cell line was observed on a characteristic abnormal chromosome 18, add(18)(q23); the periodic pattern of the fluorescent signal of this region was suggestive of an amplicon. Using double-color FISH with YAC clones containing the more centromeric 18q21.3 gene gastrin-releasing peptide (y302F10) and the 14q32.33 gene (IgH; Y6), we detected t(14;18) by showing the juxtaposition of the 18q21.3 and 14q32.33 bands on the derivative chromosome 18. Interphase FISH with these YAC clones provided a rapid procedure for the diagnosis of B-cell malignancies carrying t(14;18). In addition, we showed that translocations and amplification of the BCL2 gene can be detected at the single-cell level.

Adult↗

PubMed1995

Enhancement of beta-galactosidase gene expression in rat pheochromocytoma cells by exposure to extremely low frequency magnetic fields.

Exposure of PC12-VG cells to an extremely low frequency magnetic field (ELFMF) enhanced the beta-galactosidase gene expression stimulated by treatment of the cells with forskolin. The enhancing effect of the ELFMF was inhibited by treatment of the cells with a specific inhibitor of PKC, calphostin C, as well as with the Ca2+ entry blockers nifedipin and dantrolen. Enhancement appeared within the first hour of a 4h forskolin treatment when the ELFMF was given at different times during culture. We speculate that exposure of PC12-VG cells to an ELFMF during the early response to forskolin treatment affects cell signal transduction, resulting in enhanced gene expression.

Adrenal Gland Neoplasms↗

PubMed1995

Stereochemistry of the Aplysia neuronal 12-lipoxygenase: specific potentiation of FMRFamide action by 12(S)-HPETE.

Nervous tissue of the marine mollusc, Aplysia californica, generates arachidonic acid metabolites in response to neurotransmitters such as histamine or FMRFamide. In addition, identified neurons of Aplysia respond to the pharmacologic application of some of these products, particularly those of the 12-lipoxygenase pathway. We investigated the chirality of the initial Aplysia 12-lipoxygenase product, 12-HPETE, in preparation for more detailed metabolic studies and for the analysis of the physiological activity of the endogenous lipid. Neural homogenates and intact ganglia exclusively generate 12(S)-HPETE as do the better characterized mammalian lipoxygenases. The direct application of 12(S)-HPETE to cultured sensory neurons induced a hyperpolarization which averaged 2.6 mV. We did not find any difference between the response to the naturally-occurring 12(S)-HPETE and its diastereomer, 12(R)-HPETE which is not generated in Aplysia. Both isomers were significantly more effective than 15(S)-HPETE. In contrast, 12(S)-HPETE, but not 12(R)-HPETE, was a potent modulator of the action of the molluscan neuropeptide, FMRFamide. Prior application of 12(S)-HPETE to cultured sensory neurons increased the subsequent response to a submaximal dose of FMRFamide by 60%. On the other hand, 12(R)-HPETE reduced the subsequent response to the peptide by 30%. The lack of stereospecificity in the direct effect of the lipids differs markedly from their stereospecific effects as modulators of FMRFamide action. This suggests that there may be an important neurophysiologic role for these lipid modulators which is distinct from their direct effects, and also indicates that there are multiple sites and mechanisms by which lipid hydroperoxides act on neurons in Aplysia.

Animals↗

PubMed1995

Inhibition by interleukin-10 of inducible cyclooxygenase expression in lipopolysaccharide-stimulated monocytes: its underlying mechanism in comparison with interleukin-4.

Both interleukin-10 (IL-10) and IL-4 inhibited the prostanoid synthesis of lipopolysaccharide (LPS)-stimulated human monocytes, and their inhibition was shown to be based on a common mechanism to suppress the gene expression of inducible cyclooxygenase (COX). COX has been shown to exist in at least two distinct isoforms, designated COX-1 and COX-2, and their gene expressions exhibit different profiles. At both the protein and mRNA levels, the expression of COX-1 was constitutive and was not modulated by treatments with LPS, IL-10, or IL-4. In contrast, the expression of COX-2 was observed only after stimulation with LPS. IL-10 and IL-4 significantly inhibited LPS-induced COX-2 expression. Kinetic studies showed that they inhibited COX-2 mRNA expression within 1 hour after stimulation and that maximal inhibition was consistently observed at 5 hours. Moreover, the addition of cycloheximide (CHX) to LPS-stimulated monocytes resulted in a superinduction of COX-2 mRNA, whereas CHX almost abrogated the abilities of IL-10 and IL-4 to inhibit this gene expression. Experiments with actinomycin D showed that both cytokines accelerated the degradation of COX-2 mRNA. Furthermore, nuclear run-on experiments showed that both cytokines modestly inhibited LPS-induced COX-2 gene transcription. Thus, both cytokines seemed to regulate the COX-related pathway in a similar manner, although their receptor systems did not show any structural similarities. Considering recent findings showing that the drugs that exhibit a selective effect on COX-2 may be more preferable in inflammatory conditions, such biologic activities of IL-10 and IL-4 described above may offer useful tools in controlling inflammatory disorders in the future.

Cells, Cultured↗

PubMed1995

Interphase and metaphase detection of the breakpoint of 14q32 translocations in B-cell malignancies by double-color fluorescence in situ hybridization.

The breakpoint of 14q32 translocations found in B-cell malignancies was delineated specifically in both metaphase spreads and interphase nuclei by double-color fluorescence in situ hybridization (FISH) using bacteriophage clones containing the human immunoglobulin gamma chain gene locus (Ig gamma) and a cosmid clone, CY24-68, containing VH segments. CY24-68 is more telomeric than Ig gamma, separated by approximately 1 megabase (Mb). FISH studies were performed on four patients with non-Hodgkin's lymphoma (NHL), one with acute lymphoblastic leukemia (ALL), one with plasma cell leukemia (PCL), and three cell lines. In each patient with t(8;14), t(14;18), and t(3;14), the signal of Ig gamma gene was observed on der(14) and that of CY24-68 at respective partner sites of these translocations, 8q24.1, 18q21.3, and 3q27. Interphase nuclei with a signal of Ig gamma clearly separated from that of CY24-68 were more frequently encountered in all of the patients (45% to 74%) than those in normal controls (4% to 5%). Even in cases where only interphase nuclei were available for FISH studies, 14q32 translocations are detected as shown in two patients each with NHL and t(11;14)-carrying PCL. In two cell lines, HS-1 derived from ALL carrying t(8;14) and FR4 derived from a plasmacytoma carrying a complex form of t(8;14), the signal of Ig gamma was observed at the breakpoint region 8q24.1 of the der(8) in addition to the der(14), indicating that translocation event occurred within the Ig gamma locus. Intense Ig gamma signal was found at the breakpoint region on the der(14)t(11;14) in HBL-2 derived from NHL, indicating amplification of the Ig gamma gene, and presumably the resultant chimeric DNA between Ig gamma and DNA sequences at 11q13. The present approach allowed us to unequivocally detect tumor-specific breakpoints of 14q32 translocations. Furthermore, interphase FISH provides a rapid diagnostic procedure to detect 14q32 translocations in B-cell malignancies.

Burkitt Lymphoma↗