ABSTRACT
A 4-year-old boy with ALL received low-dose ara-C (50 mg/m2/day, bolus). After 10 fractions of ara-C, he developed an erythematous rash predominantly on the palms and soles, mimicking acral erythema except for the absence of pain. Chemotherapy was interrupted and the rash disappeared in four days. A similar rash occurred again just after the second cycle of ara-C had been started. Co-administration of dexamethasone improved the rash rapidly, thus allowing the chemotherapy to be continued, and suggesting the beneficial effect of corticosteroids. Although skin toxicity induced by low-dose ara-C is very rare and usually occurs after continuous infusion, it should also be borne in mind when considering bolus infusion.
Subject(s)
Antimetabolites, Antineoplastic/adverse effects , Cytarabine/adverse effects , Drug Eruptions/etiology , Antimetabolites, Antineoplastic/administration & dosage , Child, Preschool , Cytarabine/administration & dosage , Drug Eruptions/drug therapy , Humans , Male , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapyABSTRACT
BACKGROUND: It has been recently found that mice, especially males, with a disrupted angiotensin type 2 receptor (AT2R) gene, which is located on the X-chromosome, often have a range of congenital anomalies of the kidney and urinary tract (CAKUT), including renal hypoplasia, and that Caucasian male patients with ureteropelvic junction stenosis (UPJ) and multicystic dysplastic kidneys frequently have A-G transition in intron 1 of the AT2R gene. We have previously found that renal hypoplasia is remarkably predominant in Japanese boys. METHODS: We investigated sex ratios for the frequency of each CAKUT. The frequency of the A-G transition between the controls and 66 Japanese boys with CAKUT were compared. There was renal hypoplasia in 16, UPJ in 17, vesicoureteral in 20, and other anomalies in 13. We also investigated whether any mutations in AT2R genes were detectable in patients with renal hypoplasia. RESULTS: In contrast to mice with a disruption of the AT2R gene, the male-to-female ratios in human patients proved to be considerably variable: 16 for renal hypoplasia, 2.1 for UPJ, 0.8 for vesicoureteral, and 1.2 for others. The frequency of the A-G transition was not different between the control population and the patients with CAKUT [31 of 102 (30%) vs. 23 of 66 (35%), respectively]. A sequencing study disclosed no mutations in nine boys with renal hypoplasia. CONCLUSIONS: These findings indicate that the AT2R gene may not play a major role in the development of renal hypoplasia and other CAKUT in humans, at least in the Japanese population.
Subject(s)
Mutation , Receptors, Angiotensin/genetics , Urinary Tract/abnormalities , Alleles , Asian People/genetics , Base Sequence/genetics , Child , Female , Gene Frequency , Humans , Japan , Kidney/abnormalities , Male , Receptor, Angiotensin, Type 2 , Reference Values , Sex Characteristics , Urologic Diseases/geneticsABSTRACT
BACKGROUND: We studied the need for sling surgery in patients who suffered from large cystoceles and masked stress urinary incontinence. METHODS: Twenty patients who had large cystoceles but neither evidence nor history of stress incontinence were enrolled in this study. The cystocele was reduced using a reducing device. Masked urinary incontinence was identified by a 60 m pad weighing test and a stress test. The cystocele was reduced using a pessary ring in 14 patients, or a vaginal pack formed of two rolls of ordinary 28 x 28 cm gauze in six patients. Ten of 20 patients were diagnosed with masked stress urinary incontinence and were treated with anterior colporrhaphy and a suburethral sling procedure. The other 10 patients were continent after use of a cystocele reducing device and were treated with anterior colporrhaphy alone. Average follow-up periods of the patients with or without masked stress urinary incontinence were 51.2 months (range, 24.0-72.0 months) or 57.6 months (range, 27.0-70.0 months), respectively. RESULTS: One of the 10 patients diagnosed with masked stress incontinence had mild stress urinary incontinence postoperatively. None of the 10 continent patients had stress incontinence after anterior colporrhaphy alone. CONCLUSIONS: Reducing devices of protruding cystocele were clinically useful in the detection of masked stress incontinence. Sling surgery was effective to prevent emerging stress urinary incontinence for patients who suffered from cystocele and masked stress incontinence.
Subject(s)
Urinary Bladder Diseases/complications , Urinary Bladder Diseases/surgery , Urinary Incontinence, Stress/complications , Urinary Incontinence, Stress/surgery , Urologic Surgical Procedures , Aged , Female , Humans , Middle Aged , Pessaries , Treatment Outcome , Urinary Incontinence, Stress/diagnosis , Urologic Surgical Procedures/instrumentationABSTRACT
A 51-year-old woman was admitted with general fatigue, high fever and left upper abdominal pain. Abdominal computed tomography revealed a left adrenal mass, 15 cm in diameter with regular margins, the contents of which were not enhanced with contrast medium. The mass had heterogeneous echogenicity on the abdominal ultrasonograph. Serum hormonal levels were almost normal. Despite treatment with antibiotics, the high fever persisted. Based on these findings, the differential diagnosis was adrenal abscess or a nonfunctional adrenal tumor. Transabdominal left adrenalectomy was performed. Pathological examination revealed a hemorrhagic adrenal pseudocyst with infection. The patient's condition improved soon after the operation.
Subject(s)
Adrenal Gland Diseases/complications , Bacterial Infections/complications , Cysts/complications , Hemorrhage/complications , Adrenal Gland Diseases/diagnosis , Adrenal Gland Diseases/pathology , Adrenalectomy , Bacterial Infections/diagnosis , Bacterial Infections/pathology , Cysts/diagnosis , Cysts/pathology , Diagnosis, Differential , Female , Hemorrhage/diagnosis , Hemorrhage/pathology , Humans , Middle Aged , Treatment OutcomeABSTRACT
Sepsis is often associated with a downward spiral through a spectrum of systemic inflammatory response syndrome (SIRS) culminating in organ failure and death. Here we present a 3-year-old girl with Hemophilus influenzae septic meningitis who developed SIRS and acute renal failure. In the initial stage, the patient showed uremia, cytopenia, disseminated intravascular coagulation, elevation of tissue enzyme and ferritin values, hemophagocytosis and overproduction of nitric oxide. The serum cytokine profile revealed increased levels of soluble interleukin (IL)-2 receptor, IL-6, IL-10 and tumor necrosis factor alpha. The patient responded positively to early and intensive interventions including antibiotics, repeated exchange transfusions, dexamethasone and high-dose gamma-globulin. The above laboratory abnormalities almost normalized with clinical improvement. We consider that SIRS was probably responsible for the sequence of events resulting in renal failure in this case, and suggest that renal failure should be included among the serious complications of SIRS associated with Hemophilus influenzae septic meningitis.
Subject(s)
Acute Kidney Injury/complications , Meningitis, Haemophilus/complications , Systemic Inflammatory Response Syndrome/complications , Acute Kidney Injury/microbiology , Acute Kidney Injury/therapy , Child, Preschool , Female , Humans , Meningitis, Haemophilus/therapy , Systemic Inflammatory Response Syndrome/microbiology , Systemic Inflammatory Response Syndrome/therapyABSTRACT
A 5-year-old girl with a rare anomaly of a single system ectopic ureter draining into the mesonephric duct cyst and ipsilateral crossed fused kidney is presented. Both ureters were catheterized and three dimensional (3-D) images of the urinary tract were reconstructed with helical computed tomographic (CT) data. A mesonephric duct cyst, the right ureter draining into the cyst and an ectopic orifice were well depicted with these images, especially with inferior projection images. 3-D display of helical CT data with a retrograde contrast study is a promising method of obtaining anatomical detail of an ectopic ureter.
Subject(s)
Kidney/abnormalities , Ureter/abnormalities , Child, Preschool , Female , Humans , Kidney/diagnostic imaging , Kidney/surgery , Radiographic Image Enhancement , Radiographic Image Interpretation, Computer-Assisted , Tomography, X-Ray Computed/methods , Ureter/diagnostic imaging , Ureter/surgery , Urologic Surgical ProceduresABSTRACT
PURPOSE: There has not been an established method to distinguish initial lymphatics from blood capillaries under the light microscopy. In this study, we examined the usefulness of the immuno-histochemical staining method using a monoclonal anti-desmoplakin antibody in identifying initial lymphatics under the light microscopy. The specificity of this reaction was confirmed by the immuno-electron microscopy. MATERIAL AND METHODS: The cryostat sections of the human foreskin were observed under light microscopy by indirect immunoperoxidase method with the anti-desmoplakin mouse monoclonal antibody, and compared with the hematoxylin and eosin sections. These cryostat sections were also observed under electron microscopy by pre-embedding immunoperoxidase method with the same antibody. RESULTS: Under the light microscopy, the initial lymphatics of the human foreskin were visualized by the method with anti-desmoplakin antibody. These lymphatics were mainly distributed in the dermal layer, on the other hand, rarely seen in dermal papillae. Being usually found in closed shape, the lumens of initial lymphatics were hardly recognized as initial lymphatics by the ordinary hematoxylin and eosin staining. Under the immuno-transmission electron microscopy, the peroxidase-desmoplakin antibody precipitations were located on the surface of the endothelial cells of the vasculature which lacked pericytes and basal lamina, and was composed of endothelial cells alone. By these features of the vascular structures, the vessel reacting with anti-desmoplakin antibody was identified as initial lymphatics. CONCLUSION: This study shows the reliability and specificity of the immuno-histochemical method by anti-desmoplakin antibody in identifying initial lymphatics under light microscopy, and this method will be useful in studying the fine distribution of lymphatic vessels in normal human tissue.
Subject(s)
Lymphatic System/anatomy & histology , Penis , Skin , Animals , Antibodies, Monoclonal , Cytoskeletal Proteins/immunology , Desmoplakins , Humans , Immunohistochemistry/methods , Male , Mice , Microscopy, Immunoelectron , Reproducibility of ResultsABSTRACT
A 25-year-old woman was admitted to our hospital because of a painless, slow growing mass arising from the external genitalia. The mass had been developing for a few years. She did not have difficulty voiding nor was there hematuria. Magnetic resonance imaging revealed a well-circumscribed, 4 cm, solid tumor between the urethra and the anterior vaginal wall. After needle biopsy confirmed a benign tumor arising from the smooth muscle, the tumor was removed by a transvaginal approach. The histopathological diagnosis was epithelioid leiomyoma (leiomyoblastoma), which often occurs in the stomach or uterus, but seldom around the urethra. The patient has remained well without recurrence for 20 months after surgery.
Subject(s)
Leiomyoma, Epithelioid/pathology , Urethral Neoplasms/pathology , Adult , Female , Humans , Leiomyoma, Epithelioid/diagnosis , Leiomyoma, Epithelioid/surgery , Magnetic Resonance Imaging , Treatment Outcome , Urethral Neoplasms/diagnosis , Urethral Neoplasms/surgeryABSTRACT
PURPOSE: CD44 is an adhesion molecule expressed on a variety of cells, and its level correlates with the metastatic potential of malignant tumors. Serum concentrations of soluble CD44 (sCD44) are elevated in various cancers. The purpose of this study was to measure the serum concentrations of CD44 in pediatric patients with acute leukemia. PATIENTS AND METHODS: Fourteen pediatric patients with acute leukemia were studied. The authors measured the serum concentration of sCD44 by enzyme-linked immunosorbent assay before and after therapy. The concentrations were compared with those of 15 control healthy children and 10 patients with bacterial infections. RESULTS: The mean serum concentration of sCD44 at presentation was significantly higher in patients than in control subjects, but decreased to a normal range in complete remission after chemotherapy. There was no difference in sCD44 concentrations between patients with acute lymphocytic leukemia and those with acute myeloid leukemia. Serum concentrations of sCD44 did not correlate with lactic dehydrogenase concentrations or bone marrow nucleated cell counts and only weakly with peripheral leukocyte count. sCD44 levels in patients with bacterial infections were similar to those of control subjects. CONCLUSION: Serum concentration of sCD44 may reflect disease status in pediatric patients with acute leukemia and might be a useful tumor marker in these patients.
Subject(s)
Antigens, CD/blood , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Hyaluronan Receptors/blood , Leukemia, Myeloid, Acute/blood , Leukemia, Myeloid, Acute/drug therapy , Precursor Cell Lymphoblastic Leukemia-Lymphoma/blood , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Antibiotics, Antineoplastic/administration & dosage , Asparaginase/administration & dosage , Bacterial Infections/blood , Bacterial Infections/immunology , Biomarkers, Tumor/blood , Child , Child, Preschool , Cytarabine/administration & dosage , Enzyme-Linked Immunosorbent Assay , Humans , Infant , Leukemia, Myeloid, Acute/immunology , Methotrexate/administration & dosage , Precursor Cell Lymphoblastic Leukemia-Lymphoma/immunology , Prednisolone/administration & dosage , Reference Values , Remission Induction , Vincristine/administration & dosageABSTRACT
A 52-year-old Japanese woman was diagnosed as having angioimmunoblastic T-cell lymphoma (stage IV-B). She received 6 courses of chemotherapy including cyclophosphamide, doxorubicin, vincristine, and prednisolone every two weeks (biweekly CHOP), and was considered to be in partial remission. She complained of loss of visual acuity in her right eye during her last cycle of chemotherapy. Cytomegalovirus (CMV) retinitis was suspected from the characteristic ophthalmoscopic appearance. This diagnosis was further supported by the detection of CMV DNA in blood and antigens in polymorphonuclear leukocytes, a sign of CMV reactivation. Although DNAemia and antigenemia became negative, retinitis remained slightly active despite a 4-week systemic treatment of ganciclovir. Intraocular injection of ganciclovir was started and continued until the retinitis became inactive ophthalmoscopically. The patient received high-dose chemotherapy with peripheral blood stem cell transplantation and achieved complete remission. During the after this therapy no recurrence of CMV infections was observed. This case shows that 1) a quick and accurate diagnosis of CMV retinitis was possible by applying DNAemia and antigenemia and 2) intensive treatment for the CMV infection enabled the accomplishment of cure-oriented chemotherapy of the lymphoma without the recurrence of CMV retinitis.
Subject(s)
Cytomegalovirus Retinitis/complications , Cytomegalovirus Retinitis/drug therapy , Lymphoma/complications , Lymphoma/drug therapy , Female , Humans , Middle AgedABSTRACT
A fusion transcript of AF10 and CALM was isolated recently from the U937 cell line with t(10;11)(p13;q21). We performed reverse transcription-polymerase chain reaction and sequencing analysis on the t(10;11) leukemia samples obtained from four patients and one cell line, and we identified reciprocal fusion transcripts of AF10 and CALM in all the samples. The fusion transcripts in the five samples showed four different breakpoints in AF10 and three different breakpoints in CALM. In addition, the fusion transcripts in one sample showed a nucleotide sequence deletion in AF10, and those in two samples showed a nucleotide sequence deletion in CALM; the deletions were thought to be caused by alternative splicing. The variety of breakpoints and splice sites in the two genes resulted in five different-sized AF10-CALM mRNAs and in four different-sized CALM-AF10 mRNAs. Clinical features of 11 patients, including 6 of our own and 5 reported by others, in whom the fusion of AF10 and CALM was identified, are characterized by young age of the patients, mixed-lineage immunophenotype with coexpression of T-cell and myeloid antigens, frequent occurrence of a mediastinal mass, and poor clinical outcome.
Subject(s)
Chromosomes, Human, Pair 10/genetics , Chromosomes, Human, Pair 11/genetics , Leukemia, Biphenotypic, Acute/genetics , Leukemia, Biphenotypic, Acute/pathology , Oncogene Proteins, Fusion/genetics , RNA, Messenger/analysis , Adolescent , Adult , Child , Female , Humans , Immunohistochemistry , Immunophenotyping , In Situ Hybridization, Fluorescence , Karyotyping , Leukemia, Biphenotypic, Acute/diagnosis , Male , Middle Aged , RNA, Neoplasm/analysis , Sequence Analysis, DNA , Translocation, Genetic/geneticsABSTRACT
A case of aggressive angiomyxoma occurring in the scrotum is reported. A 57-year-old Japanese man presented with a 2-year history of non-tender soft mass in the scrotum. Computed tomography and magnetic resonance imaging revealed a well-defined mass 8 cm in diameter extending from the medial aspect of the left ischium. Angiography revealed faint vascularity fed by the left internal pudendal artery. Excision was performed by a scrotal approach, and histological examination confirmed an aggressive angiomyxoma. The patient showed no recurrence at 3 months follow-up.
Subject(s)
Genital Neoplasms, Male/diagnosis , Myxoma/diagnosis , Scrotum , Female , Follow-Up Studies , Genital Neoplasms, Male/pathology , Genital Neoplasms, Male/surgery , Humans , Male , Middle Aged , Myxoma/pathology , Myxoma/surgery , Treatment OutcomeABSTRACT
The familial form of hemophagocytic lymphohistiocytosis (HLH) is a lethal disorder. Although the prognosis for Epstein-Barr virus-associated HLH (EBV-HLH) remains uncertain, numerous reports indicate that it can also be fatal in a substantial proportion of cases. We therefore assessed the potential of immunochemotherapy with a core combination of steroids and etoposide to control EBV-HLH in 17 infants and children who met stringent diagnostic criteria for this reactive disorder of the mononuclear phagocyte system. Treatment of life-threatening emergencies was left to the discretion of participating investigators and typically included either intravenous Ig or cyclosporin A (CSA). Five patients (29%) entered complete remission during the induction phase (1 to 2 months), whereas 10 others (57%) required additional treatment to achieve this status. In 2 cases, immunochemotherapy was ineffective, prompting allogeneic bone marrow transplantation. Severe but reversible myelosuppression was a common finding; adverse late sequelae were limited to epileptic activity in one child and chronic EBV infection in 2 others. Fourteen of the 17 patients treated with immunochemotherapy have maintained their complete responses for 4+ to 39+ months (median, 15+ months), suggesting a low probability of disease recurrence. These results provide a new perspective on EBV-HLH, showing effective control (and perhaps cure) of the majority of EBV-HLH cases without bone marrow transplantation, using steroids and etoposide, with or without immunomodulatory agents.
Subject(s)
Epstein-Barr Virus Infections , Etoposide/therapeutic use , Histiocytosis, Non-Langerhans-Cell/therapy , Histiocytosis, Non-Langerhans-Cell/virology , Immunoglobulins, Intravenous/therapeutic use , Steroids/therapeutic use , Child , Child, Preschool , Cyclosporine/therapeutic use , DNA, Viral/analysis , Dexamethasone/therapeutic use , Female , Glucocorticoids/therapeutic use , Herpesvirus 4, Human/genetics , Humans , Immunosuppressive Agents/therapeutic use , Infant , Male , Prednisolone/therapeutic use , Remission InductionABSTRACT
PURPOSE: Essential thrombocythemia and agnogenic myeloid metaplasia as one form of idiopathic myelofibrosis are myeloproliferative disorders and are quite rare in children. A patient with essential thrombocythemia that transformed to "adult-type" agnogenic myeloid metaplasia is described. PATIENTS AND METHODS: A routine examination of an 8-year-old girl with bronchial asthma showed thrombocytosis. Essential thrombocythemia was diagnosed 2 years later. During a 3-year follow-up without treatment, transition of the essential thrombocythemia to agnogenic myeloid metaplasia was noticed. The patient had an excellent response to interferon (IFN)-alpha therapy. CONCLUSION: This case is unique because of the availability of premorbid hematologic data and the natural progression of essential thrombocythemia to agnogenic myeloid metaplasia. Whether IFN-alpha therapy can prevent the progression of idiopathic myelofibrosis to leukemia has not yet been determined.
Subject(s)
Interferon-alpha/therapeutic use , Primary Myelofibrosis/drug therapy , Primary Myelofibrosis/etiology , Thrombocytosis/complications , Child , Female , Humans , Thrombocytosis/physiopathologyABSTRACT
Brain metastasis from prostate cancer is a rare clinical event. We present a case of prostate cancer with a solitary brain metastasis as a sole site of recurrence after total prostatectomy. To our knowledge, this is the third reported case of an isolated brain metastasis from prostate cancer.
Subject(s)
Adenocarcinoma/secondary , Brain Neoplasms/secondary , Prostatectomy , Prostatic Neoplasms/pathology , Adenocarcinoma/diagnosis , Adenocarcinoma/surgery , Brain Neoplasms/diagnosis , Brain Neoplasms/surgery , Craniotomy , Follow-Up Studies , Humans , Male , Middle Aged , Neoplasm Recurrence, Local , Prostate-Specific Antigen/blood , Prostatic Neoplasms/blood , Prostatic Neoplasms/surgery , Tomography, X-Ray ComputedABSTRACT
A case of giant testicular tumor associated with scrotal gangrene is reported. A 33-year-old man had a swollen scrotum (15 cm) accompanied with necrosis and a foulodor. The tumor had invaded the scrotum, perineum and the left spermatic cord. Serum alpha-fetoprotein level was 15,487 ng/ml. The chest radiograph revealed multiple metastases. Bilateral high orchiectomies and local resection with a wide margin were performed. The tumor weighed 2.5 kg and the histopathological diagnosis was teratocarcinoma. He was treated with 3 courses of chemotherapy with cisplatin, etoposide and peplomycin. A second-look surgery revealed no viable cancer cells in the residual masses. The patient has been free of recurrence 4 months postoperatively.
Subject(s)
Genital Diseases, Male/complications , Scrotum/pathology , Teratocarcinoma/complications , Testicular Neoplasms/complications , Adult , Gangrene , Genital Diseases, Male/pathology , Humans , Male , Neoplasm Invasiveness , Neoplasm Metastasis , Teratocarcinoma/secondary , Testicular Neoplasms/pathologyABSTRACT
A 31-year-old man was admitted to our hospital with the chief complaint of painful right scrotal swelling. Based on the diagnosis of right testicular tumor with multiple lung metastasis and L2 vertebral body metastasis, right high orchiectomy and three courses of chemotherapy (peplomycin, etoposide, CDDP) were performed. Histological diagnosis was teratocarcinoma. With the complete remission for lung metastasis and no change for bone metastasis, L2 spondylectomy and additional four courses of the same chemotherapy were performed. The patient has been free of the disease for 11 months after the spondylectomy.
Subject(s)
Lumbar Vertebrae , Spinal Neoplasms/secondary , Spinal Neoplasms/surgery , Teratocarcinoma/secondary , Testicular Neoplasms/pathology , Adult , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Cisplatin/administration & dosage , Combined Modality Therapy , Disease-Free Survival , Etoposide/administration & dosage , Humans , Lumbar Vertebrae/surgery , Lung Neoplasms/secondary , Lung Neoplasms/therapy , Male , Orchiectomy , Peplomycin/administration & dosage , Teratocarcinoma/pathology , Teratocarcinoma/surgery , Testicular Neoplasms/surgeryABSTRACT
A 52-year-old man presented with a painful, gradually enlarging mass in the left inguinal region. An ultrasound examination demonstrated a lobulated, heterogenous tumor 6.0 x 4.0 x 3.0 cm in diameter, which separated from the left testis and epididymis. Radical inguinal orchiectomy with wide en bloc local resection was performed. Histologic diagnosis was a malignant fibrous histiocytoma (MFH) with a giant cell variant. The patient underwent postoperative regional irradiation and has been alive without metastasis and local recurrence 3 months after the operation. Among the 19 patients with MFH of spermatic cord reported in Japan, only two cases were of giant cell type of MFH including the present case.
Subject(s)
Genital Neoplasms, Male/surgery , Histiocytoma, Benign Fibrous/surgery , Spermatic Cord , Humans , Male , Middle AgedABSTRACT
The acute effect of RNA and DNA synthesis inhibitors on DNA topoisomerase (topo) I localization within cells was examined. Indirect immunofluorescence revealed that topo I was distributed throughout the nuclei but was concentrated in nucleoli of untreated K562 leukemia cells and A549 non-small cell lung cancer cells. Treatment with the DNA polymerase inhibitor aphidicolin did not alter this distribution. In contrast, 30-60 min after addition of the RNA synthesis inhibitor 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole (DRB) at concentrations that inhibited [3H]uridine incorporation into RNA by > or = 50%, topo I was visible throughout the nuclei without nucleolar accentuation. Western blotting and activity assays confirmed that the amount of topo I polypeptide and topo I activity were unaltered by the brief DRB treatment. Within 30 min of DRB removal, topo I relocalized to the nucleoli in the absence or presence of the protein synthesis inhibitor cycloheximide. Collectively, these results suggest a reversible translocation of topo I out of the nucleoli when RNA synthesis is inhibited. Treatment with the topo I poisons topotecan or camptothecin, agents that also inhibit RNA synthesis, likewise caused redistribution of topo I to nonnucleolar regions of the nucleus in a variety of cell types. In DC3F hamster lung fibroblasts, 2.5 microM topotecan or 1.25 microM camptothecin was sufficient to cause this topo I redistribution. In DC3F/C-10 cells that contain a mutant camptothecin-resistant topo I, topo I relocalization required 50-fold higher concentrations of topotecan or camptothecin but not DRB. These observations not only suggest that accumulation of topo I in the nucleolus is related to ongoing RNA synthesis but also raise the possibility of screening for some types of camptothecin resistance at the single-cell level using a rapid immunofluorescence-based assay.
Subject(s)
DNA Topoisomerases, Type I/metabolism , Dichlororibofuranosylbenzimidazole/pharmacology , RNA/biosynthesis , Animals , Camptothecin/analogs & derivatives , Camptothecin/pharmacology , Cell Nucleus/enzymology , Cricetinae , Humans , Mice , Topotecan , Tumor Cells, CulturedABSTRACT
We report a 3-year-old boy with acute myelogenous leukemia, who relapsed very early after peripheral blood stem cell transplantation (PBSCT). He was admitted with a tumor in maxillar sinus and hemorrhagic diathesis and was diagnosed as having acute myelogenous leukemia with t(8;21). He achieved complete remission with etoposide, cytosine arabinoside and mitoxantrone. After 8 courses of consolidation therapy and marrow ablative chemotherapy, he received PBSCT. G-CSF was given from day 0 because of severe infection. WBC and platelete counts rapidly increased, however, from day 20 platelet count spontaneously decreased. Concomitantly bone marrow examination revealed the presence of blastic cells. RT-PCR showed that the presence of AML 1/MTG 8 chimera mRNA in the cryopreserved PBSC samples. In vitro analysis also revealed that leukemic cells had G-CSF receptors and increased 3H-thymidine uptake in the presence of G-CSF. These findings strongly suggest that the reinfusion of leukemic cells in PBSC and the administration of G-CSF after PBSCT might be relevant to early relapse in this patient.