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Biomedical subjects

T Soma

Publications and source records attributed to T Soma.

At least 55 records · Page 3Linked to original sources
PubMed1998

Analysis of apoptotic cell death in human hair follicles in vivo and in vitro.

We analyzed changes of growth and apoptotic cell death in human hair follicles. In anagen hair follicles, terminal deoxynucleotidyltransferase-mediated deoxyuridine triphosphate-biotin nick labeling-positive cells were observed in the keratogenous zone of the upper bulb matrix, the inner root sheath, and the companion layer of the outer root sheath. DNA ladder formation was also detected in anagen hair follicles. In catagen hair follicles, the lower bulb matrix cells around the dermal papilla and the outer layer cells of the outer root sheath became strongly positive, showing that apoptosis in catagen hair is distinct from that in anagen hair. We also confirmed the mRNA expression of four caspases (caspase-1, caspase-3, caspase-4, and caspase-7) in anagen hair follicles by reverse transcriptase-polymerase chain reaction and in situ hybridization. When human anagen hair follicles were cultured in the presence of transforming growth factor-beta or tumor necrosis factor-alpha in the serum-free medium, transforming growth factor-beta but not tumor necrosis factor-alpha induced catagen-like morphologic changes, which were indistinguishable from normal catagen hair follicles. Tumor necrosis factor-alpha, however, strongly inhibited the elongation of the hair shaft in a dose-dependent manner, accompanied by abnormal morphology and increased cell death in the bulb matrix cells. Our results suggest that apoptosis in hair follicles involves two different types. One is related to the terminal differentiation of follicular epithelial cells in anagen hair. The other occurs as a major driving force to eliminate the distinct portion of epithelial components in catagen hair. Furthermore, this study strongly indicates that the transforming growth factor-beta pathway is involved in the induction of catagen phase in human hair cycle.

Antibodies↗
PubMed1998

High incidence of chemotherapy-induced acral erythema in female patients with non-Hodgkin's lymphoma treated with the VACOP-B regimen.

Seven patients, all females out of 29 with non-Hodgkin's lymphoma (NHL) (16 males and 13 females) treated with the VACOP-B regimen utilizing granulocyte-colony-stimulating factor (G-CSF) support developed chemotherapy-induced acral erythema (CAE). In contrast, none of 32 patients with NHL who were treated with CHOP, MACOP-B, or biweekly CHOP regimens without G-CSF developed CAE. Total dose intensities of VACOP-B regimen were higher than those of the three other regimens. However, no significant difference in dose intensities of each drug in the patients treated with the VACOP-B regimen was found between male and female patients and between female patients with or without CAE. The cause of the high incidence of CAE (7/13) in the female patients treated with VACOP-B regimen remains unknown. However, female sex hormones may increase susceptibility to CAE. Since the occurrence of CAE interrupts intensive chemotherapy and reduces the cure rate, high risk patients for CAE should be carefully monitored for early symptoms and signs of CAE and should be treated early and appropriately.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1998

[Familial pulmonary arteriovenous malformation diagnostic of the Osler-Weber-Rendu disease].

A 53-year-old woman was admitted to the hospital for investigation of an abnormal shadow in the middle lobe of the right lung on a chest X-ray film. The filling of most of the shadowed area with contrast media on a chest CT scan suggested a vascular lesion. Further investigation by intravenous digital subtraction angiography and color doppler sonography led to the diagnosis of pulmonary arteriovenous malformation. An abdominal CT scan suggested the presence of an arteriovenous malformation in the liver, and a bronchoscopic study revealed telangiectatic lesions on the laryngeal mucosa. The patient's father had died at the age of 61, due to intracranial bleeding, which suggested he might have had an arteriovenous malformation in the brain. The patient's daughter has a pulmonary arteriovenous malformation. This family of vascular malformation indicates that the patient had Osler-Weber-Rendu disease. Osler-Weber-Rendu disease is an autosomal-dominant inherited disorder that may give rise to arteriovenous malformations, mainly in the lungs and the brain. We found that color doppler sonography can be useful for the diagnosis of pleural-based pulmonary arteriovenous malformation.

Adult↗
PubMed1997

Aberrant overexpression of the Wilms tumor gene (WT1) in human leukemia.

To clarify whether the expression of the WT1 gene in leukemic cells is aberrant or merely reflects that in normal counterparts, the expression levels of the WT1 gene were quantitated for normal hematopoietic progenitor cells. Bone marrow (BM) and umbilical cord blood (CB) cells were fluorescence-activated cell sorting (FACS)-sorted into CD34+ and CD34- cell populations, and the CD34+ cells into nine subsets (CD34+ CD33-, CD34+ CD33+, CD34+ CD38-, CD34+ CD38+, CD34+ HLA-DR-, CD34+ HLA-DR+, CD34+ c-kit(high), CD34+ c-kit(low), and CD34+ c-kit-) according to the expression levels of CD34, CD33, CD38, HLA-DR, and c-kit. Moreover, acute myeloid leukemic cells were also FACS-sorted into four populations (CD34+ CD33-, CD34+ CD33+, CD34- CD33+, and CD34- CD33-). FACS-sorted normal hematopoietic progenitor and leukemic cells and FACS-unsorted leukemic cells were examined for the WT1 expression by quantitative reverse transcriptase-polymerase chain reaction. The WT1 expression in the CD34+ and CD34- cell populations and in the nine CD34+ subsets of BM and CB was at either very low (1.0 to 2.4 x 10(-2)) or undetectable (< 10(-2)) levels (the WT1 expression level of K562 cells was defined as 1.0), whereas the average levels of WT1 expression in FACS-sorted and -unsorted leukemic cells were 2.4 to 9.3 x 10(-1). Thus, the WT1 expression levels in normal hematopoietic progenitor cells were at least 10 times less than those in leukemic cells. Therefore, we could not find any normal counterparts of BM or CB that expressed the WT1 at levels comparable with those in leukemic cells. These results indicate an aberrant overexpression of the WT1 gene in leukemic cells and imply the involvement of this gene in human leukemogenesis.

Acute Disease↗
PubMed1997

Lineage- and differentiation stage-specific expression of LSM-1 (LPAP), a possible substrate for CD45, in human hematopoietic cells.

CD45, a transmembrane tyrosine phosphatase, is found on almost all nucleated hematopoietic cells and plays a crucial role in lymphocyte activation and differentiation. We recently achieved isolation of the human LSM-1 (hLSM-1) gene, whose product is a possible substrate for CD45, and we raised antibodies against the hLSM-1 protein. hLSM-1 expression in hematopoietic cells was examined with Northern and Western blot, fluorescence-activated cell sorter, and immunocytochemical analyses. It was found that in the lymphoid lineage, T and B lymphocytes as well as NK cells expressed LSM-1, whereas terminally differentiated plasma cells did not. As for the myeloid lineage, immature myeloid cells expressed LSM-1, whereas terminally differentiated granulocytes and monocytes did not. In the erythroid lineage, normal erythroblasts expressed very low levels of LSM-1, while erythroid cell lines (K562 and HEL) did not. Megakaryocytes did not express LSM-1. Both CD34+/CD33- and CD34+/CD33+ hematopoietic progenitor cells weakly expressed LSM-1. These results showed that LSM-1 is expressed in a lineage- and differentiation stage-specific fashion.

Blotting, Western↗
PubMed1997

Transduction of hematopoietic stem cells in humans and in nonhuman primates.

Primitive hematopoietic progenitor and stem cells have been pursued as highly desirable targets for genetic therapy. Retroviral vectors have been used for the majority of preclinical and clinical studies directed at these cells; however, both preclinical and early clinical studies indicate that the gene transfer efficiency of the current generation of vectors using known transduction conditions into primate and human repopulating stem cells is too low to be of clinical utility in most situations. In this presentation I will summarize the status of our completed and ongoing clinical genetic marking trials, and describe our efforts in the laboratory and use of primate transplantation models to improve on these results.

Animals↗
PubMed1997

Prednisolone therapy for intra-abdominal desmoid tumors in a patient with familial adenomatous polyposis.

The management of intra-abdominal desmoid tumors in patients with familial adenomatous polyposis (FAP) is very difficult. Non-steroidal anti-inflammatory drugs (NSAIDs), anti-estrogenic agents, and steroids are most commonly used, because surgical removal of these tumors may result in severe morbidity, with local recurrence being common. We report a patient with FAP and intra-abdominal desmoid tumors that regressed markedly after prednisolone therapy. The patient, a 38-year-old woman, had undergone total colectomy and ileorectal anastomosis with a diagnosis of FAP with colon cancer. Approximately 17 months after the surgery, she noticed an elastic firm lump in the abdominal wall. She also experienced lower abdominal distension. Computed tomography (CT) of the lower abdomen showed an invasive heterogenous low-density mass occupying the intra-abdominal space. She was treated with sulindac, NSAID, at 300 mg/day, the diagnosis being intra-abdominal desmoid tumors. She exhibited an intestinal obstruction about 9 months after the initiation of sulindac therapy. We changed the treatment and began prednisolone (initial dose, 40 mg/day). This treatment was continued for two years; subsequently, the lesions regressed markedly. She is currently well, more than 3 years after the withdrawal of prednisolone.

Adenomatous Polyposis Coli↗
PubMed1997

Murine long-term repopulating ability is compromised by ex vivo culture in serum-free medium despite preservation of committed progenitors.

Hematopoietic progenitor cells can be maintained and expanded ex vivo in standard or serum-free culture medium supplemented with a variety of stimulatory cytokines. The use of serum-free medium allows specification of reproducible and precise growth conditions optimal for various applications and is more acceptable from a safety and regulatory point of view. Human and murine committed progenitor cells have been shown to be equivalently ro better supported by serum-free culture conditions in the presence of multicytokine combinations, but there is little information on the effects of such culture conditions on repopulating stem cells. We used a murine competitive repopulation model to assess the effect of serum-free versus serum-containing ex vivo culture on long-term reconstituting cells. Despite equivalent numbers of committed CFU-C and day 12 CFU-S present after 4 days of culture of murine marrow in serum-free or serum-containing conditions in the presence of IL-3, IL-6, and SCF, long-term reconstituting activity was significantly impaired by serum-free culture. These findings may have important implications for transplantation and gene therapy applications.

Animals↗
PubMed1997

Hepatoid carcinoma of the lung with production of alpha-fetoprotein and abnormal prothrombin: an autopsy case report.

Alpha-fetoprotein (AFP) is a useful tumor marker for the diagnosis of hepatic and testicular tumors. Several cases of AFP-producing lung cancer have been reported. We present here a patient with AFP-producing primary lung carcinoma, which showed high values of serum AFP (100,000 ng/mL). The concanavalin A nonbinding fraction rate of AFP was 15%. Gross and microscopic features of the lung carcinoma bore a striking resemblance to those of hepatocellular carcinoma. According to the histologic classification of lung tumor, this case was large cell carcinoma with prominent hepatoid differentiation. Immunohistochemically, we detected AFP in the cytoplasm of the neoplastic cells. We also detected another useful tumor marker for the diagnosis of hepatocellular carcinoma, i.e., des-gamma-carboxy prothrombin (protein induced by vitamin K absence or the absence of antagonist-II [PIVKA-II]), in serum using an enzyme immunoassay and in tumor cells by immunohistochemical analysis.

Biomarkers↗
PubMed1996

Long-term follow-up of minimal residual disease in leukemia patients by monitoring WT1 (Wilms tumor gene) expression levels.

Thirty-one patients (27 with acute myeloid leukemia [AML], 2 with acute lymphocytic leukemia [ALL], and 2 with acute mixed lineage leukemia [AMLL]) treated with conventional chemotherapy (CHT) and 23 patients (13 AML, 5 ALL, and 5 with chronic myeloid leukemia [CML]) treated with allogeneic bone marrow transplantation (BMT) were monitored for WT1 expression levels in BM and peripheral blood (PB) by reverse transcriptase-polymerase chain reaction over a long-term period (mean, 29 months for CHT and 24 months for BMT). Sixteen of the patients in the CHT group and 3 in the BMT group who had achieved complete remission suffered clinical relapse. In 10 of these patients, WT1 expression that had returned to normal BM levels (< 10(-3); the WT1 expression level of K562 cells was defined as 1.0) after complete remission (CR) either gradually or rapidly increased again to abnormal levels 1 to 18 months (mean, 7 months) before clinical relapse became apparent. In another 9 patients, WT1 expression never returned to normal BM levels even after CR and the subsequent relapse was accompanied by a rapid increase in WT1 expression to levels higher than 10(-2) (10(-3) levels in PB). On the other hand, the remaining 35 patients (15 CHT and 20 BMT) maintained their CR. In 29 of these patients (11 CHT and 18 BMT), WT1 expression either gradually or rapidly decreased to normal BM levels, whereas in the other 6 (4 CHT and 2 BMT), low or very low levels of WT1 mRNAs (10(-3) to 10(-2) in BM and 10(-5) to 10(-3) in PB) remain detectable, but without any clinical signs of relapse. A clear correlation was found to exist between the minimal residual disease (MRD) detected in the paired BM and PB samples for all types of leukemias (AML, ALL, and CML), with MRD in PB being approximately one-tenth of that in BM. WT1 quantitation of 168 paired BM and PB samples showed that PB samples were superior to BM samples for the detection of MRD. We conclude that monitoring of WT1 expression levels in BM and PB makes it possible to rapidly assess the effectiveness of individual treatment and diagnose clinical relapse in the early stage for all leukemia patients regardless of the presence or absence of tumor-specific DNA markers.

Bone Marrow↗
PubMed1996

Maintenance of murine long-term repopulating stem cells in ex vivo culture is affected by modulation of transforming growth factor-beta but not macrophage inflammatory protein-1 alpha activities.

Transforming growth factor-beta (TGF-beta) and macrophage inflammatory protein-l alpha (MIP-1 alpha) are both well-described inhibitors of committed and multipotential hematopoietic progenitors. The effect of these cytokines; on true stem cell activity in ex vivo culture systems as assayed by murine long-term repopulating activity (LTRA) has not been examined. We studied the stem cell effects of the addition of these cytokines to ex vivo cultures containing interleukin-3 (IL-3), IL-6, and stem cell factor (SCF), using the murine competitive repopulation assay. We also tested the impact of adding an anti-TGF-beta neutralizing antibody, to ask whether abrogation of autocrine/paracrine TGF-beta may protect or enhance the survival of LTRA during ex vivo culture. TGF-beta 1 had significant suppressive effects on both short- and long-term repopulating activities, and anti-TGF-beta antibody had enhancing effects compared with control cultures containing IL-3, IL-6, and SCF alone. MIP-1 alpha had no significant effects on either short- or long-term repopulating ability. These data suggest that abrogation of TGF-beta during suspension culture may allow enhanced survival or even expansion of primitive cells ex vivo, with implications for many applications, including gene therapy.

Animals↗
PubMed1996

Differentiation of vaccine virus from field isolates of feline panleukopenia virus by polymerase chain reaction and restriction fragment length polymorphism analysis.

In an attempt to distinguish feline panleukopenia virus (FPLV) live vaccine strains from FPLV field isolates in Japan, we compared restriction fragment length polymorphisms (RFLP) of polymerase chain reaction (PCR)-amplified fragments of live FPLV vaccine strains with those of FPLV Japanese field isolates. On the basis of nucleotide sequence differences between PLI-IV, a live vaccine strain, and FPV-483, a recent field isolate, two restriction enzymes, Dra I and Afa I, were selected for PCR-RFLP analysis of nucleotide (nt) differences at nt 3695 and 4508, respectively. Three live vaccine strains including the PLI-IV strain could be distinguished from the Japanese field isolates by their PCR-RFLP patterns by Afa I, but one live vaccine strain was indistinguishable from the Japanese isolates when Dra I and Afa I were used. The Japanese field isolates were divided into two groups by the profile of PCR-RFLP patterns generated by Dra I and Afa I, suggesting that PCR-RFLP analysis using several enzymes provides a good genetic estimate of strain differentiation. No isolate that shows a Dra I-negative/Afa I-negative pattern has emerged in Japan, indicating the possibility that the live vaccine viruses with a Dra I-negative/Afa I-negative pattern, such as the PLI-Iv strain, are candidates for use as live FPLV vaccine strain in Japan where they can be genetically distinguished from field strains.

Animals↗
PubMed1996

The expression of IL-6 and its related genes in acute leukemia.

Acute myeloid leukemia (AML) blast cells frequently produce interleukin-6 (IL-6) and other cytokines such as colony-stimulating factors (CSF: G-CSF, M-CSF, and GM-CSF), tumor necrosis factor (TNF)-alpha, and IL-1. The AML blast cells that produced IL-6 alone could not form autonomous in vitro colonies, whereas the blast cells that coexpressed CSF in addition to IL-6 were able to form such colonies. This suggests that IL-6 acts as a costimulator to enhance CSF-induced clonogenicity of AML blast cells. TNF-alpha and IL-1 that are produced from the blast cells may stimulate the growth of the AML blast cells by inducing production of CSF in bone marrow stromal cells or in the blast cell population itself. Improvement of clinical manifestations by the administration of an anti-IL-6 murine monoclonal antibody in a patient with AML-M5B confirmed an important role of IL-6 in in-vivo growth of the blast cells. The mRNA expression of IL-6 and its related genes in AML and acute lymphoid leukemia (ALL) blast cells was analyzed by reverse transcriptase-polymerase chain reaction (RT-PCR). IL-6 mRNA expression was common in AML, but rare in ALL, whereas the IL-6 receptor (IL-6R) mRNA was expressed in almost all cases of AML and in more than half of the cases of ALL. In contrast, gp130 was ubiquitously expressed in both AML and ALL. A significant correlation between the levels of IL-6R expression and the responsiveness of the blast cells to exogenous IL-6 was observed. This suggests the possibility of the rapid prediction of the responsiveness of leukemic cells to exogenous IL-6 (IL-6 administration for therapy) by rapid measurement of IL-6R mRNA by RT-PCR.

Acute Disease↗
PubMed1996

[Comparison between intermittent retrograde cold blood cardioplegia and retrograde crystalloid cardioplegia].

Intermittent retrograde cold blood cardioplegia was compared with retrograde crystalloid cardioplegia. Twenty-two adult patients underwent open heart surgery divided into two groups. Group BCP (n = 10) was protected with 15 degrees C blood containing potassium 15 mEq/l; Group CCP (n = 12) was protected with 4 degrees C St. Thomas' Hospital cardioplegic solution. Lactate, pyruvate, and CK-MB levels in coronary sinus blood were measured at 5 and 15 minutes after aortic unclamping and 5 minutes after weaning from cardiopulmonary bypass (CPB) in both groups. CPB time, cross-cross clamp time, incidence of postoperative low output syndrome and spontaneous return to sinus rhythm after aortic unclamping were not different between two groups. Cardiac index and pulmonary capillary wedge pressure measured immediately after weaning from CPB, were not different in both groups. Lactate level was significantly low in group BCP. Lactate uptaking ratio of myocardium was significantly high in group BCP. CK-MB levels were not different between two groups. Cold blood cardioplegia was seemed to provide better aerobic myocardial metabolism during aortic cross clamp. However, CK-MB levels and hemodynamic studies were not different.

Aged↗
PubMed1995

Diverticular disease of the colon at a regional general hospital in Japan.

PURPOSE: X-ray film registry records were reviewed to better understand the changing nature of diverticular disease (DD) of the colon in Japan. RESULTS: Among 6,849 patients undergoing barium enema examination during a eight-year period from 1985 to 1992, this condition was found in 1,074 patients (15.7 percent), including 702 males (65.4 percent) and 372 females (34.6 percent). During this eight-year period there was an increase in frequency from 10.7 percent in 1985 to 17.8 percent in 1992. The proportion of patients with right-sided, bilateral, and left-sided DD was 69.2 percent, 17.5 percent, and 13.3 percent, respectively. The right-sided DD was more common in the younger age group and was predominant in male patients, whereas the left-sided DD increased with age, especially in female patients. Of the 1,074 patients, 11 (1.0 percent) underwent surgery in the same period. Regarding the right-sided DD, only 2 of 743 patients received surgery (0.3 percent). On the other hand, of the 143 patients with left-sided DD, 9 patients (6.3 percent) received some form of surgery. CONCLUSION: Right-sided diverticular disease of the colon is still common in Japan. It does not appear that this tendency will change in the future. Nearly all patients diagnosed as having diverticula had either no symptoms or only mild symptoms, and only about 1 percent required surgery. Right-sided diverticular disease of the colon seems to have had no serious clinical problems compared with left-sided DD.

Adolescent↗
PubMed1995

Adjuvant-induced persistent photosensitivity models in guinea pigs. I. Induction of persistent photosensitivity.

Induction of persistent photosensitivity in guinea pigs was carried out in an attempt to induce a model suitable to clarify the mechanism of human persistent light reactors. Guinea pigs were treated with intradermal injection of adjuvant which consisted of desiccated Mycobacteria followed by topical application of hapten solution and irradiation with UVA. Unequivocal skin reactions were subsequently elicited with UVA exposure in the absence of hapten application. This enhanced UVA reactivity persisted and could be elicited for more than 2 years. In these guinea pigs, remarkably increased sensitivity to UVB was also observed. These animals appear quite similar to persistent light reactors among humans. Muramyl dipeptide used in place of Mycobacteria was also found to be effective in inducing photosensitivity to UVA. There were great differences of reactivity noted among different strains of guinea pig, suggesting that persistent photosensitivity is influenced by genetic background. Enhanced UV sensitivity was induced without hapten application, only with injections of adjuvant and UVA irradiation in the immunization procedure. These results suggest that this model will be useful to study chronic actinic dermatitis.

Acetylmuramyl-Alanyl-Isoglutamine↗