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Biomedical subjects

Y Kohgo

Publications and source records attributed to Y Kohgo.

At least 163 records · Page 9Linked to original sources
PubMed1993

[Follicular lymphoma associated with t(14;18)(q32;q21) chromosome translocation and bcl-2 gene rearrangement: report of a case].

A 31-year-old Japanese male who complained of low-grade fever, fatigue and generalized lymphadenopathy had shown an increase in peripheral white cell count, and 84% of peripheral blood cell and 76% of nuclear bone marrow cells consisted of small cleaved lymphoblastic abnormal cells with or without barely visible nucleoli. Cytogenic study of cervical lymph node biopsy specimens showed a t(14;18)(q32;q21) chromosome translocation. Histologically the lymph node cells were classified according to the International Working Formulation as follicular small cleaved-cell lymphoma. Molecular analysis of DNA fragments of peripheral lymphocytes revealed both J-H gene and bcl-2 oncogene rearrangements. Immunophenotypes of peripheral lymphocytes, bone marrow cells and lymph node cells expressed a clonally distinct B-cell population bearing surface immunoglobulin-G, kappa-chain, CD-10, CD-19, CD-20, CD-21 and OKIa-1 antigens. We diagnosed this case as follicular lymphoma in the leukemic phase,

Adult↗
PubMed1992

Regional distribution of copper, zinc and iron in the brain in Long-Evans Cinnamon (LEC) rats with a new mutation causing hereditary hepatitis.

In Long-Evans Cinnamon (LEC) rats of three different ages (7, 13 and 32 weeks old) concentrations of Cu, Zn and Fe were measured in 8 regions of the brain. The LEC groups aged 7 and 13 weeks showed low concentrations of Cu in all regions compared to Long-Evans Agouti (LEA) rats. In 32-week-old LEC rats, however, Cu concentrations increased in 7 regions, in particular, significantly so in the striatum, hypothalamus, cerebellum, midbrain and cortex. Changes of Zn concentration were not found in any region. The Fe concentration increased in cortex and olfactory lobes. The three LEC groups showed a very high concentration of hepatic Cu and a low concentration of serum Cu compared to LEA rats. In LEC rats aged 32 weeks, however, hepatic Cu decreased and serum Cu increased compared to the other two LEC groups. These results suggest that the increase of the cerebral Cu concentration is closely related to the inherently abnormal Cu metabolism and then to the changes of Cu metabolism from about 13 weeks after birth.

Animals↗
PubMed1992

Circulating transferrin receptor in acute leukemias.

Serum transferrin receptor (s-TR) levels in acute leukemia patients were measured by a recently developed sandwich radioimmunoassay. The mean s-TR level for normal subjects (n = 205) was 246 +/- 79 (mean +/- 1 SD) ng/ml. The values for patients with untreated acute myelocytic leukemia (AML, n = 18) and untreated acute lymphocytic leukemia (ALL, n = 14) were 398 +/- 175 ng/ml and 479 +/- 176 ng/ml, respectively, both of which were significantly higher than those for the normal subjects (AML, p < 0.02; ALL, p < 0.05). When complete remission was achieved with initial remission induction therapy, s-TR decreased to 262 +/- 47 ng/ml (n = 22, 12 AML and 10 ALL), returning to normal levels. There was a good correlation between s-TR levels and the number of leukemic cells in peripheral blood (r = 0.743, n = 32, p < 0.01). In two patients with AML, serial changes of s-TR values and numbers of blast cells in the peripheral blood and bone marrow occurred in a parallel manner. If, therefore, this assay for s-TR can be made more sensitive, it may become useful for assessing acute leukemia activity and for monitoring the effects of therapy.

Acute Disease↗
PubMed1992

Effect of Krestin (PSK) on the induction of IL-2 activated killer cells.

The effects of Krestin (PSK) on the generation of lymphokine-activated killer (LAK) cells were examined in tumor-bearing mice. BALB/c mice were inoculated subcutaneously with methylcholanthrene-induced fibrosarcoma (Meth A) cells, and PSK was administered intraperitoneally every other day. The reduced LAK activity in tumor-bearing mice was restored by the administration of PSK. Since involvement of the humoral immunosuppressive factor in the impairment of LAK activity has been suggested, the effect of PSK on the impaired LAK activity in the presence of an immunosuppressive factor isolated from the ascites of X5563 (plasmacytoma)-inoculated mice was examined. The activity reduced by the immunosuppressive factor in an in vitro induction of LAK was restored by incubation with PSK. The antimetastatic effect of IL-2 was also augmented by its combined use with PSK. The data provide a rational basis for using PSK in combination with recombinant IL-2 in cancer immunotherapy.

Adjuvants, Immunologic↗
PubMed1991

A novel recombinant tumor necrosis factor-alpha mutant with increased anti-tumor activity and lower toxicity.

We prepared a novel recombinant tumor necrosis factor-alpha (TNF) mutant (mutant 471), in which 7 N-terminal amino-acids were deleted and Pro8Ser9Asp10 was replaced by ArgLysArg, and compared its biological activity with that of wild-type recombinant TNF. Mutant 471 had a 7-fold higher anti-tumor activity against murine L-M cells in vitro, and a higher binding activity to TNF receptors on L-M cells, than wild-type TNF. Furthermore, mutant 471 showed a higher anti-tumor effect on murine Meth A-HM tumors transplanted into BALB/c mice, with complete regression of the tumors being observed in the animals. The possible cachectin activity of mutant 471 was almost the same as that of wild-type TNF. The acute lethal toxicity of mutant 471 in beta-D-galactosamine-sensitized C3H/HeJ mice was 18 times lower than that of wild-type TNF. These results suggest that mutant 471 might be a more promising anti-cancer agent than wild-type TNF.

Amino Acid Sequence↗
PubMed1991

Human tumor-infiltrating lymphocytes transfected with tumor necrosis factor gene could augment cytotoxicity to autologous tumor cells.

Human tumor-infiltrating lymphocytes (TILs) derived from pleural or ascitic fluid were incubated with recombinant interleukin 2 and transfected with human tumor necrosis factor (TNF) alpha gene by the lipofection procedure. The resulting TILs secreted significant amounts of TNF in the culture supernatant and exhibited cytotoxicity against established cell lines, such as K562 and Daudi, and autologous tumor cells. The TNF gene-transfected TILs exhibited an augmented killing of autologous tumor cells.

Ascites↗
PubMed1991

Platelet aggregation induced by adenosine diphosphate released from cloned murine fibrosarcoma cells is positively correlated with the experimental metastatic potential of the cells.

We established five clones (ML-01, ML-02, MH-01, MH-02, MH-03) from murine 3-methylcholanthrene-induced fibrosarcoma A (Meth A), and investigated their experimental metastatic potentials in relation to their platelet-aggregating activities. A clone with a high metastatic potential (MH-02) showed a characteristic biphasic pattern of platelet aggregation, of which the first peak was not present in the aggregation patterns of the clone with low metastatic potential (ML-01). The first peak was eliminated by treatment of the cells with apyrase, indicating that adenosine diphosphate (ADP) was the causative substance of this particular peak. The metastatic potential of clones correlated well with the ADP concentration of the culture media. These results suggest that the increased ADP production and consequential enhancement of platelet-aggregating activity are closely related to the increment of pulmonary metastatic potential of MH-02 clone.

Animals↗
PubMed1991

Cytomegalovirus DNA in the sera of patients with cytomegalovirus pneumonia.

We attempted to detect cytomegalovirus DNA (CMV-DNA) in the sera of four leukaemia patients who underwent an allogeneic bone marrow transplant (BMT), in six leukaemia patients who suffered from pneumonia and in 16 healthy subjects, using the polymerase chain reaction (PCR). Three of the four BMT patients subsequently developed CMV pneumonia. In two cases, CMV-DNA was detected in the sera at about the time the pneumonia occurred, and the amount of DNA increased with disease progression. The serum of the third patient became positive for CMV-DNA before he developed pneumonia. The fourth patient did not develop CMV pneumonia, but his urine became persistently positive for CMV-DNA soon after the BMT, whereas the serum was negative. A relationship was found between the occurrence of pneumonia and the serum level of CMV-DNA. CMV-DNA was also detected in three of six pneumonia patients whose anti-CMV IgM antibodies were elevated in the circulation. Sera from the 16 normal subjects were negative for CMV-DNA, regardless of their being seropositive or seronegative for CMV. While it had been previously thought that CMV did not exist in serum, we detected CMV-DNA in serum by PCR in the active disease stage. Our results suggest that PCR would be useful for the early diagnosis of CMV pneumonia and in monitoring its course.

Adolescent↗
PubMed1991

Diagnostic value of measurement of serum type I procollagen carboxy terminal peptides in patients with scirrhous carcinoma of the stomach.

We have evaluated the radioimmunoassay for type I procollagen carboxy terminal peptide (type I C-peptide), which is liberated from type I procollagen during its conversion to collagen, in the serodiagnosis of scirrhous carcinoma of the stomach. The mean (SD) serum concentration of type I C-peptide in 39 normal subjects was 41.7 (19.7) ng/ml. The mean serum values and the positive ratio of type I C-peptide in 11 patients with stages II and III scirrhous carcinoma of the stomach were 91.2 (41.9) ng/ml and 54.5%, respectively. In 10 patients with other types of gastric carcinoma, the mean type I C-peptide values were not significantly different from the normal value. Serum type I C-peptide values reflected the clinical course of scirrhous gastric carcinoma in five patients who underwent either operation or chemotherapy. The measurement of serum type I C-peptide concentrations could provide a useful way of diagnosing and monitoring scirrhous carcinoma of the stomach.

Adenocarcinoma, Scirrhous↗
PubMed1991

Mechanism and clinical significance of soluble hepatic cell-surface receptors.

Transferrin receptors take up transferrin-iron complexes into hepatic cells. Although the receptor is not highly expressed in normal liver cells, malignant transformation of the cells increases its expression. As part of the expressed receptors are released into blood, a significant increase of serum receptors are observed in cases of hepatoma. Therefore, measurement of transferrin receptors in blood from patients with hepatoma may be useful for estimating the tumor burden and determinating therapeutic effects. Asialoglycoprotein receptors are expressed strongly in normal liver cells, whereas the expression is decreased in various chronic liver diseases and hepatoma. Although the active shedding of the receptors clearly occurs in vitro, as does that of the transferrin receptor, determination of the significance of these shed receptors in blood will require further studies.

Animals↗
PubMed1991

[Expression and extracellular release of transferrin receptors on erythropoiesis].

One of the most important factors for the proliferation and hemoglobin synthesis of erythroid cells is iron atom. This atom is tightly bound to serum transferrin (Tf) and is taken up by erythroblasts and reticulocytes through transferrin receptor (TfR). Both Tf and TfR are reutilizable and have roles for the efficient intracellular accumulation of iron. In addition to the reutilization (recycling), the expression of TfR is also regulated by cytoplasmic iron concentration; the increase of iron downregulate the synthesis of TfR at the translational level and vice versa. This mechanism was recently explained by the binding between "iron responsive element (IRE)" in the 5' end of TfR mRNA and IRE binding protein by a transacting manner. Johnstone et al, and we found that TfR was externalized from sheep reticulocyte and human erythroleukemia cell, K562, respectively. Furthermore, we confirmed that this shed TfR was detected in blood and concluded that the quantitation of TfR in serum is a useful index for evaluating the erythropoiesis. The serum TfR was increased in iron deficiency anemia, hemolytic anemia and polycythemia and was decreased in aplastic anemia. In renal anemia, it was increased after the administration of erythropoietin (Epo). By the in vitro liquid culture of peripheral blood stem cells using interleukin 3 and Epo, it was found that soluble TfR was derived from the erythroblasts during the maturation process.

Cell Differentiation↗
PubMed1991

[A remarkable effect of K-18 (IgG-melphalan complex) in a case of RAEB with hypoplastic marrow].

A 63-year-old male with refractory anemia with excess of blasts (RAEB) and hypoplastic marrow was treated with K-18 (240 mg/day P.O.). On admission, peripheral blood revealed pancytopenia. Bone marrow specimen revealed severe hypocellularity with 18.9% of the blast cells. Ten months later, the blast cells in the bone marrow decreased to 3.8%, and complete remission (CR) was obtained. CR was eight weeks. Duration of response (CR + PR) continued for about eight months. K-18 is an antitumor agent with minimal side effects, and seems to be effective for RAEB with hypoplastic marrow.

Anemia, Refractory, with Excess of Blasts↗
PubMed1990

The production of transforming growth factor-beta in acute megakaryoblastic leukemia and its possible implications in myelofibrosis.

Acute myelofibrosis is often associated with acute megakaryoblastic leukemia (AMKBL). Although the exact mechanism for the progression of myelofibrosis in AMKBL is unclear, certain humoral factors from megakaryoblastic cells, the precursors of platelets, may be involved in the enhancement of collagen synthesis by bone marrow fibroblasts. The present study, therefore, is an investigation of the possible pathogenic role of transforming growth factor-beta (TGF-beta), known to be a very potent collagen-stimulating factor found in platelets in the myelofibrosis of AMKBL. The results obtained were as follows: (1) Conditioned media from peripheral megakaryoblasts taken from an AMKBL patient and from established megakaryoblast cell lines (MEG-01) had much greater stimulatory effects on collagen synthesis in bone marrow fibroblasts than conditioned media from other leukemic cell types. (2) Based on an assessment of soft agar colony formation, there was greater TGF-beta activity in media that had been conditioned from megakaryoblasts than in media from other leukemic cell types. (3) When compared with other leukemic-cell types, megakaryoblasts showed substantially greater expression of TGF-beta mRNA that was hybridized at 2.5 kb with a TGF-beta cDNA probe, and TGF-beta polypeptides were detected at 13 Kd with anti-TGF-beta antibodies. (4) The addition of the anti-TGF-beta antibody inhibited the stimulatory effects of the megakaryoblast conditioned medium on collagen synthesis in bone marrow fibroblasts. These results clearly suggest that megakaryoblasts produce and secrete an active form of TGF-beta and stimulate collagen synthesis in bone marrow fibroblasts in a paracrine manner.

Animals↗
PubMed1990

Kinetics of internalization and cytotoxicity of transferrin-neocarzinostatin conjugate in human leukemia cell line, K562.

Human serum transferrin was conjugated with an anticancer-active polypeptide, neocarzinostatin, by using N-succinimidyl 1-3-(2-pyridyldithio)propionate. The conjugate consisted of 1.8 mol of neocarzinostatin per 1 mol of transferrin on average and retained cytotoxic activity against human tumor cells. This conjugate was capable of binding to the transferrin receptor of human myelogenous leukemia K562 cells and was internalized by endocytosis. The LD50 values of the conjugate and neocarzinostatin alone in the presence of excess native bovine transferrin were 0.20 microgram/ml and 1.80 micrograms/ml, respectively, suggesting that the effect of the conjugate was greater than that of neocarzinostatin alone. A pulse-chase experiment using 125I-labeled conjugate revealed that 25% of the internalized conjugate was degraded in lysosomes and the rest was recycled back to the cell surface without degradation. About 75% of this conjugate recycled back to the cell surface in 18.3 min (3.4 min for receptor binding and 14.9 min for recycling to the cell surface through the acidosomes), while the rest was delivered from the cell surface to the lysosome in 19.6 min. This phenomenon was confirmed by chasing the radioactivity in subcellular fractions separated by Percoll density gradient centrifugation. Therefore, it was concluded that this conjugate is internalized specifically by transferrin receptors and is at least partly transferred to and accumulated in lysosomal compartments, resulting in the inhibition of cellular DNA synthesis.

Antibiotics, Antineoplastic↗
PubMed1990

[Tumoricidal biological response modifiers (BRM)].

TNF, IFN, LT and IL-1 are well-known biological response modifiers (BRM) with cytocidal activity. Whereas carcinostatic agents generally derive their cytocidal action from their direct mutual reaction with target molecules (e.g., DNA, RNA), the cytocidal action of BRM resides in the enzyme response which ensures upon their binding to receptors. Accordingly, concomitant use of these drug of differing mechanism of action has a rationale. Considering that a certain kind of counteracting protein is present in cancer cells which are refractory or resistant to such cytokines, combination therapy with carcinostatic agents with inhibitive activity against such protein is also justified. In the same context the effects of TIL and LAK activated by IL-2 could be enhanced if the immune system should be modulated by combined use of BRM and carcinostatic agents such as CY. This paper discusses the results obtained with BRM and carcinostatic agents in combination in animal models and clinical cases.

Antineoplastic Agents↗