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Biomedical subjects

M Kikuchi

Publications and source records attributed to M Kikuchi.

At least 703 records · Page 39Linked to original sources

Myxoid liposarcoma with t (12; 16)(q 13; p 11). Possible usefulness of chromosome analysis in a poorly differentiated sarcoma.

A chromosomal study was used to establish diagnosis of a poorly differentiated soft-tissue sarcoma occurring in the right thigh of a 57-year-old Japanese female. Histopathologically the excised tumor consisted of a poorly differentiated myxoid neoplasm, without specific features to enable the identification of neoplastic cells. Although a tentative diagnosis of poorly differentiated myxoid liposarcoma was made, ultrastructural examination and Oil Red O fat stain failed to demonstrate the evidence of lipoblastic differentiation, except that occasional cells possessed a small number of fine fat droplets. The diagnosis of liposarcoma was suggested by chromosome analysis of the fresh tumor tissue after short time culture and trypsin-Giemsa banding technique. The tumor cells demonstrated a clonal abnormality characterized by a reciprocal translocation, t(12; 16)(q 13; p 11), which is known as a specific aberration in myxoid liposarcoma. Thus, chromosome study seems to be useful for identifying undifferentiated mesenchymal tumors, which lack morphologic evidence of any specific differentiation, as in the present case.

Cell Differentiation↗

Antigen responsive antibody-receptor kinase chimera.

We have constructed chimeric receptors, combining murine IgM and the cytoplasmic portion of human epidermal growth factor receptor (EGFR), with the aim of developing a novel immunosensor with antigen-dependent phosphorylation activity. When intact IgM was used, the chimeric receptor showed both antigen binding and protein tyrosine kinase activity, but the kinase activity was constitutive and independent of antigen binding. However, with IgM lacking the CH2 domain, the autophosphorylation activity increased with increasing concentrations of anti-IgM or hapten-BSA conjugate. Monovalent hapten could not induce phosphorylation but inhibited stimulation by hapten-conjugated BSA.

Animals↗

Induction of ovarian growth and ovulation by administration of a chicken gonadotrophin preparation to Japanese quail kept under a short-day regimen.

1. Chronic administration of a glycoprotein fraction from chicken pituitary using an ALZET osmotic pump at 12.5 micrograms/h for 2 weeks induced growth of ovarian follicles to a mature size in the ovary and deposition of yolk in sexually immature 6-week-old Japanese quail females which were kept under 8L:16D short-day conditions. However, no ovulation was induced in these birds. 2. Injection of 500 micrograms of the glycoprotein into other immature short-day females was performed following the above chronic administration, 12 or 14 and 15 d after implantation of the osmotic pump. About 24 h after injection, 3 of 14 females laid one or two eggs. Ovulation was confirmed in 4 females by autopsy. A total of 5 of 14 females ovulated 6 eggs, and significant development of the oviduct and the cloacal opening were observed in all of the treated females. 3. Thus, complete ovarian function could be induced in sexually immature female Japanese quail by administration of avian gonadotrophin using a combination of an osmotic pump and an injection.

Animals↗

Malignant fibrous histiocytoma. Proliferative compartment and heterogeneity of "histiocytic" cells.

To elucidate the precise origin and characteristics of the proliferating cells in malignant fibrous histiocytoma (MFH), the authors analyzed 33 MFH tumors, using immunohistochemical techniques with a panel of 12 antibodies. All three types of MFH cells (spindle cells, polygonal cells, and bizarre giant cells) stained positively for mesenchymal antigens (FU3 and vimentin) but did not stain for macrophage/histiocyte markers (HAM 56 and CD68). Therefore, the MFH cells may not represent true histiocytes, although they may be mesenchymal-derived cells behaving as "facultative histiocytes" with superficial resemblance to actual histiocytes. Normal histiocytes in the stroma tested positive for macrophage/histiocyte antigens; the most common cells were HAM 56-positive cells constituting 30-80% of nonneoplastic stromal cells, followed by those positive for CD68 (10-50%), Mac 387 (less than 2%), and S-100 protein (less than 1%). Our results indicate the presence of heterogeneity of "histiocytic" cells in MFH. Proliferating-cell nuclear antigen (PCNA) was expressed not only in the spindle and polygonal MFH cells but also in the bizarre giant cells. These findings suggest that all three types of MFH cells participate in the proliferative compartment of MFH. Uneven PCNA staining of the irregular nuclear segments of the bizarre giant cells may result in abnormal DNA synthesis, possibly contributing to the marked diversity of nuclear morphology in MFH. Touton-type and osteoclast-like giant cells did not stain for PCNA but stained positively for histiocytic markers. Therefore, these giant cells may lack proliferative activity and probably result from normal histiocytes fusing together.

Adult↗

In vitro anti-tumor activity of anti-c-erbB-2 x anti-CD3 epsilon bifunctional monoclonal antibody.

With the aim of developing an effective cancer immunotherapy for common epithelial cancer, a new class of bifunctional antibody (BFA) was developed; one arm of this BFA recognized c-erbB-2 gene product, and the other arm recognized CD3 epsilon, a T-cell specific surface antigen. Application of this BFA with human peripheral blood lymphocytes exhibited specific anti-tumor activity in vitro on a breast tumor cell line, ZR-75-1, which expressed abundant c-erbB-2 gene product on its cell surface. These results indicate that BFA recognizing an oncogene product on cell surface is a potential new agent for cancer immunotherapy.

Antibodies, Monoclonal↗

Human lung cancer cell line producing hepatocyte growth factor/scatter factor.

Hepatocyte growth factor (HGF)/scatter factor (SF) is a cytokine which is produced by mesenchymal cells and stimulates the motility of some epithelial cells, including cancer cells and vascular endothelial cells. Two human lung cancer cell lines, PC-1 and PC-13, were found to produce a protein which was indistinguishable from HGF/SF with regard to biological activities and immunological characteristics, although they were derived from epithelial cells. In general, highly aggressive cancer cells often show some mesenchymal characteristics, and production of HGF/SF by cancer cells is also considered as a phenomenon of acquisition of mesenchymal phenotype, which may be involved in cancer invasion and progression. These cell lines showed no apparent response to exogenous HGF/SF. In addition, no c-met proto-oncogene product was detectable in these cells by Western blot analysis. Although the function of HGF/SF produced by cancer cells, either autocrine or paracrine stimulation, remains to be studied, this is the first report to describe cancer cells producing HGF/SF.

Blotting, Western↗

Interstitial 9q deletion in T-lymphoid/myeloid biphenotypic leukaemia.

We report the biological characteristics of leukaemic blasts from two cases of acute leukaemia with an interstitial deletion of the long arm of chromosome 9 (9q-). Case 1 (FAB: M1) showed del(9)(q12q22) as the sole karyotypic anomaly, and case 2 (FAB: M1) presented del(9) (q12q22) in association with trisomy 10. In both cases, leukaemic blasts presented unique cytological features, such as prominent vacuoles on Giemsa staining, or strong localization of myeloperoxidase resembling 'pseudo-Chediak-Higashi' granules. Immunophenotyping of blasts revealed the biphenotypic expression of T-lymphoid/myeloid antigens (CD2, CD7/CD33) in addition to CD34. Neither T-cell receptor beta (TCRB), T-cell receptor gamma (TCRG) nor Ig heavy chain (IGH) genes were clonally rearranged. Furthermore, there was neither rearrangement nor expression of ABL, which is located at 9q34, indicating that the deletion involved bands centrometric to 9q34 did not induce the activation of ABL. DNA synthesis of the blasts was stimulated (stimulation index greater than 2.0) in the presence of interleukin (IL)-3, IL-4, granulocyte colony-stimulating factor or erythropoietin (Epo). IL-3 and IL-4 could also support the in vitro growth of leukaemic blast colonies, and the IL-3- or IL-4-dependent blast colony growth was synergistically enhanced by the addition of IL-6 or Epo. These observations imply that T-lymphoid/myeloid or pluripotent stem cells may be closely involved in the development of 9q- AML.

Adolescent↗

Fine needle aspiration cytology of high grade T-cell lymphomas in human T-lymphotropic virus type 1 carriers.

We studied the fine needle aspiration (FNA) cytology of high grade peripheral T-cell lymphomas from eight human T-lymphotropic virus-1 (HTLV-1) positive patients. FNA smears from seven lymphomas showed a distinctive cytologic pattern with a dominance of rounded cells with irregular nuclei and a moderately basophilic cytoplasm. Irregular cells with a pale abundant cytoplasm were present in varying amounts. Some smears contained a few giant cells with cerebriform nuclei. In addition, plasma cells and eosinophils were found. Epithelioid cells were an inconstant finding. On histology these seven lymphomas were assigned to the pleomorphic medium-large cell subtype and all but one were of T-helper phenotype with rearrangements of the T-cell receptor. FNA smears from a lymph node in a patient with a previous histological diagnosis of lymphomatoid papulosis of the gingiva showed a monotonous pattern of large immunoblastic cells with some binucleated variants consistent with a diagnosis of high grade immunoblastic lymphoma, which was confirmed histologically. Our results show that peripheral T-cell lymphomas from HTLV-1 positive patients have cytological patterns which are distinctive enough to allow a conclusive diagnosis of high grade T-cell lymphoma. However, we do not think that the cytology of HTLV-1 positive lymphomas can be differentiated from that of virus-unrelated high grade T-cell lymphomas.

Adult↗

[Isolation of verocytotoxin-producing Escherichia coli from cattle and pets].

During a three-year period (1987 & 1990), a comprehensive attempt was made to isolate verocytotoxin-producing Escherichia coli (VTEC) from 96 bovine, 89 porcine, 67 canine and 18 feline cases suffering from gastroenteritis. VTEC were isolated from 11 cows and 1 cat. Bead-ELISA and oligonucteotide probes were used to type the verotoxins (VT) and it was found that the VTEC strains from cows produced not only the currently recognized VT1, VT2 and VT2vh but also produced two new VT's tentatively designated as VTx and VTy. The strain from the cat produced VTy. Serotyping of the strains revealed that some animal strains belonged to similar serotypes as those isolated from human patients with hemorrhagic colitis and hemolytic uremic syndrome. Cattle, especially cows, and domestic pets apparently are reservoirs of VTEC and probable sources of infection in our country as has been previously documented in Canada and USA.

Animals↗

Suction effusion fluid from skin and constituent analysis: new candidate for interstitial fluid.

The authors analyzed the constituents of effuse transcutaneous fluid, labeled suction effusion fluid (SEF), and monitored its glucose concentration during glucose loading in rabbits (Japan White, female) under pentobarbital anesthesia. The SEF was sampled by suctioning corneal layer-stripped skin at 400 mmHg absolute pressure. The SEF proved to have nearly the same concentrations as serum for lower-molecular-weight substances such as glucose, creatinine, and urea nitrogens, but not for higher-molecular-weight substances such as serum proteins. The SEF protein concentration was one-fourth that of serum protein. Proteins > 100 kDa molecular mass were barely detectable in the SEF. Monitoring of SEF glucose change every 10 min during intravenous glucose loading was successfully accomplished, and SEF glucose concentration followed blood glucose concentration with a 10-min delay. The SEF was thought to consist of interstitial fluid and/or effuse fluid from small vessels in subcutaneous tissue.

Animals↗

Modulation of progesterone secretion by androgens in porcine granulosa cell cultures.

The influence of testosterone, androstenedione and dihydrotestosterone (DHT) on the progesterone (P4) production by cultured porcine granulosa cells was studied in the presence or absence of gonadotropins. Porcine granulosa cells from large follicles (6-12 mm in diameter) were incubated for 2 days with 5% CO2 in air with testosterone, androstenedione and DHT (10(-12), 10(-10), 10(-8) and 10(-6) M) in the presence or absence of luteinizing hormone (LH, 10 ng/ml) or follicle-stimulating hormone (FSH, 30 ng/ml). P4 and pregnenolone (P5) in conditioned culture media were quantified by their specific RIAs. In the absence of gonadotropins, P4 in media with androgens were not significantly different from controls. In the presence of LH, the addition of testosterone (10(-10), 10(-8) M), androstenedione (10(-8) M) and DHT (10(-8) M) caused a significant 1.3- to 2.3-fold increase in P4 over that caused by LH alone. In contrast, in the presence of FSH, testosterone (10(-12), 10(-10) M), androstenedione (10(-12)-10(-6) M) and DHT (10(-6) M) reduced the levels of P4 by 22% to 41%. The addition of androgens with LH caused a significant increase in P5, while P5 decreased in the presence of FSH. P4/P5 ratios remained unchanged in the presence of both LH and FSH. These data suggest that the P4 production by cultured porcine granulosa cells is modulated in a paracrine or an autocrine fashion by androgens in the presence of gonadotropins, and that androgens may exert their actions partly by altering the activity of cholesterol side chain cleavage enzymes.

Androgens↗

A serial observation of coronary thrombi in vivo by a new percutaneous transluminal coronary angioscope.

This study was undertaken to observe coronary thrombus formation serially from an antegrade perspective by means of a new thin flexible angioscope that has an inflatable balloon at the distal tip and an angulation mechanism. To test its capabilities, thrombi were induced in the left anterior descending coronary artery of 11 dogs by copper coils, and the thrombi were then observed through this angioscope, which had been introduced into the coronary artery by a guide catheter. Five minutes after insertion of the copper coil, fibrin-like material and white components of the thrombi were seen massing around the copper coil. Then, thin, mixed thrombotic white and red components formed around the copper coil. At fifteen minutes after the copper coil insertion, the thrombi grew in size. Ten minutes later, the thrombi finally obstructed the coronary lumen in most dogs. The red and white appearance of these thrombi was confirmed macroscopically, and the microscopic findings of these occluding thrombi revealed a fibrinous network with platelet aggregates and blood cell coagulation. Though ordinary angiography cannot reveal the precise features of the various coronary thrombi, this new angioscope was able to discern them from the antegrade perspective. The capabilities of this angioscope, which enabled these findings, should prove helpful in evaluating the stages of human coronary thrombosis. Of additional benefit, this angioscope can be used clinically for cardiac catheterization.

Animals↗

[Immunohistochemical in situ demonstration of cytokines in Hodgkin and non-Hodgkin lymphoma].

Primary biopsies from 149 patients with malignant lymphomas were examined by histological and immunohistochemical techniques. Twenty eight cases were classified as Hodgkin's disease and 121 as non-Hodgkin's lymphomas. The immunohistochemical distribution of cytokine expression (Il-1 alpha, Il-1 beta, Il-6 and TNF-alpha) was demonstrated in neoplastic cells and in tumor-associated macrophages (TAM). Neoplastic cells showed mostly weak positivity for TNF-alpha in 40% of Hodgkin's disease and in 20% of T cell lymphoma cases. Two groups of malignant lymphomas were established which differed in the numbers of cytokine expressing TAM. The first group consisted of malignant lymphomas which contained large quantities of cytokine-possessing TAM. In the second group significantly lower frequencies of cytokine expressing TAM were found. In both groups high and low grade malignant lymphomas were encountered. There was a significantly positive correlation between the number of Il-6 possessing TAM and the proliferation of lymphoma cells in only the non-Hodgkin's lymphomas. Our results suggest a paracrine tumor growth stimulating mechanism which is created by a self perpetuating cytokine production loop. A supposed cytokine produced by neoplastic cells dependent from their proliferative activity may induce Il-6 secretion by TAM. Il-6 in turn may stimulate the proliferation of the lymphoma cells without maturation thus leading to a self-sustaining growth.

Antibodies↗

[Clinical analysis of 10 patients with chronic lymphoid leukemia].

Ten patients with chronic lymphoid leukemia were analyzed for clinical characteristics, morphology and phenotype of leukemic cells. There were 3 patients with T-chronic lymphocytic leukemia (CLL), 2 with T-prolymphocytic leukemia (PLL), 2 with B-CLL, 1 with B-PLL, 1 with non-T-non-B-CLL and 1 with Waldenström's macroglobulinemia. Although chronic lymphoid leukemia is usually characterized by proliferation of B-lymphocytes, our study revealed that 5 of 10 patients had T-cell phenotype. A peripheral blood specimen of T-CLL showed small lymphocytes with a mature appearance and an irregular nuclear margin. Most of the cells lacked large azurophilic granules in the cytoplasm and nucleoli were also inconspicuous in the nucleus by light and electron microscopic examinations. In PLL, a majority of the cells were large lymphocytes with a prominent nucleolus and abundant basophilic cytoplasm which were more clearly observed by transmitted electron microscopic examination. The patients were treated with cyclophosphamide and prednisolone, but response to treatment was transient. The median survival time was 7 months for all patients, while that of T-cell lineage cases was only 1 month. Therefore, new modalities of treatment must be investigated in the future.

Aged↗

[Pathological examination of 11 autopsy cases of acute onset interstitial pneumonia of unknown etiology].

In 11 autopsy cases of acute onset interstitial pneumonia of unknown etiology, all cases had thickening of alveolar septa with various degrees of lymphocytic infiltration and fibroblast proliferation. Only a few cases had edematous alveolar septa, which were weakly positive in alcian-blue staining. Intra-alveolar, intra-alveolar duct and intra-bronchiolar organization was a characteristic finding. These findings may represent the repair phase rather than the exudative phase of diffuse alveolar damage. Localized bacterial pneumonia was superimposed in 3 cases, and neither Pneumocystis carinii nor viral inclusion bodies were identified in any case. The severity of fibrosis was not obviously correlated with the period of artificial ventilation. From these findings, terminal infection and oxygen therapy did not seem to significantly modify the course of acute-onset interstitial pneumonia. Further examination of autopsy cases as well as open-lung biopsy is important to elucidate the time course of acute-onset interstitial pneumonia.

Acute Disease↗

[Clinical evaluation of sulbactam/cefoperazone for severe infections associated with hematological disorders].

The combination therapy of sulbactam/cefoperazone (SBT/CPZ) and piperacillin (PIPC) was evaluated in 49 patients with severe infections associated with hematological disorders. Clinical responses in 43 evaluable patients out of the 49 patients were excellent in 12, good in 18, thus, overall efficacy rate was 69.8% (excellent plus good). Efficacy rates of this combination therapy were 60% (3/5) for sepsis, 75% (21/28) for suspected sepsis, and 50% (4/8) for pneumonia. The efficacy rate was 71.4% (10/14) in patients with neutrophil counts less than 200/microliters; this combination therapy was highly effective even in the neutropenic patients. Transient increases in hepatic function test values were observed in 2 patients, but no other side effects were observed during the combination therapy. From these observations it appears that the combination therapy of SBT/CPZ and PIPC is a very useful empiric therapy for severe infections associated with hematological diseases.

Adolescent↗

[A case of rheumatoid arthritis complicated with pseudotumor around odontoid process successfully treated by methotrexate].

A 69-year-old-female with a history of rheumatoid arthritis since 1975 had suffered from dysesthesia of extremities since October 1989. Radiating pain and weakness occurred when she tried to stand up on Dec. 25 in 1989. She was admitted to our hospital in October 1990. Physical examination showed emaciation, hypesthesia of extremities, hypesthesia over the right chest and back, impaired vibration and position sense, and hyperreflexia. Laboratory findings revealed that the erythrocyte sedimentation rate was elevated to 46mm/hr, rheumatoid factor (RF) to 83.1IU/ml and CRP to 3.7mg/dl. Her blood sugar was high and she was diagnosed as having diabetes mellitus. Cervical X ray film showed atlanto-axial subluxation. A pseudotumor around the odontoid process bulging into the spinal canal and compression of the upper cervical cord was observed by MRI. In spite of administration of bucillamine (100mg/day), the size of pseudotumor did not change. Methotrexate (MTX) at a dose of 5mg/week was started in February 1991 and the pseudotumor decreased in size with a concurrent reduction of ESR, RF and CRP. However, the high intensity lesion by T2 weighed image did not change and dysesthesia persisted. The pseudotumor was thought to be due to pannus and it was revealed that MTX was effective for reduction. The persistent dysesthesia was probably due to the degeneration of the upper cervical cord, although diabetic neuropathy may also have played a role.

Aged↗

[Increased serum levels of human cardiac myosin light chain 1 in patients with renal failure].

In this study, we measured cMLC1 concentration in serum and urine from patients with acute myocardial infarction (AMI), chronic renal failure (CRF), and various grades of renal dysfunction (RD) in comparison with normal controls, by using enzyme immunoassay (EIA) with monoclonal antibody, and attempted to elucidate the mechanism of increased serum level of cMLC1 in patients with renal failure. The serum level of cMLC1 of CRF patients under maintenance hemodialysis (HD) was 20.3 +/- 19.6 ng/ml, markedly higher than normal controls (0.54 +/- 0.55 ng/ml). The patients with RD and CRF under conservative therapy had higher serum cMLC1 level than normal controls especially in advanced CRF, while each value not correlating with their creatine clearance (Ccr). cMLC1 in urine was detectable in only two cases with AMI accompanied with CRF or RD. In addition, immunohistological studies of renal biopsy specimens from RD patients did not show cMLC1 deposits in glomerulus. These results suggest that cMLC1 is assumably filtered through the glomerulus, and then absorbed in the renal tubule.

Humans↗