PubMed Health⌕ Search

Biomedical subjects

J Kuroda

Publications and source records attributed to J Kuroda.

At least 19 recordsLinked to original sources
PubMed2006

NK105, a paclitaxel-incorporating micellar nanoparticle, is a more potent radiosensitising agent compared to free paclitaxel.

NK105 is a micellar nanoparticle formulation designed to enhance the delivery of paclitaxel (PTX) to solid tumours. It has been reported to exert antitumour activity in vivo and to have reduced neurotoxicity as compared to that of free PTX. The purpose of this study was to investigate the radiosensitising effect of NK105 in comparison with that of PTX. Lewis lung carcinoma (LLC)-bearing mice were administered a single intravenous (i.v.) injection of PTX or NK105; 24 h after the drug administration, a proportion of the mice received radiation to the tumour site or lung fields. Then, the antitumour activity and lung toxicity were evaluated. In one subset of mice, the tumours were excised and specimens were prepared for analysis of the cell cycle distribution by flow cytometry. Combined NK105 treatment with radiation yielded significant superior antitumour activity as compared to combined PTX treatment with radiation (P=0.0277). On the other hand, a histopathological study of lung sections revealed no significant difference in histopathological changes between mice treated with PTX and radiation and those treated with NK105 and radiation. Flow-cytometric analysis showed that NK105-treated LLC tumour cells showed more severe arrest at the G2/M phase as compared to PTX-treated tumour cells. The superior radiosensitising activity of NK105 was thus considered to be attributable to the more severe cell cycle arrest at the G2/M phase induced by NK105 as compared to that induced by free PTX. The present study results suggest that further clinical trials are warranted to determine the efficacy and feasibility of combined NK105 therapy with radiation.

Animals↗
PubMed2005

Subversion of the Bcl-2 life/death switch in cancer development and therapy.

The Bcl-2 protein family, which largely determines commitment to apoptosis, has central roles in tumorigenesis and chemoresistance. Its three factions of interacting proteins include the BH3-only proteins (e.g., Bim, Puma, Bad, Noxa), which transduce diverse cytotoxic signals to the mammalian pro-survival proteins (Bcl-2, Bcl-x(L), Bcl-w, Mcl-1, A-1), whereas Bax and Bak, when freed from pro-survival constraint, provoke the mitochondrial permeabilization that triggers apoptosis. We have discovered unexpected specificity in their interactions. Only Bim and Puma, which mediate multiple cytotoxic signals, engage all the pro-survival proteins. Noxa and Bad instead bind subsets and cooperate in killing, indicating that apoptosis requires neutralization of different pro-survival subsets. Furthermore, Mcl-1 and Bcl-x(L), but not Bcl-2, directly sequester Bak in healthy cells, and Bak is freed only when BH3-only proteins neutralize both its guards. BH3-only proteins such as Bim are tumor suppressors and mediate many of the cytotoxic signals from anticancer agents. Hence, compounds mimicking them may prove valuable for therapy. Indeed, the recently described ABT-737 is a promising "BH3 mimetic" of Bad. We find that, like Bad, ABT-737 kills cells efficiently only if Mcl-1 is absent or down-regulated. Thus, manipulation of apoptosis by targeting the Bcl-2 family has exciting potential for cancer treatment.

Animals↗
PubMed2005

Serial changes in the regional cerebral blood flow of patients with hypertensive intracerebral hemorrhage -- long-term follow-up SPECT study.

We analyzed serial changes in the regional cerebral blood flow (rCBF) of 13 patients with intracerebral hemorrhage by single photon emission computed tomography (SPECT) during the acute- to chronic stage (2 hr to 55 weeks). The (99m)Tc-ethyl cysteinate dimmer ((99m)Tc-ECD) was used as the nuclear mediator. The SPECT timing within 48 hours after the onset was considered to be acute stage, from 48 hours to 4 weeks to be subacute stage, and after 4 weeks to be chronic stage. The region of interest was each hemisphere in the whole brain without ventricles at the thalamic level. For semi-quantitative analysis of rCBF, we used the Brain Uptake Ratio method. Of the 13 patients (mean age 65.5 years), 3 had thalamic-, 4 putaminal-, 5 subcortical-, and one a cerebellar hemorrhage; the hematoma volume varied from 4-50 ml (<20 ml, n=9; 20-30 ml, n=1; >30 ml, n=3; mean 17 ml). The rCBF changes during the long-term follow-up were classified as increase-, decrease-, and unchanged type. Of 5 patients with increased rCBF, 4 made a good recovery and one was severely disabled; of 5 patients with decreased rCBF, 1 made a good recovery, 3 were moderately-, and one was severely disabled. All 3 patients with unchanged rCBF were moderately disabled. Our findings suggest that among patients with hypertensive intracerebral hemorrhage, those with increased rCBF over time may have a favorable outcome. We further need more cases with intracerebral hemorrhage to clarify this trend.

Aged↗
PubMed2003

Increased expression of NAD(P)H oxidase subunits, NOX4 and p22phox, in the kidney of streptozotocin-induced diabetic rats and its reversibity by interventive insulin treatment.

AIM/HYPOTHESIS: An increased production of reactive oxygen species (ROS) could contribute to the development of diabetic nephropathy. NAD(P)H oxidase might be an important source of ROS production in kidney as reported in blood vessels. In this study, we show the increased expression of essential subunits of NAD(P)H oxidase, NOX4 and p22phox, in the kidney of diabetic rats. METHODS: The levels of mRNA of both NOX4 and p22phox were evaluated in kidney from streptozotocin-induced diabetic rats and age-matched control rats at 4 and 8 weeks after onset of diabetes by Northern blot analysis. The localization and expression levels of these components and 8-hydroxy-deoxyguanosine (8-OHdG), which is a marker of ROS-induced DNA damage, were also evaluated by immunostaining. RESULTS: The levels of both NOX4 and p22phox mRNA were increased in the kidney of diabetic rats as compared with control rats. Immunostaining analysis showed that the expression levels of NOX4 and p22phox were clearly increased in both distal tubular cells and glomeruli from diabetic rats. Both the localization and the expression levels of these components were in parallel with those of 8-OHdG. Interventive insulin treatment for 2 weeks completely restored the increased levels of these components in the diabetic kidney to control levels in parallel with those of 8-OHdG. CONCLUSIONS/INTERPRETATION: This study provides evidence that NAD(P)H oxidase subunits, NOX4 and p22phox, were increased in the kidney of diabetic rats. Thus, NAD(P)H-dependent overproduction of ROS could cause renal tissue damage in diabetes. This might contribute to the development of diabetic nephropathy.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed2003

Variable manifestation in natural killer cell leukaemia.

Natural killer (NK) cell leukaemias are a relatively rare group of haematological disorders, now entitled in the T/NK lymphoproliferative disorders in the new WHO classification. Recent studies have clarified their biological and clinical manifestation gradually. However, some cases with NK malignancies still remain difficult to diagnose and differentiate into their subtypes in the absence of a distinct diagnostic hallmark, especially at initial presentation. We describe herein five patients with NK leukaemias with respect to the clinical, cytological, immunological and cytogenetic characteristics, varied among each case. Cytologically, two aggressive NK cell leukaemia/lymphoma (ANKL/L) cases were a morphologically hypogranular variant form. Clinically, one with ANKL/L was presented as haemophagocytic syndrome without leukaemic infiltration. Systemic chemotherapy resulted in complete remission in one ANKL/L and two blastic NK cell leukaemia/lymphoma (BNKL/L) patients; however, a good long-term outcome was achieved in only one CD4-positive BNKL/L patient with allogenic bone marrow transplantation. Cytogenetic analysis revealed that recurrent chromosomal aberration was rare; however, two had aberrations at 10p11 and 11q13. From these findings, we conclude that comprehensive individual studies should be carried out in these patients to obtain a correct diagnosis and to design an optimal therapeutic approach.

Adult↗
PubMed2002

Non-myeloablative haematopoietic stem cell transplantation for severe aplastic anaemia with various complications.

We report a 20-year-old-male with severe aplastic anaemia who was treated with nonmyeloablative haematopoietic stem cell transplantation (NSCT) from a sibling donor. As the patient presented with complications consisting of mental retardation, severe obesity, a bone fracture, and recurrent infections, we selected NSCT instead of a myeloablative regimen, to reduce regimen-related toxicity (RRT). Conditioning therapy consisting of busulfan, fludarabine, antithymocyte globulin and FK506 was used to obtain immune suppression. RRT was limited and he is now in complete remission 19 months after NSCT. On day 91, he developed chronic graft-vs.-host disease; it was resolved by the combination of FK506, corticosteroids, and mycophenolate mofetil. Our experience contributes to the growing interest in NSCT as a modality for treating not only malignant haematological disorders associated with complications, but also nonmalignant haematological diseases.

Adult↗
PubMed2001

A novel superoxide-producing NAD(P)H oxidase in kidney.

During phagocytosis, gp91(phox), the catalytic subunit of the phagocyte NADPH oxidase, becomes activated to produce superoxide, a precursor of microbicidal oxidants. Currently increasing evidence suggests that nonphagocytic cells contain similar superoxide-producing oxidases, which are proposed to play crucial roles in various events such as cell proliferation and oxygen sensing for erythropoiesis. Here we describe the cloning of human cDNA that encodes a novel NAD(P)H oxidase, designated NOX4. The NOX4 protein of 578 amino acids exhibits 39% identity to gp91(phox) with special conservation in membrane-spanning regions and binding sites for heme, FAD, and NAD(P)H, indicative of its function as a superoxide-producing NAD(P)H oxidase. The membrane fraction of kidney-derived human embryonic kidney (HEK) 293 cells, expressing NOX4, exhibits NADH- and NADPH-dependent superoxide-producing activities, both of which are inhibited by diphenylene iodonium, an agent known to block oxygen sensing, and decreased in cells expressing antisense NOX4 mRNA. The human NOX4 gene, comprising 18 exons, is located on chromosome 11q14.2-q21, and its expression is almost exclusively restricted to adult and fetal kidneys. In human renal cortex, high amounts of the NOX4 protein are present in distal tubular cells, which reside near erythropoietin-producing cells. In addition, overexpression of NOX4 in cultured cells leads to increased superoxide production and decreased rate of growth. The present findings thus suggest that the novel NAD(P)H oxidase NOX4 may serve as an oxygen sensor and/or a regulator of cell growth in kidney.

Adult↗
PubMed2001

Collision-induced dissociation of ring-opened cyclic depsipeptides with a guanidino group by electrospray ionization/ion trap mass spectrometry.

The characteristics shown in the electrospray ionization/ion trap mass spectra of ring-opened LI-F antibiotics (cyclic depsihexapeptides with a 15-guanidino-3-hydroxypentadecanoic group as a side-chain) were examined. Collision-induced dissociation (CID) MS of protonated molecules of the depsipeptides produced many fragment ions. Most of these fragment ions contained information for determining the amino acid sequences of antifungal antibiotics. The fragment ions were classified into six groups (b(n'), B(n'), B'(n'), beta(n'), y(n) and Y(n)). According to MS(3) spectra, the B(n'), B'(n) and beta(n) ions can be considered to be derived with a cleavage at each CO--NH in the peptide bonds of [MH--NH(3)](+),[MH--NH(3)--OH](+) and [MH--NH(3)--2H(2)O](+), respectively, in ion trap MS. Losses of NH(3) and H(2)O from the amino acid residues of the depsipeptides in ion trap MS are likely to be smaller than those from the side-chain. The measurements with electrospray ionization (ESI)/ion trap MS of depsipeptides with a side chain containing polar groups may provide useful information for structural determination.

Anti-Bacterial Agents↗
PubMed2001

Agranular CD4+CD56+ blastic natural killer leukemia/lymphoma.

Blastic natural killer cell leukemia/lymphoma (blastic NKL/L) is characterized by blastic morphology and a distinctive immunophenotype combining blastic features and cytologically resembling acute myeloid or lymphoid leukemia. The clinical, pathologic, and cytogenetic features of blastic NKL/L have not yet been systematically identified. We report herein a case of blastic NKL/L with skin lesion, adenopathy, and systemic lymphoadenopathy. The identified tumor cells were positive for CD4 and CD56, and negative for T-cell, B-cell, and myeloid markers. T-cell receptor beta, gamma, delta, and immunoglobulin heavy chain genes in the bone marrow cells showed germ-line configurations. Southern blot analysis with a terminal probe did not reveal any Epstein-Barr virus infection. Although patients diagnosed as blastic NKL/L have generally shown chemotherapy resistance and poor prognosis, our patient was treated with a combined chemotherapy, which is also used for acute lymphoblastic leukemia, and has maintained complete remission (CR) for more than 13 months. In addition to clinical investigations, we thoroughly analyzed his karyotype by using a combination of G-banding and a new technique, spectral karyotyping. The karyotype was described as 45, XY, der(1)t(1;20)(p32;q11.2), der(6) (1pter-->1p32:: 6p21.1-->6q13:: 7q11.2-->7qter), der(7) t(7;20)(q11.2;q11.2), t(13;14)(q14;q32), der(13)t(6;13) (p21.1; q14), -20.

Adult↗
PubMed2001

Primary hepatic Burkitt's lymphoma with chronic hepatitis C.

The liver is an uncommon primary site for malignant lymphoma, and primary hepatic lymphoma has been found to make up 0.4% of all extranodal lymphomas. We report a rare case of a 75-year-old Japanese male with primary hepatic Burkitt's lymphoma, according to both the revised European-American Lymphoma classification and the new World Health Organization classification. As not only histological findings but also immunological features are deemed essential in the diagnosis of Burkitt's lymphoma, the previous 7 cases of primary hepatic Burkitt's lymphoma were not fully evaluated, using these criteria. As far as we know, this is the first case of primary hepatic Burkitt's lymphoma with typical features on histological, immunological and cytogenetical analysis. He had a history of chronic hepatitis C over several decades with subsequent liver cirrhosis. From our review of the literature and our case, the relationship between hepatitis C virus infection and the development of primary hepatic Burkitt's lymphoma remains obscure.

Aged↗
PubMed2001

Treatment of steroid-resistant idiopathic thrombocytopenic purpura in pregnancy with repeated high-dose intravenous immunoglobulin.

High-dose intravenous immunoglobulin (HD-IVIG) has temporary but reliable efficacy in idiopathic thrombocytopenic purpura (ITP). HD-IVIG has been described as the representative management in pregnant cases of refractory to corticosteroid or immunosuppressants. There have been few cases treated with repeated HD-IVIG to sustain pregnancy from the early phase of pregnancy. This case report describes a pregnant case of steroid-refractory ITP, treated with six times repeated HD-IVIG, resulting in the successful delivery of a healthy newborn with a normal platelet count. No adverse effects were observed.

Adolescent↗
PubMed2001

Trisomy 8 involved in myelodysplastic syndromes as a risk factor for intestinal ulcers and thrombosis--Behçet's syndrome.

Only 12 myelodysplastic syndrome (MDS) cases with Behçet's syndrome have been previously reported and trisomy 8 was found to have accumulated in all these patients. Five of the cases had complications in the form of multiple intestinal ulcers, which is one of the symptoms of Behçet's syndrome. To investigate the relationship between trisomy 8 and multiple intestinal ulcers in MDS patients, we analyzed 46 MDS cases treated in our hospital over the last decade, and trisomy 8 was observed in eight of them. Three of these cases had complications of both multiple intestinal ulcers and thrombosis, and two cases showed episodes of thrombosis without intestinal ulcers. All these five cases featured trisomy 8, while the other 38 MDS patients without trisomy 8 had no episode of either intestinal ulcer or thrombosis. Two of the three cases suffering from multiple intestinal ulcers were treated with granulocyte-colony stimulating factor (G-CSF), which resulted in aggravation of the symptoms. Although the influence of G-CSF on such symptoms in MDS patients with trisomy 8 remains unclear, it seems advisable to exercise caution in the use of G-CSF when an MDS patient with trisomy 8 has intestinal ulcers or thrombosis.

Adult↗
PubMed2000

Localization of initial lymph node metastasis from carcinoma of the thoracic esophagus.

BACKGROUND: Most surgeons consider esophageal carcinoma with lymph node involvement a systemic disease. However, it is possible that the disease may be localized in the earlier phases of lymphatic metastasis. The distribution of involved lesions in the initial phase of lymph node metastasis has not been thoroughly investigated yet. METHODS: Among 329 patients that underwent curative (R0 International Union Against Cancer [UICC]) esophagectomy with systematic mesoesophageal dissection, 51 cases of patients with only 1 involved lymph node (solitary involvement) were retrospectively investigated and compared with patients with multiple involved lymph nodes. The regional lymph nodes were divided into the thoracocervical junction group (lower deep cervical and recurrent nerve lymph nodes), perigastric group, and intrathoracic group. RESULTS: Lymph node involvement was limited to a solitary lymph node in 46% of lymph node positive patients with esophageal carcinoma confined to the wall (T1 and T2, UICC) and in 17% of lymph node positive patients with cancer that invaded the extramural layer (T3 and T4, UICC). Of patients with solitary involvement, 82% had a positive thoracocervical junction or perigastric lymph node. The 5-year survival rate in solitary involvement cases was 61%, and 65% when solitary involvement was not intrathoracic. Most of the 5-year survivors had involvement of a thoracocervical junction or perigastric lymph node and had not received systemic chemotherapy. CONCLUSIONS: Solitary involvement was not rare and not directly associated with a disseminated disease. Solitary involvement was commonly located in the thoracocervical junction or abdomen that are accessible without thoracotomy. Systematic dissection of the regional lymph nodes including thoracocervical junction and perigastric groups is recommended for resectable esophageal carcinoma at this time. However, less extensive dissection may be performed in selected cases if the sentinel lymph node concept proves valid.

Esophageal Neoplasms↗
PubMed2000

c-myc overexpression is not mandatory in aggressive-phase multiple myeloma with Burkitt's type translocation.

This report concerns a case of aggressive-phase multiple myeloma (AGMM) with Burkitt's type translocation t(8;14)(q24;q32), detected by Giemsa-banding. Double-color fluorescence in situ hybridization identified the breakpoint on 8q24 at a comparatively centromeric site, which was at least 300 kb and possibly 600 kb distant from the c-myc coding region. The breakpoint on 8q24 of the present case was far removed from that seen in other B-cell neoplasms with t(8;14)(q24;q32). Despite the presence of t(8;14)(q24;q32), neither rearrangement nor overexpression of the c-myc gene was observed in this case. Although our case may be a special case of multiple myeloma, it nevertheless suggests that overexpression of c-myc is not mandatory in an AGMM patient with Burkitt's type translocation. t(8;14)(q24;q32) which was seen in our case represents one of the first to be mapped at more than 300 kb 5' of c-myc. It should also be noted that this result could mean that a centromeric boundary 5' of c-myc exists where the influence of the immunoglobulin (Ig) H enhancer on c-myc transcription is not effective.

Aged↗
PubMed2000

Aggressive natural killer cell leukemia/lymphoma: a comprehensive cytogenetic study by spectral karyotyping.

A 38-year-old male presented with fever and hepatosplenomegaly. Cells that had infiltrated to the bone marrow were consistent immunophenotypically and genotypically with natural killer (NK) cells. Oligoclonal Epstein-Barr virus infection was detected in the bone marrow cells. The patient was diagnosed as a case of aggressive NK cell leukemia/lymphoma. Combined chemotherapy was not effective and death occurred shortly after presentation. Although the karyotype of this case was too complicated to be accurately identified only by G-banding, spectral karyotyping (SKY) analysis not only identified all chromosomal materials of unknown origin, but also detected the cryptic translocation on the apparently normal chromosome. Moreover, SKY analysis identified der(4)t(4;14)(q12;q11.2). The chromosomal band 14q11.2 is a recurring breakpoint in T-cell non-Hodgkin's lymphoma, and is also the locus of the delta chain of the T-cell receptor. To our knowledge, t(4;14)(q12;q11.2) in T-cell or NK-cell malignancies has not been previously reported.

Adult↗
PubMed2000

Accurate mass measurement of low molecular weight compounds by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.

We report the application of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) for the accurate measurement of mass of low molecular weight compounds (smaller than 1500 Da), a linear peptide, two types of cyclic depsipeptides, a polyhydroxy-macrocyclic lactone, and two prenylated flavonoids, with delayed extraction in the reflector mode. The performance of the MALDI-TOF instrument was less than those of fast atom bombardment and Fourier-transform ion cyclotron resonance mass spectrometry instruments and insufficient to give acceptable accuracy for literature reporting. Nevertheless, when combined with NMR spectrometry and/or amino acid analysis to give information on the numbers of carbon atoms and index of hydrogen deficiency, MALDI was useful for determination of the elemental composition of the low molecular weight compounds available in small quantities.

Angiotensin II↗