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Biomedical subjects

R Suzuki

Publications and source records attributed to R Suzuki.

At least 199 records · Page 11Linked to original sources

[Irinotecan (topoisomerase-I inhibitor) for the treatment of recurrent primary intracranial malignant lymphoma].

Primary intracranial malignant lymphoma is a fetal disease with poor prognosis, and there is no effective treatment against recurrent primary intracranial malignant lymphomas. We report 3 cases of malignant lymphoma treated with irinotecan (topoisomerase-I inhibitor, camptothecin derivatives), an aromatic drug extracted from camptotheca acuminata. After the initial diagnosis, surgical resection followed by radiation therapy was performed for one cerebral, and two cerebellar malignant lymphomas. The tumors recurred 1 month, 18 months, and 18 months after the initial treatment, respectively. The former two cases were treated with additional radiation therapy and/or radiosurgery for the recurrent tumors; however, the tumors recurred again. All cases were treated finally with a combination therapy of irinotecan and cis-platinum followed by a maintenance therapy with irinotecan only. All cases showed a sharp roentgenographical response to the chemotherapy even after cumulative recurrences. One patient died of systemic infection, and another died of intracranial tumor recurrence 11 and 29 months after the initial diagnosis, respectively. Autopsies revealed multiple tumor recurrences in both these cases. The other patient died 31 months after the initial diagnosis, also due to intracranial tumor recurrences. These results indicate the usefulness of irinotecan for the treatment of recurrent primary intracranial malignant lymphoma; however, further investigation is necessary to establish a better protocol for irinotecan treatment against primary intracranial malignant lymphoma.

Aged↗

[Ki-1 lymphoma].

ALCL is widely recognized with its broad morphologic and phenotypic spectrum causing controversy in the diagnosis of this peculiar neoplasm. It is now beyond doubt that a significant proportion(64 to 84%) of the cases diagnosed as ALCL is closely associated with the expression of chimeric NPM-ALK protein activated by the (2;5) (p23;q35) chromosomal translocation, which can be detected by anti-p80NPM/ALK or ALK1 antibodies. Recently, some investigators including us asserted that these p80NPM/ALK or ALK1-positive(p80/ALK+) ALCLs represent a distinct genetic entity with occurrence in young patients and a favorable prognosis, and should be differentiated from the p80/ALK- tumors with the relatively aggressive clinical course. The p80/ALK+ lymphomas also revealed the characteristic morphology such as horseshoe-like, kidney-like or doughnut-like nuclei and frequent expression of EMA and cytotoxic molecules. However, these features are shared, though to a lesser degree, by other p80/ALK-negative lymphoid neoplasms. Indeed, it is indicated that cytotoxic ALCL cases may be either p80/ALK positive or negative, suggesting that the cytotoxicity and expression of p80/ALK are independent phenomena among the cases of ALCL of T- and null-cell type. Thus, several areas of disagreement and controversy that surround the diagnosis and categorization of ALCL remain.

Biomarkers, Tumor↗

Regional cerebral blood flow in the patients with depressive disorders.

Regional Cerebral blood flow (rCBF) and metabolism in major depression have been studied intently. Those studies are expected to reveal the mechanisms of the mood disorders, and also to give us valuable informations that the specific brain regions participating mood regulation. However, the data still have been inconsistent. In the present study we measured rCBF in patients with major depression and depressive state using xenon-CT CBF method. There is a tendencies that the rCBF values of normal control is the highest, and those of major depression is the lowest in most of the regions. The rCBF values in the patients with major depression are significantly lower than those in normal control in the right anterior frontal cortex, temporal cortex, putamen and thalamus. We also measured rCBF before and 90 minutes after giving calcium antagonist nilvadipine (4 mg, p.o.) in those subject. There is a tendency that nilvadipine increased in rCBF in normal control, however, it decreased in rCBF in major depression.

Adult↗

Biosynthesis of Vicia graminea lectin- and Vicia unijuga lectin-binding glycoproteins in human tumor and nontumor cells and an estimation of its epitope structure.

We investigated biosynthesis of Vicia graminea lectin (VGA)- and Vicia unijuga lectin (VUA)-binding (Vgu) glycoproteins, which are human malignant tumor-associated antigens, in cultured human tumor and non-tumor cells by pulse-labeling experiments with [35S]-methionine, followed by immunoprecipitation using immobilized VUA, SDS-PAGE and autofluorography. It was shown that Vgu glycoproteins synthesized by tumor cells were 15-30 times greater than those of non-tumor cells. It was also shown that about 40-70% of Vgu glycoproteins synthesized by non-tumor cells were secreted from the cells while more than 80% of the antigen synthesized by tumor cells was not secreted, and that Vgu glycoproteins consisted of multiple molecular species with the same epitope. To estimate the epitope structure of Vgu glycoproteins, in preliminary experiments we prepared sialoglycoproteins and/or sialoglycopeptides from purified human glycophorin A. Human glycophorins A(M) and A(N) (GPs-A(M) and A(N)) were treated with Clostridium perfringens neuraminidase to remove all sialic acid residues linked to carbohydrate chains, with Newcastle disease virus (NDV) to remove alpha2-3 linked sialic acid residues, and by Edman's degradation to eliminate N-terminal amino acid of GP-As. Partial or complete desialylation reactions resulted in disappearance of the reactivity of GP-A(M) and GP-A(N) with corresponding antisera and in appearance of reactivities with VUA and VGA. Elimination of N-terminal amino acid of GP-As also resulted in appearance of reactivities with VUA. These results show that sialoglycoproteins with similar serological properties of Vgu glycoprotein could be prepared from GP-As, and suggest that the epitope structure of Vgu glycoprotein may be related to the MN blood type-epitope structure and its sialic acid residues at N-terminal moiety of GP-As.

Amnion↗

[Cyclophosphamide-induced renal pelvic tumor--a case report].

We report a case of transitional cell carcinoma in the left renal pelvis, which occurred in a 24-year-old man. He had been treated with cyclophosphamide (CPM) for a period of 27 months for retroperitoneal rhabdomyosarcoma diagnosed at the age of 10. At first 1.2 g CPM had been given twice intravenously for 3 months, followed by oral administration of 41 g CPM for 23 months. Drip infusion pyelography revealed a filling defect in the left renal pelvis. A left renal pelvic tumor was strongly suspected on computerized tomography and magnetic resonance imaging. Left nephroureterectomy was then performed. Histological diagnosis of the left renal pelvic tumor was transitional cell carcinoma, grade 2, pT1N0M0. No recurrence was defected 17 months later. This case seems to be the second case of cyclophosphamide-induced upper urothelial carcinoma reported in Japan.

Adult↗

[Avascular necrosis of the femoral head caused by steroid treatment in neurosurgery].

Steroid induced avascular necrosis of the femoral head is a well known disease, but, there are few reports about the disease in neurosurgical patients. In the neurosurgical field, the use of steroids has become prevalent since the 1960's. Recently, the adverse effect of steroids and the limitation of its effect have been highlighted, but its use against neurosurgical diseases is still a common treatment to prevent cerebral edema or to counteract hypo-pituitarism caused by hypophyseal lesions. We reviewed 250 patients of avascular necrosis treated between 1985 and 1997 in our institute. Within these patients, 11 (4.4%) were treated with steroid during neurosurgical treatment. Six patients were treated for brain tumors near hypophyseal lesions, and 5 patients were treated for head injury or cerebro-vascular disease. It is concluded that total steroid dose over 5000 mg such as hydrocortisone may become a high risk for causing avascular necrosis of the femoral had in neurosurgical disease, and it may occur even with the supplemental steroid treatment against hypo-pituitarism. The onset is usually 2 or 3 years after the neurosurgical treatment, when neurosurgical care is no longer needed. Therefore, it tends to be ignored in the neurosurgical field. The treatments against avascular necrosis of the femoral head were femoral head osteotomy or conservative management, and good results were obtained. Early diagnosis and early treatment is essential. Further consideration concerning steroid treatment in neurosurgical patients may be required.

Anti-Inflammatory Agents↗

[Correlations of histologic classification with clinical features and prognosis in interstitial lung disease associated with collagen disease].

We studied 32 patients with interstitial pneumonia associated with collagen disease. All underwent surgical lung biopsy. Twenty-seven were histologically classified as follows: 8 with usual interstitial pneumonia (UIP), 10 with nonspecific interstitial pneumonia (NSIP), 6 with bronchiolitis obliterans organizing pneumonia (BOOP), and 3 with diffuse alveolar damage (DAD). Twenty-five of the patients were treated with corticosteroid but 4 (3 DAD, 1 NSIP) deteriorated rapidly and died within a month after lung biopsy. At the final follow-up, all 8 UIP patients were alive with residual respiratory impairment, whereas 6 NSIP and 4 BOOP patients had almost completely recovered. These findings suggested that histologic classification can be highly valuable to the therapeutic responsiveness and prognosis in cases of interstitial pneumonia associated with collagen disease.

Adult↗

[Sarcoidosis with primary acute cavitation exacerbated by bronchial asthma].

A 22-year-old woman complaining of blurred vision visited our hospital in March 1995 and was given a diagnosis of uveitis. Chest X-ray and computed tomographic (CT) films demonstrated bilateral hilar lymphadenopathy (BHL), diffuse granular shadows in both lung fields, and a cavity with a thin, smooth wall in the right upper lung field. Because histopathologic findings from transbronchial lung biopsy specimens of the lung and cavity tissues disclosed sarcoid granuloma, the diagnosis was sarcoidosis with primary cavitation, which is very rare for this disease. Although BHL disappeared without medication, in November the patient experienced dyspnea due to attacks of bronchial asthma that had been in remission for a long period. Treatment with inhalation of becromethazone propionate markedly alleviated her symptoms. In May 1998, follow-up chest CT films demonstrated that the cavity had disappeared. This case suggested that sarcoidosis leads to a deterioration of asthma control, a conclusion supported by previous reports.

Adult↗

[Two cases of idiopathic membranous nephropathy with focal and segmental glomerulosclerotic lesions in which renal function progressively deteriorated].

Previous reports have clarified that focal and segmental glomerulosclerosis(FSGS) appearing in membranous nephropathy(MN) is associated with a poorer prognosis than that of MN without FSGS. However, the etiology and pathogenesis of such FSGS lesions may show substantial individual differences. In some patients, hemodynamic alterations secondary to hypertension and vascular disorders seem to play a crucial role in the development of such FSGS lesions. In such instances, steady regulation of blood pressure might slow down further progression of FSGS lesions. Here we describe two cases of biopsy-proven MN with FSGS. Case I was a 44-year-old man who had shown massive proteinuria with hematuria at the age of 39 years. Renal biopsy specimens obtained at the age of 40 and 41 years showed MN without FSGS and MN with FSGS, respectively. His blood pressure control was fairly good throughout the course. Although he was on a steroid, an immunosuppressant, a low protein diet, and an ACE inhibitor, his renal function declined in 5 years. Case 2 was a 61-year-old woman who showed nephrotic syndrome at the age of 39 years. A renal biopsy specimen obtained at the age of 58 years showed MN with FSGS and remarkable atherosclerotic changes of the interlobular arteries. Her blood pressure control was rather poor throughout the course. Her renal function gradually declined over 22 years. Since parts of the FSGS lesions of the second case may have been caused by hypertension, it is tempting to speculate that day-to-day control of blood pressure could improve the long-term prognosis. We believe that, at least in some patients of MN with FSGS, careful management may lead to a more favorable course of decline in renal function.

Adult↗

Reducing the volume of polyethylene glycol electrolyte lavage solution to less than 2 liters for bowel preparation.

Smaller volumes of polyethylene glycol electrolyte lavage solution (PEG), an oral whole-bowel irrigation solution employed in colorectal preparation, were given to patients to decrease the discomfort associated with pretreatment. Comparison was made between groups receiving standard and modified preparations. A total of 68 patients (gastrointestinal surgery: 55; total colonoscopy: 13) were enrolled in the study. The mean volume of PEG used was significantly smaller in the modified than in the standard preparation (1,694 ml vs. 2,735 ml, p<0.01). In addition, the mean PEG administration period was significantly shorter for the modified preparation (183 min vs. 237 min, p<0.05). However, the mean PEG excretion time and the number of bowel movements were not significantly different between the two groups. There was also no significant difference between the two groups in terms of the efficacy, safety, usefulness, or tolerability of the preparations. These results suggest that it is possible to reduce the PEG volume by more than 1 L to alleviate patient discomfort without a significant loss of efficacy. The modified method is useful for preparing the large bowel for either gastrointestinal surgery or total colonoscopy.

Colonoscopy↗

[Assessment of colorectal cancer patients exhibiting bilobular multiple hepatic metastases].

We assessed 23 patients who underwent surgical therapy of hepatectomy or microwave coagulation therapy (MCT) for bilobular multiple hepatic metastatic foci following curative resection of the primary lesion of colorectal cancer. Hepatectomy was the first surgical therapy for 10 patients, and 6 of them received combined intra-arterial chemotherapy. All 13 patients in the MCT group received intra-arterial chemotherapy, and 8 of them underwent combined hepatectomy. The two-year survival rate of the hepatectomy group, classified according to the first surgical therapy, was 40% against 52% in the MCT group. In comparison with the H2 (2-5 foci) patients in the hepatectomy group, there were 7 H2 patients in the MCT group, and the two-year survival rate of these 7 patients was 50%. No significant difference was observed between hepatectomy and the MCT as the first surgical therapy. The survival rates of the 5 patients who received treatment for recurrence after the first surgery and of the 18 patients without any recurrence treatment were 80% and 40%, respectively. No significant difference existed between the two groups, but a p value of 0.06 was noted. MCT was considered to be useful local therapy for cancer as the first therapy and as a therapy following recurrence.

Antineoplastic Agents↗

[Transcatheter arterial chemo-embolization using degradable starch microspheres (DSM) markedly effective for post-hepatectomy intra-hepatic recurrence in a patient with cholangioma].

Transcatheter arterial chemo-embolization (TACE) using degradable starch microspheres (DSM) was performed for multiple recurrence after hepatectomy in a patient with cholangiocarcinoma. The patient was a 68-year-man. He received treatment for hepatitis type C starting in 1996 at a nearby hospital. In November 1997, an increased AFP level was noted and a CT scan of the abdomen revealed an abnormal shadow in the liver. On May 21, 1998, imaging results led to the diagnosis of cholangiocarcinoma or a mixed type of hepatocellular carcinoma with cholangioma. Hepatic S7 sub-sequential resection was performed. The lesion was found to be a tumor-forming type, measuring 2.2 x 2.0 cm in diameter, diagnosed histopathologically as cholangiocarcinoma, tw (-), but Stage III since a nodule suggesting intrahepatic metastasis was noted in the cut surface of the resected liver. CT scan after a month revealed multiple metastatic lesions in the liver. TACE was performed by administering 450 mg of DSM, 10 mg of MMC and 30 mg of FARM, given in three divided doses on October 30, 1998, and February 9, 1999, according to Seldinger's method. A CT scan on January 31, 2000 revealed nearly complete remission of the hepatic SOL. Accordingly, TACE was considered to be useful therapy in combination with DSM, MMC and FARM for intrahepatic recurrence of cholangiocarcinoma.

Aged↗

[Three long surviving patients with gastric cancer metastasizing to the liver under interdisciplinary therapy].

In 30 patients with gastric cancer metastasizing to the liver over the past 15 years at our hospital the primary foci in the stomach could be resected in a curative manner. The authors report herein three long surviving patients in this series. [Case 1] A 49-year-old male. Distal gastrectomy was performed in November 1984. Metastasis to the liver occurred in June 1986. The right lobe of the liver was resected in November 1987 after transcatheter arterial embolization (TAE). Although hepatic arterial infusion chemotherapy was conducted, the cancer metastasized to the whole body, and the patient died in December 1991. [Case 2] A 65-year-old female. Distal gastrectomy was performed in July 1994. The left hepatic lobe and segment 5 in the right lobe were resected in June 1995. Although TAE was performed six times starting in December 1996, the patient died of hepatic failure in July 1999. [Case 3] A 73-year-old male. This patient simultaneously received distal gastrectomy and extended resection of the posterior hepatic segments in September 1997. Cancer recurred in the remaining liver in July 1998. Although microwave coagulation therapy (MCT) and TAE were performed, the patient died of hepatic failure in January 2000. In these patients who survived for a long period, the primary focus was well-differentiated adenocarcinoma under sufficient local control with metastasis limited to the nearest regional lymph nodes (group 1 lymph nodes). The patients could undergo interdisciplinary therapy, including hepatectomy, MCT, TAE, and hepatic arterial infusion chemotherapy.

Adenocarcinoma↗

Molecular cloning of a novel CC chemokine, interleukin-11 receptor alpha-locus chemokine (ILC), which is located on chromosome 9p13 and a potential homologue of a CC chemokine encoded by molluscum contagiosum virus.

Molluscum contagiosum virus (MCV) encodes a CC chemokine MC148R which is likely to have been acquired from the host. By a homology search employing MC148R as a probe, we have identified a novel CC chemokine whose gene exists next to the IL-11 receptor alpha (IL-11Ralpha) gene in both humans and mice. Thus, this chemokine maps to chromosome 9p13 in humans where IL-11Ralpha has been assigned. We term this novel chemokine IL-11Ralpha-locus chemokine (ILC). ILC has the highest homology to MC148R among the known human CC chemokines. Furthermore, ILC is strongly and selectively expressed in the skin where infection of MCV also takes place. Thus, ILC is likely to be the original chemokine of MC148R.

Amino Acid Sequence↗

Interleukin-10 (IL-10) selectively enhances CIS3/SOCS3 mRNA expression in human neutrophils: evidence for an IL-10-induced pathway that is independent of STAT protein activation.

We have recently shown that, in human neutrophils, interleukin-10 (IL-10) fails to induce specific DNA-binding activities to the gamma-interferon response region (GRR), a regulatory element located in the FcgammaRI gene promoter, which is required for transcriptional activation by IL-10 and interferon gamma (IFNgamma) in monocytic cells. In this study, we report that IL-10 is also unable to induce the binding of STAT1 or STAT3 to the serum-inducible element (hSIE/m67), despite the fact that both proteins are expressed in neutrophils. Whereas IFNgamma and granulocyte colony-stimulating factor (G-CSF) are efficient inducers of STAT1 and STAT3 tyrosine phosphorylation in polymorphonuclear neutrophils (PMN), IL-10 fails to trigger STAT1 and STAT3 tyrosine and serine phosphorylation, therefore explaining its inability to induce the FcgammaRI expression in these cells. By contrast, we demonstrate that IL-10 alone represents an efficient stimulus of CIS3/SOCS3 mRNA expression in neutrophils. CIS3/SOCS3 belongs to the recently cloned cytokine-inducible SH2-containing protein (CIS) gene family (which also includes CIS1, CIS2, CIS4, CIS5, and JAB) that is believed to be, at least in part, under the control of STAT transcription factors and whose products are potential modulators of cytokine signaling. Moreover, IL-10 synergizes with lipopolysaccharide (LPS) in upregulating CIS3/SOCS3 mRNA expression in PMN through a mechanism that involves mRNA stabilization. In contrast to CIS3/SOCS3, mRNA transcripts encoding other family members are unaffected by IL-10 in neutrophils. Finally, transfection of CIS3/SOCS3 in murine M1 myeloid cells suppresses LPS-induced growth arrest, macrophage-like differentiation, and nitric oxide synthesis, but not IL-6 mRNA expression. Collectively, our data suggest that, in neutrophils, the activation of STAT1 and STAT3 phosphorylation is neither required for CIS3/SOCS3 induction by IL-10 nor involved in the regulatory effects of IL-10 on cytokine production.

Animals↗

A novel gene, MALT1 at 18q21, is involved in t(11;18) (q21;q21) found in low-grade B-cell lymphoma of mucosa-associated lymphoid tissue.

The t(11;18) (q21;q21) translocation is a characteristic chromosomal aberration in low-grade B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) type. We previously identified a YAC clone y789F3, which includes the breakpoint at 18q21 in a MALT lymphoma patient. BAC and PAC contigs were constructed on the YAC, and BAC 193f9 was found to encompass the breakpoint region. In the present study, we further narrowed down the breakpoint region at 18q21 in five MALT lymphoma patients by means of FISH and Southern blot analyses using the plasmid contig constructed from BAC 193f9. The breakpoints at 18q21 in three of the five MALT lymphoma patients were found to be clustered approximately within the 20 kb region. By using exon amplification and cDNA library screening, we identified a novel cDNA spanning the breakpoint region that exhibited aberrant mRNA signals in four of the five MALT lymphoma patients. The nucleotide sequence predicted an 813 amino acid protein that shows significant sequence similarity to the CD22beta and laminin 5 alpha3b subunit. We refer to the gene encoding this transcript as MALT1 (Mucosa-Associated Lymphoid Tissue lymphoma translocation gene 1). The alteration of MALT1 by translocation strongly suggests that this gene plays an important role in the pathogenesis of MALT lymphoma.

Amino Acid Sequence↗

Molecular cloning of a novel human CC chemokine (Eotaxin-3) that is a functional ligand of CC chemokine receptor 3.

Previously, we mapped the novel CC chemokine myeloid progenitor inhibitory factor 2 (MPIF-2)/eotaxin-2 to chromosome 7q11.23 (Nomiyama, H., Osborne, L. R., Imai, T., Kusuda, J., Miura, R., Tsui, L.-C., and Yoshie, O. (1998) Genomics 49, 339-340). Since chemokine genes tend to be clustered, unknown chemokines may be present in the vicinity of those mapped to new chromosomal loci. Prompted by this hypothesis, we analyzed the genomic region containing the gene for MPIF-2/eotaxin-2 (SCYA24) and have identified a novel CC chemokine termed eotaxin-3. The genes for MPIF-2/eotaxin-2 (SCYA24) and eotaxin-3 (SCYA26) are localized within a region of approximately 40 kilobases. By Northern blot analysis, eotaxin-3 mRNA was constitutively expressed in the heart and ovary. We have generated recombinant eotaxin-3 in a baculovirus expression system. Eotaxin-3 induced transient calcium mobilization specifically in CC chemokine receptor 3 (CCR3)-expressing L1.2 cells with an EC(50) of 3 nM. Eotaxin-3 competed the binding of (125)I-eotaxin to CCR3-expressing L1.2 cells with an IC(50) of 13 nM. Eotaxin-3 was chemotactic for normal peripheral blood eosinophils and basophils at high concentrations. Collectively, eotaxin-3 is yet another functional ligand for CCR3. The potency of eotaxin-3 as a CCR3 ligand seems, however, to be approximately 10-fold less than that of eotaxin. Identification of eotaxin-3 will further promote our understanding of the control of eosinophil trafficking and other CCR3-mediated biological phenomena. The strategy used in this study may also be applicable to identification of other unknown chemokine genes.

Amino Acid Sequence↗

An activation-responsive element in single C motif-1/lymphotactin promoter is a site of constitutive and inducible DNA-protein interactions involving nuclear factor of activated T cell.

Single C motif-1 (SCM-1)/lymphotactin is a C-type chemokine whose expression is activation dependent, cyclosporin A sensitive and restricted to CD8+ T cells, double-negative thymocytes, gammadelta-type T cells, and NK cells. In humans, there are two highly homologous genes encoding SCM-1alpha and SCM-1beta. Here we examined the regulatory mechanism of the SCM-1 genes. The luciferase reporter gene under the control of the 5' flanking region of 0.7 kb was strongly induced upon activation with anti-CD3 or PHA plus PMA only in SCM-1-producer T cell lines through a cyclosporin A-sensitive mechanism. An element termed E1 located at -108 to -95 nt relative to the major transcription start site was found to be critical for the promoter activity. In electrophoretic mobility shift assays using the E1 oligonucleotide as probe, nuclear extracts from unstimulated T and B cell lines formed a constitutive complex termed complex I, while nuclear extracts from stimulated SCM-1-producer T cell lines formed a higher mobility complex termed complex II with a concomitant decrease in complex I. The shift from complex I to complex II seen only in SCM-1-producer T cell lines upon activation was completely suppressed by cyclosporin A. Both complexes were critically dependent on the NF-AT core sequence TTTCC in the E1 element and were partially supershifted by anti-NF-ATp. One-hybrid assays in yeast isolated NF-ATp as an E1 binding protein, and transfection of NF-ATp into T and B cell lines strongly enhanced the activation-dependent SCM-1 promoter activity. Collectively, a unique mechanism involving NF-ATp appears to regulate the cell type-specific and activation-dependent expression of the SCM-1 genes.

5' Untranslated Regions↗