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Biomedical subjects

K Shimizu

Publications and source records attributed to K Shimizu.

At least 559 records · Page 31Linked to original sources

Geographic variation in mortality among individuals with youth-onset diabetes mellitus across the world. DERI Mortality Study Group. Diabetes Epidemiology Research International.

The aim of this study was to evaluate the geographic variation in mortality among individuals with youth-onset insulin-dependent diabetes mellitus (IDDM) across the world. The study was based on the currently available IDDM incidence and mortality data. Mortality data for diabetes in the 0-24 year age group were obtained from the World Health Organization (WHO) statistics. The mortality rates were adjusted for the frequency of occurrence of IDDM and dividing the mortality rates by the IDDM incidence rates which were obtained from the WHO DiaMond project. There was a more than 10-fold geographic variation in mortality between the developed countries and Eastern European populations. The areas with the highest mortality rates were located in Japan, Eastern Europe and Russia. The areas having the best outcome associated with IDDM were Northern Europe, Central Europe, and Canada. An ecological study demonstrated a relationship between the incidence-adjusted mortality (estimated case-fatality) with IDDM incidence itself (Spearman's correlation coefficient = 0.45) as well as infant mortality and life expectancy at birth. These data demonstrated the possibility of an enormous geographic variation in mortality of youth-onset diabetic patients even in developed countries. It is important to note that these excess deaths are potentially preventable. The ecological study also suggested that the mortality differences may be in part related to overall and diabetes related care.

Adolescent↗

Characterization of the intron-containing citrate synthase gene from the alkanotrophic yeast Candida tropicalis: cloning and expression in Saccharomyces cerevisiae.

Citrate synthase, an essential enzyme of the tricarboxylic acid cycle in mitochondria, was purified from acetate-grown Candida tropicalis. Results from SDS-PAGE and gel filtration showed that this enzyme was a dimer composed of 45-kDa subunits. A citrate synthase cDNA fragment was amplified by the 5'-RACE method. Nucleotide sequence analysis of this cDNA fragment revealed that the deduced amino acid sequence contained an extended leader sequence which is suggested to be a mitochondrial targeting signal, as judged from helical wheel analysis. Using this cDNA probe, one genomic citrate synthase clone was isolated from a yeast lambdaEMBL3 library. The nucleotide sequence of the gene encoding C. tropicalis citrate synthase, CtCIT, revealed the presence of a 79-bp intron in the N-terminal region. Sequences essential as yeast splicing motifs were present in this intron. When the CtCIT gene including its intron was introduced into Saccharomyces cerevisiae using the promoter UPR-ICL, citrate synthase activity was highly induced, which strongly indicated that this intron was correctly spliced in S. cerevisiae.

Amino Acid Sequence↗

A randomized study comparing VMCP and MMPP in the treatment of multiple myeloma.

PURPOSE: To compare VMCP, a multidrug combination chemotherapy comprising vincristine (VCR), melphalan (MPH), cyclophosphamide (CPM) and prednisolone (PSL), with MMPP comprising MPH, ranimustine (MCNU), procarbazine, and PSL as induction, to elucidate the value of alternating combination chemotherapy, and to search for an appropriate maintenance therapy in multiple myeloma. METHODS: At 16 institutions in the Nagoya City area, we carried out a randomized trial of VMCP versus MMPP as the initial treatment. Patients who were refractory or resistant to the initial therapy were crossed over into the other arm (crossover trial). For patients who achieved a partial response (PR) or a minor response (MR) and in whom the paraprotein level ceased to decrease, the maintenance therapy was randomized either to an MPH/PSL combination (MP) or to alternating combination therapy (AT) with VMCP and MMPP. RESULTS: In the 94 evaluable patients of the 111 enrolled, the response rate (PR rate) was 27.7% (13/47) in the VMCP arm and 44.7% (21/47) in the MMPP arm (P = 0.0859). The crossover trial resulted in a PR rate of 15.8% (3/19) for the VMCP-->MMPP crossover and 14.3% (2/14) for the MMPP-->VMCP crossover. The median survival time was 23.4 months for those initially begun in the VMCP arm and 24.9 months for those in the MMPP arm, showing a tendency for better survival during a follow-up of 2-6 years with MMPP treatment, but without statistical significance. The survival time of patients with progressive disease was significantly shorter than that of patients with PR, MR or no change (NC). However, there was no significant difference in the survival rate among those who achieved PR, MR, or NC. As to the maintenance therapy, there was no significant difference in survival between MP therapy and AT. Patients who reached a plateau phase survived significantly longer than those who did not. Except for six cases of grade 3 or 4 neurotoxicity in the VMCP arm, there was no significant difference in the hematologic or gastrointestinal toxicity between the two arms. CONCLUSIONS: We conclude that VMCP is less effective for myeloma than MMPP as the induction treatment, that alternating noncrossresistant chemotherapeutic combinations do not offer an advantage in multiple myeloma, and that patients who reach a plateau phase have a significantly longer survival time.

Adult↗

White dot fovea.

PURPOSE: To describe a newly identified clinical entity tentatively named white dot fovea. METHODS: We examined by scanning laser ophthalmoscopy 58 eyes of 30 patients (mean age, 64 years) who had white dots in the fovea (anatomically defined as the foveola) simulating macular hole. In addition, the retinal surfaces of 30 autopsy eyes from donors aged 70 years or older were observed by scanning electron microscopy. RESULTS: White dot fovea was bilateral in 28 of 30 patients (93%). It was characterized by the presence of numerous white dots on the foveal surface distributed either diffusely or along the foveal margin, forming a gray ring. There was no subjective symptom or visual disturbance. The condition was best seen by a scanning laser ophthalmoscope using argon blue laser as the light source. The white dots numbered from 100 to 300 per eye. Each dot was approximately 5 microns in diameter. Scanning electron microscopy showed foveal granules simulating the white dots in five of 30 autopsy eyes (17%). The granules had multiple protrusions with cilia-like structures resembling glial cells. This glia-like structure seemed to be a counterpart of clinically observed white dot fovea. CONCLUSION: White dot fovea is a new, frequent, and apparently innocuous clinical entity. It merits due attention in the differential diagnosis of macular holes.

Aged↗

Ciliary body and choroidal detachment after laser photocoagulation for diabetic retinopathy. A high-frequency ultrasound study.

OBJECTIVE: The purpose of the study is to clarify the manifestation of the ciliary body after retinal photocoagulation for diabetic retinopathy. DESIGN: Ultrasound biomicroscopy (UBM) was applied to obtain the tomographic features of the anterior ocular segment. PARTICIPANTS: Twenty-one eyes of 17 consecutive patients with diabetic retinopathy were included in this study. INTERVENTION: These eyes were treated by panretinal photocoagulation divided in four sessions. In the first session, the nasal quadrant of the fundus was treated with argon or dye (590 nm) laser totaling 208 to 331 spots per eye. MAIN OUTCOME MEASURES: The eyes were examined by UBM before, immediately after, 3, and 7 days after the first session of photocoagulation. RESULTS: Three days after photocoagulation, ciliochoroidal detachment was observed in 19 eyes (90%). The detachment was present along the whole circumference. The ciliary detachment was most prominent in the pars plana in 19 eyes and extended to the pars plicata in 9 eyes. It spontaneously had disappeared 7 days after photocoagulation. CONCLUSIONS: Ciliochoroidal detachment was a very frequent feature after sector photocoagulation in diabetic eyes. Although this complication was asymptomatic and transient so far, this potential hazard merits due attention in the planning of panretinal photocoagulation in diabetic eyes.

Adult↗

A case of pulmonary ossified adenocarcinoma with marked osteoplastic bone metastasis.

We report the case of a 53-year-old man suffering from a pulmonary adenocarcinoma with ossification and diffuse metastatic osteoplastic lesions throughout the skeletal system. This is a rare condition in lung carcinomas. Radiographs of the chest and bones demonstrated mineral densities in the primary tumor and multiple expansive osseous lesions with a diffuse sclerotic pattern resembling multiple bone metastases from prostatic carcinoma.

Adenocarcinoma↗

Thrombotic microangiopathy associated with alpha-interferon therapy for chronic myelocytic leukemia.

A 31-year-old man diagnosed as having chronic myelocytic leukemia (CML) developed renal insufficiency with nephrotic-range proteinuria during alpha-interferon (IFN) therapy for CML. A renal biopsy specimen showed remarkable thrombotic microangiopathic lesions resembling those of hemolytic-uremic syndrome. The patient had papules on both lower legs, and a cutaneous biopsy showed similar microangiopathic lesions in dermal and subcutaneous vessels. Although discontinuation of IFN and initiation of prednisolone therapy resulted in resolution of proteinuria, renal insufficiency persisted. These findings suggest that long-term IFN therapy can induce late-onset thrombotic microangiopathy in systemic microvessels.

Adult↗

A difference in responsiveness of isolated hepatic artery, aorta, portal vein and vena cava of pig to flavin adenine dinucleotide including liver extract.

1. Tension of isolated hepatic artery, aorta, portal vein and vena cava of pigs was measured isometrically to study the mode of action of flavin adenine dinucleotide, including liver extract (FADLE). 2. FADLE showed concentration-dependent relaxation of norepinephrine contraction in the hepatic artery, but FADLE had little influence on the aorta, portal vein and vena cava contracted by norepinephrine (NE). 3. In Ca(2+)-free solution, FADLE-induced relaxation in both the hepatic artery and aorta contracted by NE was significantly reduced, and its reduction was greater in the hepatic artery than in the aorta. Furthermore, extracellular Ca2+ dependence of norepinephrine-induced contraction was much larger in the hepatic artery than in the aorta. 4. Results suggest that FADLE shows regional variations in vasorelaxation through the alteration of Ca2+ movement by the cell, and that this may reflect one of the mechanisms in its ability to increase blood flow in hepatic tissue.

Animals↗

Hepatic hilar inflammatory pseudotumor mimicking cholangiocarcinoma with cholangitis and phlebitis--a variant of primary sclerosing cholangitis?

Inflammatory pseudotumor (IPT) of the liver is rare. We present a case of hepatic IPT mimicking cholangiocarcinoma in which the tumor was located at the left porta hepatis. The patient was a 64-year-old man in whom abnormal liver function test results had been noted incidentally during an annual health checkup in 1993: the patient declined to go to the hospital for further examination. At the annual health checkup the following year, abnormal liver function test results were noticed again, and this time he did go to a hospital, where a hepatic mass was found. Laboratory test results were unremarkable. Based on the location of the lesion and the findings of a variety of imaging modalities, such as ultrasound and computed tomography examination, the lesion was preoperatively diagnosed as hilar cholangiocarcinoma and was surgically resected. Pathologic examination of the resected lesion, however, revealed that it was not a true tumor but an inflammatory pseudotumor with marked destructive and sclerosing cholangitis mimicking primary sclerosing cholangitis (PSC) and obliterative phlebitis. Since the location and features of the tumor in the present case are very pertinent to the relationship between IPT and PSC, we describe its clinical and histologic features and discuss the findings in relation to PSC in the context of our literature review.

Bile Duct Neoplasms↗

Effect of a glutamine-enriched diet on small bowel allograft during immunosuppressive therapy.

The effect of an orally administered glutamine-enriched elemental diet was examined following orthotopic small bowel allotransplantation using Brown Norway rats as donors and Lewis rats as recipients. The recipients was treated with FK 506 and randomized to receive glutamine-free elemental enteral diet solution (glutamine-free group), glutamine-enriched elemental diet solution containing 7500 mg of glutamine per 100 g diet (glutamine-enriched group) or standard chow (chow group) ad libitum for 7 d. There were no histological changes due to resection. Weight loss in the glutamine-enriched group was significantly less than that of the chow group. Both plasma glutamine levels and the ratio of glutamine to total amino acids in the homogenate of the graft mucosa of the glutamine-enriched group were significantly higher than those of the glutamine-fee group. Villous height and crypt depth were significantly decreased in the glutamine-free group. The BrdU labeling index in the graft epithelium and alkaline phosphatase activity in the homogenate of the graft mucosa of the glutamine-enriched group were significantly higher than those of the glutamine-free group. Therefore, orally administered glutamine-enriched elemental diet appears to promote the regeneration and differentiation of the graft mucosa following small bowel allotransplantation.

Aging↗

Interleukin-1 beta enhances and tumor necrosis factor-alpha inhibits bone morphogenetic protein-2-induced alkaline phosphatase activity in MC3T3-E1 osteoblastic cells.

The modulatory effects of interleukin (IL)-1 beta and tumor necrosis factor (TNF)-alpha on bone morphogenetic protein (BMP)-2- and -4-induced alkaline phosphatase (ALP) activity were examined in cultures of mouse MC3T3-E1 osteoblastic cells. Both BMP-2 and -4 significantly induced ALP in these cells. IL-1 beta alone had no effect on ALP activity, but it significantly enhanced BMP-2- and -4-induced ALP activity. TNF-alpha suppressed the induction of ALP by BMP-2 or -4. The results suggest that the action of BMP on osteogenic differentiation may be regulated by such immuno/inflammatory cytokines as IL-1 beta and TNF-alpha.

3T3 Cells↗

Gene delivery by HVJ-liposome in the experimental gene therapy of murine glioma.

We investigated the delivery of foreign genes into mouse glioma cells in vivo using hemagglutinating virus of Japan (HVJ)-liposomes, which are coated by Sendai virus envelope protein. HVJ-liposomes, containing lacZ gene or herpes simplex virus thymidine kinase (HSVtk) gene-bearing plasmid DNA were applied in the meningeal gliomatosis (MG) mouse model system. Highly efficient delivery was observed in disseminated glioma cells, and 80% of MG mice expressing the HSVtk gene were cured by treatment with ganciclovir. These results suggest that this novel gene delivery system may be applicable for the in vivo gene therapy of human malignant glioma.

Animals↗

CBFA2, frequently rearranged in leukemia, is not responsible for a familial leukemia syndrome.

We have identified a family with an autosomal dominant platelet disorder with a predisposition for developing myeloid malignancies and have previously demonstrated linkage of this trait to chromosome 21q22.1-22.2. The nearest flanking markers, D21S1265 and D21S167, define the familial platelet disorder (FPD) critical region at a genetic distance of approximately 15.2 centimorgans and physical distance of approximately 6 megabases. This locus is of particular interest as it has previously been implicated in the pathogenesis of acute myelogenous leukemia (AML) and acute lymphoblastic leukemia (ALL) through the (8;21), (3;21) and (12;21) chromosomal translocations. In each of these cases, the CBFA2 gene is rearranged. As well, there is a potential association of this locus with the hematologic abnormalities seen in Down syndrome (trisomy 21). To identify the mutant gene in this pedigree, a positional cloning strategy has been undertaken. Several candidate genes map to this locus including: CBFA2, IFNAR1, IFNAR2, CRFB4, GART, SON, KCNE1, SCL5A3 and ATP50. CBFA2, as well as IFNAR1 and CRFB4, were the focus of initial mutational analysis efforts. In this report, we exclude CBFA2 as a candidate by Northern and Southern blotting, RNase protection, single-strand conformational polymorphism (SSCP), direct sequencing and gel-shift analysis. Exons of the IFNAR1 and CRFB4 genes were also analyzed by SSCP and demonstrated no evidence of mutation. SSCP analysis identified a new polymorphism in the second exon of the CRFB4 gene and confirmed a previously described polymorphism in the fourth exon of IFNAR1. Efforts are currently underway to delimit further the FPD critical region and to analyze the other known candidate genes, as well as novel candidate genes, which map to this locus.

Core Binding Factor Alpha 2 Subunit↗

Multiple thoracic disc herniations: case report and review of the literature.

The incidence of intervertebral disc herniation in the thoracic region of the spine is much less than in the cervical or lumbar areas, and multiple thoracic disc herniations are rare. We described a 33-year-old man with two-level thoracic disc herniation, who exhibited features of spinal cord compression. Magnetic resonance imaging and computed tomographic myelography demonstrated anterior compression of the spinal cord due to disc herniation at T4/5 and T7/8 levels. Through an anterolateral approach, these discs were removed and interbody fusion was performed using autogenous bone grafts. Excellent results were obtained.

Adult↗

Genetic analysis of 8;21 chromosomal translocation without AML1 gene involvement in MDS-AML.

We have investigated a case of acute myelocytic leukaemia derived from myelodysplastic syndrome (MDS-AML) with an 8;21 translocation. In this case the AML1/MTG8 (ETO) fusion transcript was not detected by reverse transcriptase-polymerase chain reaction (RT-PCR), and the rearrangement of the AML1 gene locus was not detected by Southern blot nor pulse field gel electrophoresis (PFGE) analyses using specific probes for the AML1 gene. Fluorescence in-situ hybridization (FISH) study using cosmid probes for 21q22 revealed that the breakpoint of 21q22 was telomeric to the AML1 gene locus and centromeric from D21S259, 351, 3421 loci. This is the first report concerning the t(8;21)(q22;q22) carrying AMLs (de novo AML, MDS-AML and therapy-related AML) to show that the breakpoint at 21q22 is located outside the AML1 gene locus. It is also noteworthy that the cell-surface antigen expression pattern of the bone marrow (BM) blasts was changed from CD7+ CD2+ CD13+ CD33+ CD19- CD11b+ CD14+ CD36+ to CD7- CD2- CD13+ CD19+ CD11b- CD14- CD33+ CD34+ CD36- CD56+ during leukaemic progression, and the pattern in leukaemic phase was similar to the characteristic phenotype of de novo AML cases with t(8;21), when the AML1/MTG8 fusion transcripts are always detected by RT-PCR.

Blotting, Southern↗

The most frequent aminoglycoside resistance mechanisms--changes with time and geographic area: a reflection of aminoglycoside usage patterns? Aminoglycoside Resistance Study Groups.

The aminoglycoside resistance mechanisms revealed by two surveys in Europe and other countries have been compared to those revealed in earlier studies. Mechanisms have become more complex in all bacterial groups. In Providencia, Serratia, Pseudomonas, Acinetobacter, and Staphylococcus species isolates, genus-specific mechanisms were very common, and it was not possible to see differences between different geographic areas. In other Enterobacteriaceae, the increasing complexity of mechanisms was most often caused by combinations of gentamicin-modifying enzymes with AAC(6')-I, which acetylates amikacin but not gentamicin. The occurrence of these combinations varied by geographical region and among hospitals. The frequency of these combinations correlated with aminoglycoside usage in either the geographical regions or in individual hospitals. These broad-spectrum combinations occurred most frequently in Citrobacter, Enterobacter, and Klebsiella species but also occurred in Escherichia, Morganella, Proteus, Salmonella, and Shigella species. Often the only clinically available aminoglycoside that retained its normal activity was isepamicin.

Acinetobacter↗

Hypoxaemia in patients with hyperventilation syndrome.

We assessed 12 patients with hyperventilation syndrome (HVS) who had experienced hypoxaemia (PaO2 < 60 Torr or SaO2 < 90%) despite the lack of any other organic disease and variability in their blood gas data. Hypoxic and hypercapnic ventilatory responses were measured in nine. Eight of the 12 patients had been referred from other hospitals to our institution for hypoxaemia of unknown origin. Mean PaO2 (n = 12) at rest (non-attack stage) was 87.3 +/- 7.5 Torr (mean +/- SD). Their (n = 9) hypoxic (-0.53 +/- 0.32 l/min/%; range 0.12-0.99) and hypercapnic (2.01 +/- 0.76 l/min/Torr; range 0.69-3.17) ventilatory responses were both within the normal range in our laboratory. The patients with HVS had variable blood gas data, and some of them also exhibited hypercapnia (PaCO2 > 45 Torr). Clinicians who treat patients with HVS should be aware of the possibility of hypoxaemia, even when ventilatory responses are normal. Physicians should also consider HVS as a diagnosis when treating patients with hypoxaemia of unknown origin.

Adult↗

SPECT with In-111 autologous platelets to detect residual splenic tissue in two patients with relapsed thrombocytopenia.

In two patients with relapsed thrombocytopenia, the authors used SPECT with In-111 labeled autologous platelets to identify residual splenic tissue after splenectomy. One case involved a previously splenectomized patient with idiopathic portal hypertension, while the other had relapsed chronic idiopathic thrombocytopenic purpura (ITP). In both patients, SPECT showed a higher In-111 uptake in the splenic tissues compared with planar images. In the patient with ITP, a small accessory spleen had been overlooked on abdominal CT because of post-operative changes, but it was identified by superimposition of SPECT/CT images. These cases indicate that In-111 platelet SPECT is useful in detecting and localizing residual accessory splenic tissue associated with relapsed thrombocytopenia.

Adult↗