Lipoprotein(a) as a coronary risk factor in Japanese patients with Type II (non-insulin-dependent) diabetes mellitus. Relation with apolipoprotein(a) phenotypes.
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Biomedical subjects
Publications and source records attributed to Y Yoshida.
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Although resistance exercise training appears to increase bone mineral density in the long term, a single bout of resistance exercise could paradoxically induce bone homeostasis disturbance, secondary to metabolic acidosis. To examine this, we obtained fasting blood and 24-hour urine samples from untrained male subjects for 5 subsequent days (control day, exercise day, and three post-exercise days), and investigated the effects of a single bout of resistance exercise on urinary calcium excretion and bone metabolism as indicated by sensitive biomarkers of bone formation and resorption. After an intense bout of resistance exercise, blood and urine became more acidic and renal net acid excretion significantly increased by 44% on the exercise day. Urinary calcium excretion significantly increased by 48% on the exercise day. Plasma procollagen type-I C-terminal concentration significantly decreased by 12% on the next day of the exercise and serum bone-specific alkaline phosphatase activity also significantly decreased by 13% and 9% on days 2 and 3, respectively, after the exercise. There was no significant change in serum osteocalcin concentration. Serum tartrate-resistant acid phosphatase activity significantly decreased by 15% on the day after the exercise and urinary deoxypyridinoline excretion decreased by 22% and 27% on days 1 and 3, respectively, after the exercise. These results suggest that the early response of bone to a bout of resistance exercise in untrained individuals was transient decreases in bone formation and resorption, whereas urinary calcium excretion increased.
PURPOSE: To examine the pharmacokinetic relationships between humans and monkeys, we studied the disposition of 7-ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxycamptothecin (CPT-11) and its active metabolite, 7-ethyl-10-hydroxycamptothecin (SN-38), in rhesus monkeys. METHODS: CPT-11 was administered to a total of six monkeys at doses of 3, 7, 15 and 25 mg/kg by intravenous infusion for 10 min and plasma concentrations and pharmacokinetic parameters of CPT-11 determined. RESULTS: Maximum plasma concentrations at 25 mg/kg reached around 10000 ng/ml, and dropped to 500 ng/ml in 8 h. Plasma concentrations of SN-38 remained between 2 and 10 ng/ml. Mean values of systemic clearance, mean residence time and distribution volume at steady state, the major pharmacokinetic parameters for CPT-11, were 13.3 (ml/min per kg), 192 (min) and 2553 (ml/kg), respectively. The initial plasma concentration ratio of lactone to total CPT-11, 76%, declined to about 20% within 75 min, and the final ratio was about 40% at 8 h; the initial ratio of SN-38 was 72%, dropped to 34% within 70 min and finally recovered to 55% at 8 h. CONCLUSION: Comparison with human data revealed that systemic clearances of CPT-11 and the maximum AUC of SN-38 were not as different between humans and monkeys as between humans and mice, but the metabolic conversion of CPT-11 into SN-38 in monkeys was significantly lower than in humans.
We report a case of gastrojejunal fistula caused by benign gastric ulcer, a very rare condition. The patient was an 81-year-old-woman who had had multiple recurrences of gastric ulcer. She also had diabetes mellitus. She was admitted to our hospital because of a left femoral head fracture, necessitating a mechanical bone head exchange operation. She had severe abdominal pain and anemia on the 48th postoperative day. Gastroendoscopic examination revealed a giant ulcer with a long-axis diameter of more than 5cm on the lesser curvature of the gastric body. She was treated with intravenous famotidine and all oral intake was restricted; her symptoms were alleviated. Two weeks later, a fistula had formed between the stomach and the jejunum just anal to the duodeno-jejunal flexure. She was placed on an ulcer diet, and was discharged with no symptoms on the 151st postoperative day. She has remained asymptomatic for 1 1/2, years to date. Lack of H2-antagonist administration, operative stress, and administration of ipriflavone appeared to have induced gastric ulcer recurrence, and formation of the fistula between the stomach and the jejunum seemed to have been facilitated by the patient being very lean and having minimal mesenteric adipose tissue.
An extremely unusual case of gastric outlet syndrome, otherwise known as Bouveret's syndrome, caused by a large gallstone impacted in the duodenum due to a cholecystoduodenal fistula (CDF), is described herein. Another large gallstone impacted in the CDF itself was also detected. As endoscopic extraction of the gallstone from the duodenum proved unsuccessful, and a laparotomy was required. Our patient, being 88 years old, is probably the oldest patient recorded in the literature of this syndrome. The methods of establishing a correct diagnosis by endoscopy and recent therapeutic strategies are discussed following the case report.
This paper presents two patients with chronic progressive hearing disturbance. Each patients had an intrameatal tumour, part of which extended to the cerebellopontine (CP) angle. In both cases, the patients were initially diagnosed with an acoustic neurinoma. A 63-year-old male experienced a hearing disturbance in the left ear for 1.5 years prior to visiting our hospital. Magnetic resonance (MR) imaging revealed a mass which was surgically resected. The tumour originated from the intrameatal dura mater. Histologically, the tumour was a meningioma. Similarly, a 53-year-old male presented with systemic lymphoma diagnosed 10 months earlier, and a hearing disturbance in the right ear that began 3 months prior to visiting our hospital. MR imaging prior to chemotherapy revealed a mass which extended to the CP angle. Part of the tumour in the CP angle disappeared after chemotherapy, suggesting a secondary lymphoma. Another tumour appeared later in Meckel's cave on the left side; however, it decreased in size following repeated chemotherapy. The present results indicate that differential diagnosis of intrameatal tumours and acoustic neurinomas may be difficult due to the small tumour size. Recent progress in neuroradiology may allow distinction of intrameatal tumours as a separate tumour classification. Our second patient is the sixth reported case of a CP angle lymphoma in the literature.
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The effects of clonidine, an alpha2 adrenoceptor agonist, on extracellular concentrations of dopamine and gamma-aminobutyric acid (GABA) in the nucleus accumbens of rats were studied by using in vivo brain microdialysis. Clonidine (5 microg/kg i.v.) significantly decreased the brain microdialysate concentration of dopamine in the nucleus accumbens up to a maximum of 16% at its peak effect. This effect was inhibited by a dose of idazoxan (10 microg/kg i.v.), an alpha2-adrenoceptor antagonist. which itself did not affect the efflux of dopamine. A smaller dose of clonidine (1 microg/kg i.v.), which had no significant effect on dopamine efflux per se, decreased the dopamine efflux (21% reduction) when given together with an ineffective dose of midazolam (0.075 mg/kg i.v.), a benzodiazepine receptor agonist. The effect of clonidine (5 microg/kg i.v.) on mesolimbic dopamine efflux was abolished by bicuculline (1 mg/kg i.v.), a GABA(A) receptor antagonist, counteracted by beta-carboline-3-carboxylate ethyl ester (beta-CCE, 3 mg/kg i.p.), a benzodiazepine receptor inverse agonist, but not affected by flumazenil (6 microg/kg i.v.), a benzodiazepine receptor antagonist. Clonidine (5 microg/kg i.v.) increased the dialysate concentration of GABA in the nucleus accumbens up to a maximum of 250% at its peak effect, but not in the ventral tegmental area. It is hypothesized that GABA(A) binding sites in the nucleus accumbens form part of the sequence of events that is triggered by clonidine in an alpha2-adrenergic-specific manner and that ultimately results in a decreased release of dopamine in the nucleus accumbens.
To gain more insight into the understanding of myelodysplastic syndromes (MDS) as they occur in Thailand, a retrospective clinicopathologic analysis was conducted in patients (age > 15 years) diagnosed as MDS from January 1992 to December 1996 at the five major medical centers in various geographic regions of the country. The central reviewers independently examined the bone marrow and peripheral blood smears of all the patients and classify the disease according to the French-British-American (FAB) classification. There were a total of 117 eligible patients. The median age of the patients was 56 years (range 16-86). The male:female ratio was 1:1. Thirty-two percent of the patients were younger than 40 years. The frequency of the FAB subtypes was RA/RARS, 54.7; RAEB, 23.1; CMML, 9.4; and RAEB-T, 12.8%. Anemia was the most common symptom presenting in 84.6% of the patients. In the 34 patients in whom the cytogenetics in the bone marrow were analysed, 44.1% revealed abnormalities. Of these, monosomy 7 and trisomy 8 were the most common aberration, each being detected in 26.7% of the patients. Transfusions were the main therapeutic modality in 80% of the patients. Kaplan-Meier analysis revealed a 5 year survival rate of 29% for the whole group with a median survival of 24 months. Twenty-five percent of the patients had progressed to acute myelogenous leukemia (AML) with a median time to disease-progression of 23 months. The median survival for RA/RARS, RAEB, CMML and RAEB-T were 58.4, 19.9, 10.7 and 8.7 months, respectively (P < 0.001). The stepwise Cox regression analysis revealed the percentage of blasts in the bone marrow as the only parameter significantly associated with survival and disease progression. On comparison with data from other countries, the age of Thai patients with MDS is considerably lower than the western population but is comparable to other asian countries. The distribution of the FAB subtypes and the survival of the patients are similar. The major prognostic features, however, lie in the percentage of blasts in the bone marrow rather than the degree of the observed cytopenia.
We retrospectively reviewed clinical and hematologic features of nine patients with acquired idiopathic sideroblastic anemia (AISA). Seven of them had ringed sideroblasts (RS) more than 15% of marrow nucleated cells. RS persisted in the marrow even in the remaining two patients who had a relatively low marrow erythroblasts despite RS ranging from 1/4 to half of the marrow erythroid series. However, RS declined in proportion in another two patients of the nine whose disease progressed to refractory anemia with excess of blasts (RAEB), although a high proportion of RS reappeared in one patient at the time of relapse following allogeneic marrow transplantation. A similar decline of RS concomitant with disease progression was also seen in seven additional patients with RAEB or RAEB in transformation (RAEB-t) with sideroblastic erythropoiesis. Cytogenetic abnormalities, although rare initially, became detectable either at the time of disease progression or at the worsening of anemia in AISA. These observations suggest that the majority of AISA fall in the category of myelodysplasia, and that a progressive decline in RS is part of the natural history of myelodysplasia. Closer follow-up of the proportion of RS in patients with AISA is warranted to better understand its biologic significance.
Adherent bacterial cells on the surfaces of two dental porcelain ceramics, three composite resins and human enamel were examined using four types of bacteria strains. Their adherent cells were counted on saliva-coated and uncoated material surfaces after sonication, and contact angle and zeta potential were measured for each adherent cell tested. A correlation between contact angle and bacterial cells on an uncoated surface was found to be higher in two Streptococcus sanguis cells than in S. mutans Ingbritt and S. sobrinus OMZ 176, whereas there appeared to be a higher correlation between S. mutans Ingbritt or S. sobrinus OMZ 176 and zeta potential on the uncoated surface. On the saliva-coated surface, a significantly high correlation was found between the adherent cells, with the exception of S. sanguis ATCC 10 557, and the zeta potential. Contact angle and zeta potential values were small when the surfaces of the materials were coated with saliva, as compared with those on the uncoated surface. The sonication condition (120 s) of adherent cells on the surface of the material significantly depended on the types of bacteria cells, showing that S. mutans Ingbritt (>50-60%) had a greater removal percentage than the others (<50%).
Using a polymerase chain reaction-mediated cloning procedure, we have identified a novel member, termed ANA (from Abundant in Neuroepithelium Area), of Tob/BTG1 family of antiproliferative genes. Molecular cloning and analysis of cDNAs revealed that the human and mouse ANA encoded a protein of 252 amino acids. The amino-terminal half of ANA was homologous to the previously characterized antiproliferative gene products, BTG1, PC3/TIS21/BTG2, and Tob. The human ANA gene was localized at chromosome 21q11.2-q21.1. ANA was expressed in a variety of tissues and cell lines, its expression being high in the ovary, testis, prostate, thymus, and lung. Further analysis revealed that ANA expression was high in the ventricular zone of the developing central nervous system. Finally, overexpression of ANA impaired serum-induced cell cycle progression from the G0/G1 to S phase. In conclusion, ANA is a fourth member of the Tob/BTG1 family that might play roles in neurogenesis in the central nervous system.
Data on endogenous thrombopoietin (TPO) levels and their regulation in myelodysplastic syndromes (MDS) are sparse. We examined the plasma TPO level of 85 MDS patients by a sensitive enzyme immunoassay and the platelet expression of TPO receptor (TPO-R) protein, which metabolizes endogenous TPO, in 19 MDS patients with an equilibrium binding assay using 125I-TPO. The MDS patients had higher plasma TPO levels (7.0 +/- 9.3 fmol/ml) than 52 normal subjects (P < 0.0001). Refractory anaemia (RA) patients (n = 39) had higher plasma TPO levels than patients (n = 28) with RA with excess blasts (RAEB) or RAEB in transformation (RAEB-t) (P = 0.0002), irrespective of similar platelet counts in these groups. The plasma TPO level correlated inversely with the platelet count in RA patients (P = 0.0027) but not in RAEB and RAEB-t patients (P = 0.7865). These data suggest that the physiological pathway for TPO production and metabolism is conserved, at least partially, in RA, but deranged in RAEB/RAEB-t. The number of TPO-R per platelet was significantly smaller in 19 MDS patients (17.5 +/- 13.3) than in normals (P = 0.0014), but similar between RA patients and patients with RAEB and RAEB-t. Further, the bone marrow megakaryocyte count, determined in 31 MDS patients, was quite similar between RA patients and patients with RAEB or RAEB-t. Thus, in addition to thrombocytopenia, a reduced platelet TPO-R number may contribute to elevated plasma TPO levels in MDS, and a regulatory pathway for circulating TPO other than platelet TPO-R and marrow megakaryocytes, such as blasts expressing TPO-R, may operate in RAEB/RAEB-t.
A particular T cell population expressing NK cell markers, CD56 and CD57, exists in humans. Many CD56+ T and CD57+ T cells (i.e. NK T cells) exist in the liver and increase in number in the blood with ageing. They may be a human counterpart of extrathymic T cells, similar to NK1.1+ CD3int cells seen in mice. We investigate here the existence of such NK T cells in human cord blood and the in vitro expansion of these cells by the stimulation of human recombinant IL-2 (rIL-2). There were very small populations (< 1.0%) of CD56+ T cells, CD57+ T cells, and gamma delta T cells in cord blood. However, all of these populations increased in number after birth and with ageing. When lymphocytes in cord blood were cultured with rIL-2 (100 U/ml) for 14 days, CD56+ T cells expanded up to 25% of T cells. CD57+ T cells were never expanded by these in vitro cultures. The expansion of gamma delta T cells (mainly V gamma9- nonadult type) also occurred in the in vitro culture. A considerable proportion of CD56+ T cells was found to use V alpha24 (i.e. equivalent to invariant V alpha14 chain used by murine NK T cells) for TCR alpha beta. These results suggest that neonatal blood contains only a few NK T cells but CD56+ NK T cells and gamma delta T cells are able to expand in vitro.
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Conventional T cells (i.e. TCRhigh) are generated by the main stream of T-cell differentiation in the thymus. However, primordial T cells (i.e. TCRint) are generated by extrathymic pathways and an alternative intrathymic pathway. Since TCRint cells contain self-reactive clones, the diversity of the T-cell antigen receptor (TCR) complementarity-determining region (CDR) 3 was examined. The predominant Vbeta8.2+ clones among TCRint cells were selected for DNA sequencing. Thymectomized, irradiated mice subjected to bone-marrow transplantation (BMT) were used; graft-versus-host disease (GVHD), B6-->(B6xC3H/He)F1 and syngeneic BMT, B6-->B6. In these combinations, only TCRint cells were generated. Vbeta8.2+ cells with a low diversity of CDR3 of V-gene expanded in GVHD mice. Vbeta8.2+ cells of TCRint and TCRhigh cells in normal mice were polyclonal, showing that the former has a lower diversity of CDR3 than the latter. The clonality of activated TCRhigh cells was examined, in which CD3high cells (bml2 mice) were injected into 1 Gy-irradiated B6 nude mice. Some Vbeta8.2+ clones among TCRhigh cells were expanding but the diversity of CDR3 was greater than that of CD3int cells, despite the fact that the recognition site of the H-2 difference was smaller. Taken together with invariant usage of V alpha14, these results suggest that TCRint cells have a low diversity of CDR3 of Vbeta genes.
The ability of skin to maintain its protective structural and functional integrity depends on both resident and circulating cells. Until now, it was thought that dendritic antigen presenting cells of epidermis (Langerhans cells) were replaced by circulating bone marrow derived precursors. Here we show by immunostaining studies of timed biopsies taken from human skin after ultraviolet exposure, that hair follicle is a critical reservoir of Langerhans cells that repopulate epidermis depleted of Langerhans cells by a single four minimal erythema dose of ultraviolet B. Immunostaining with antibodies to thymidine dimers showed that ultraviolet B only penetrated the superficial hair follicle opening, whereas deeper follicle was relatively protected. Langerhans cells migrating from hair follicle into epidermis 72 h after ultraviolet exposure have a partial deficiency of molecules important to T cell costimulation. We used four color flow cytometry to show that Langerhans cells isolated from epidermis 72 h after ultraviolet B can upregulate CD40 but not B7-1 or B7-2 expression in culture, suggesting a different phenotype of hair follicle Langerhans cells. Therefore, the hair follicle is a specialized immune compartment of the skin that serves as an intermediate reservoir of Langerhans cells between bone marrow and epidermis, and that may play a critical role in immune surveillance.
Interferon-gamma (IFN-gamma) produced by lesional T cell clones is critical for the induction into G1 of the cell cycle by psoriatic keratinocyte stem cells; however, direct data demonstrating psoriatic lesional T cell subset IFN-gamma expression, and quantitation at a single cell level to calculate in vivo proportions, are lacking. In this study, using flow cytometry of freshly isolated normal and psoriatic lesional T cells from keratome biopsies, we found elevated CD3+, CD4+, and CD8+ T cells in all compartments of psoriatic skin, compared with normals. Using Brefeldin A to induce short-term intracellular accumulation of IFN-gamma in T cells capable of IFN-gamma production, we found that 90% of psoriatic patients have IFN-gamma-producing T cells at a greater proportion of their CD3+ cells than normals, with a mean of 16%+/-3%, as compared with 4%+/-2% in normal epidermis (p = 0.01). Expressed as density in the tissue, the IFN-gamma+ CD3+ cell number in psoriatic epidermis was 97+/-22 per mm2 surface area, as compared with 4.4+/-1.8 per mm2 of normal epidermis (p = 0.002). Thus, the total number of IFN-gamma+CD3+ T cells in the skin of a patient with 20% involvement is estimated to be 3.9 x 10(8). CD4+ and CD8+ IFN-gamma+ T cells were both elevated in psoriatic epidermis (p = 0.04 and p = 0.008, respectively) relative to normal skin. In the dermis, only 44% of patients demonstrated a higher percentage of IFN-gamma-producing T cells than did normals (p = 0.1), possibly indicating dilution, in some patients, by fresh infiltrating T cells. Interleukin-4 was not found by a combination of flow cytometry, reverse transcriptase-polymerase chain reaction, western blot, and immunoprecipitation. In conclusion, a significant portion of lesional T cells in psoriasis are IFN-gamma producing, without interleukin-4. The increased numbers of both IFN-gamma+CD4+ and IFN-gamma+CD8+ T cells indicate that both CD4+ and CD8+ IFN-gamma+ T cells are present in appropriate anatomic locations to sustain the lesional pathology.