[Evolution of treatments for prostatic cancer].
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Humans↗
Biomedical subjects
Y Aso
Publications and source records attributed to Y Aso.
Oligo(dT)-immobilized pipette tip: efficient new methodology for mRNA preparation and direct gene amplification.
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Globins↗
RNA chip: quality assessment of RNA by microchannel linear gel electrophoresis in injection-molded plastic chips.
Two major components of rRNA (18S and 28S rRNA) were separated by electrophoresis in injection-molded acrylic chips with a microchannel 100 microm in width, 40 microm in depth, and with 1 cm of separation distance. Microchannels were filled with 4 g/L hydroxypropylmethylcellulose as sieving polymer and 5 mg/L ethidium bromide for RNA staining. The fluorescent signals were detected by a fluorescent microscope equipped with a photometer and 590 nm emission filter. The assay is rapid (<3 min), reproducible, RNase-free, and requires only 1-2 microL of sample. The detection limit was approximately 10 mg/L (10 ng/microL), 100-fold lower than that for conventional agarose gel electrophoresis. Because only 0.1 nL of the loaded sample was used for electrophoresis, the detectable peaks of rRNA in the separation were derived from less RNA than in a single cell. Because the quality of RNA is critical for RNA-related diagnostic tests, disposable plastic chips will be useful for quality assessment of RNA.
Animals↗
Direct reverse transcription-PCR on oligo(dT)-immobilized polypropylene microplates after capturing total mRNA from crude cell lysates.
To simplify gene expression analysis, oligo(dT)-immobilized polypropylene microplates were used serially to capture mRNA, synthesize cDNA, and amplify specific genes. The amounts of immobilized oligonucleotide, hybridized mRNA, and synthesized cDNA were quantified fluorometrically using either Yoyo-1 or AttoPhos. The immobilized oligonucleotides captured approximately 40-55% of mRNA directly from crude cell lysates. Hybridized mRNA was then amplified by one-step reverse transcription (RT)-PCR with rTth polymerase or two-step PCR with initial cDNA synthesis followed by PCR, where the latter exhibited more sensitivity. In two-step RT-PCR, microplates can be reused for multiple PCRs with the same or different primer sets because synthesized cDNA was covalently attached to the plates at its 5' end. We believe this microplate may be acceptable as a platform for various mRNA expression analyses, including basic research, drug screening, and molecular toxicology, as well as for molecular pathological diagnostics.
Animals↗
A rare case of a thyrotropin-secreting pituitary tumor which responded to methimazole.
A 52-year-old Japanese male complained of palpitations and excessive sweating. He showed evidence of hyperthyroidism, but without suppression of the serum thyroid-stimulating hormone (TSH). On admission, the serum level of the alpha-subunit of TSH was elevated, but tests for thyroid autoantibodies were negative. The TSH response to thyrotropin-releasing hormone (TRH) was blunted. Imaging studies revealed a pituitary tumor 2 cm in diameter. Administration of methimazole lowered the serum levels of thyroid hormones, and elevated the serum level of TSH. These findings led to the diagnosis of a thyrotropin-secreting pituitary tumor. Immunohistochemical analysis and electron microscopic findings verified the diagnosis.
Antithyroid Agents↗
Assessment of hormone refractory prostate cancer.
OBJECTIVES: To define guidelines for the assessment of treatment in patients with hormone-refractory prostate cancer (HRPC). METHODS: In the light of modern research, and taking new treatment options into account, the Committee essays to specify different categories of patients entering clinical trials, and to define response criteria and those endpoints that are relevant in phase III studies and in short-term follow-up. RESULTS: HRPC comprises a range of disease states with varying responsiveness to therapy and length of survival. Patients with progression as evaluated by increasing prostate-specific antigen (PSA) values alone have a more favorable prognosis than those presenting with increasing tumor spread. In the assessment of these patients, the modes of previous therapy and the kind of tumor progression must be taken into account. The benefit of treatment of HRPC is often modest. While duration of survival remains the main and ultimate endpoint, the means of measuring short-term responsiveness to therapy are limited. A minority of patients have measurable tumor lesions. Decrease of PSA or other biochemical tumor markers may indicate depression of the tumor activity, but is not always associated with prolongation of survival. A variety of new treatments in HRPC are being investigated. They affect measurable tumor parameters in different ways. CONCLUSIONS: When a new agent is to be tested, it is important to measure all possible parameters before deciding which particular ones are appropriate for future investigations of this agent. In symptomatic patients, evaluation of subjective parameters, for example, relief of pain or improvement of performance status, is often the most reliable measure of treatment effect. However, these parameters should be clearly defined.
Antineoplastic Agents, Hormonal↗
Alterations in serum levels of 1 alpha,25(OH)2 D3 and osteocalcin in patients with early diabetic nephropathy.
UNLABELLED: Serum levels of markers for bone remodeling and diabetic metabolic markers were measured in subjects with non-insulin-dependent diabetes mellitus (NIDDM) to investigate the relationship between early diabetic nephropathy and calcium/bone metabolism. 1 alpha,25(OH)2 D3 (Vit D), osteocalcin (OC), intact parathyroid hormone (PTH) and urine albumin excretion (UAE) were measured in all subjects. Serum levels of Vit D and OC were significantly decreased in diabetic subjects compared to age-matched, non-diabetic controls. In diabetic patients, a significant positive correlation was observed between intact PTH and OC. No significant correlation was found between levels of Vit D and OC. In early diabetic nephropathy without increased serum creatinine, Vit D decreased and OC increased with increasing UAE. Levels of hemoglobin Alc (HbAlc) and fructosamine (FRA) were not correlated with levels of Vit D or OC. Levels of Vit D were decreased and levels of OC were increased in diabetic subjects with proliferative retinopathy or with micro- or macro-albuminuria. CONCLUSIONS: Results of the present study indicate that changes in bone remodeling markers such as Vit D and OC levels are present in the early stages of diabetic nephropathy, and that circulating intact PTH is important in restoring the reduced OC levels in diabetic patients, probably as a reflection of bone remodeling.
Albuminuria↗
Evaluation of microangiopathy of the skin in patients with non-insulin-dependent diabetes mellitus by laser Doppler flowmetry; microvasodilatory responses to beraprost sodium.
To determine the relationship of skin microangiopathy and other diabetic microvascular complications, we measured changes in skin blood flow after the administration of the prostacyclin (PGI2) analogue, beraprost sodium (BPS), in 82 patients with non-insulin-dependent diabetes mellitus and 20 healthy subjects. The diabetic patients had various degrees of retinopathy and nephropathy. Using laser Doppler flowmetry we measured skin blood flow at the dorsum of the right big toe at various times after the administration of 40 micrograms BPS and calculated the blood flow change (delta flux = peak flux--basal flux). We also determined the ankle pressure index (API), an ankle/brachial systolic pressure ratio. The basal blood flow was higher in healthy subjects than in diabetic patients (P < 0.001). BPS significantly increased blood flow in both diabetic patients and healthy subjects (P < 0.001). In all 102 subjects delta flux was positively correlated with the API (R = 0.40, P < 0.001). Despite no differences in API among the diabetic retinopathy and nephropathy subgroups, the delta flux in diabetic patients with progressive retinopathy and macroalbuminuria was significantly lower than in healthy subjects or in diabetic patients with less severe retinopathy and nephropathy (P < 0.05). The results suggested that BPS increases skin blood flow and the flow increase induced by BPS is related partly to the levels of API. The effect of BPS on skin blood flow decreased with an increases in the severity of retinopathy and nephropathy. Diabetic skin microangiopathy appears to coexist with other microvascular diabetic complications and may be proportional to their severity.
Adult↗
Softening temperature of lyophilized bovine serum albumin and gamma-globulin as measured by spin-spin relaxation time of protein protons.
We investigated the usefulness of the spin-spin relaxation time (T2) of protein protons as a probe for evaluating the molecular flexibility of freeze-dried protein formulations. It is proposed that the microscopic softening temperature determined from changes in the T2 of protein protons (Ts(T2)) is an important characteristic of freeze-dried protein formulations, the glass transition temperature (Tg) of which is generally difficult to determine by differential scanning calorimetry. We determined the molecular flexibility of lyophilized bovine serum albumin (BSA) and bovine gamma-globulin (BGG) by measuring the T2 of protein and water protons as well as the spin-lattice relaxation time (T1) of the latter as a function of temperature. The flexibility of freeze-dried BSA and BGG cakes markedly varied at temperatures above and below the Ts(T2), affecting the stability of the proteins. The denaturation and subsequent aggregation of lyophilized BSA and BGG cakes with a relatively high water content was enhanced in the softened state at temperatures above the Ts(T2). Lyophilized cakes with an extremely low water content were significantly denatured, even in the unsoftened state at temperatures below the Ts(T2), probably due to the thermodynamically unstable structures of protein molecules generated by a loss of structural water.
Chromatography, Gel↗
Dependence of the molecular mobility and protein stability of freeze-dried gamma-globulin formulations on the molecular weight of dextran.
PURPOSE: The effect of the molecular weight of dextran on the molecular mobility and protein stability of freeze-dried serum gamma-globulin (BGG) formulations was studied. The stabilizing effect of higher molecular weight dextran is discussed in relation to the molecular mobility of the formulations. METHODS: The molecular mobility of freeze-dried BGG formulations containing dextrans of various molecular weights was determined based on the free induction decay of dextran and water protons measured by proton NMR. The protein stability of the formulations was determined at temperatures ranging from 20 to 70 degrees C by size exclusion chromatography. RESULTS: Changes in the molecular mobility of freeze-dried formulations that occurred at temperatures below the glass transition temperature could be detected as the molecular mobility-changing temperature (Tmc), at which dextran protons started to exhibit a Lorentzian relaxation decay due to higher mobility in addition to a Gaussian relaxation decay. Tmc increased as the molecular weight of dextran increased. The proportion of dextran protons which exhibited the higher mobility relaxation process (Phm) at temperatures above Tmc decreased as the molecular weight of dextran increased. Protein stability was closely related to molecular mobility. The temperature dependence of the denaturation rate changed at around Tmc, and denaturation in the microscopically liquidized state decreased as Phm decreased with increasing molecular weight of dextran. CONCLUSIONS: The effect of the molecular weight of dextran on the protein stability of freeze-dried BGG formulations could be explained in terms of the parameters obtained by 1H-NMR such as Tmc and Phm. These parameters appear to be useful in preformulation and stability prediction of freeze-dried formulations.
Calorimetry, Differential Scanning↗
Predictive value of serum immunosuppressive acidic protein for staging renal cell carcinoma: comparison with other tumour markers.
OBJECTIVE: To examine the usefulness of serum immuno-suppressive acidic protein (IAP) as a predictor for staging renal cell carcinoma (RCC), using receiver-operator characteristic (ROC) analysis, and to compare IAP with other tumour markers. PATIENTS AND METHODS: From September 1983 to December 1995, serum IAP was measured in 133 untreated patients with RCC (mean age 60.1 years, SD 11.4. range 31-84). The erythrocyte sedimentation rate (ESR), the levels of fibrinogen, C-reactive protein (CRP), and alpha 2-globulin were also measured. To compare these markers as predictors of local involvement of the renal capsule, lymph node and distant metastasis, the area under the corresponding ROC curve was calculated. Tumour size at the time of resection was added in this analysis for comparison with the levels of these tumour markers. RESULTS: The final pathological stage was T1 or T2 in 101 patients and T3 or T4 in 32, while it was N0 in 122 patients, N1-3 in seven, M0 in 114 patients and M1 in 19. The area of the ROC curve for tumour size was greatest (0.843) for staging of the local extent (T1/T2 versus T3/T4) and that for IAP was 0.714, similar to the values for fibrinogen, ESR and CRP. For predicting lymph node metastasis, IAP and fibrinogen were the most important (0.864). However, IAP alone (0.894) was the most important predictor of distant metastasis. Using an IAP threshold of 600 micrograms/mL gave a high sensitivity and specificity for detecting lymph node and distant metastasis. CONCLUSION: IAP is a valuable predictor of lymph node and distant metastasis in patients with RCC, although it is inferior to tumour size in predicting local involvement of the renal capsule. The appropriate threshold value of IAP for detecting lymph node and distant metastasis is 600 micrograms/mL.
Adult↗
Clinical characteristics of patients with the initial diagnosis of NIDDM with positivity for antibodies to glutamic acid decarboxylase.
UNLABELLED: The measurement of islet cell antibodies (ICA) and antibodies to glutamic acid decarboxylase (GAD-Ab) is clinically useful in evaluating patients with insulin-dependent diabetes mellitus (IDDM). Our objective was to correlate the clinical characteristics of patients with non-insulin-dependent diabetes mellitus (NIDDM) who exhibited positivity for GAD-Ab vs. patients who were negative for this enzyme. The serum level of GAD-Ab was measured by radiobinding assay (RBA) using pig brain GAD. The prevalence of GAD-Ab in the 181 patients was low; the 8 involved subjects (4.4%) were all females. The NIDDM patients who were GAD-Ab-positive were significantly younger, experienced diabetes onset at an early age, had a shorter duration of diabetes, a shorter interval between diabetes onset to initiation of insulin therapy, a lower body mass index (BMI), a lower serum C-peptide value, and required a higher dose of insulin. A higher proportion of the GAD-Ab-positive patients was receiving insulin therapy. CONCLUSIONS: Clinical characteristics of patients with NIDDM who were positive for GAD-Ab differed significantly from those of the patients negative for GAD-Ab. The profile of the GAD-Ab-positive patients with NIDDM resembled that of those with IDDM.
Adult↗
Epidemiologic survey of lower urinary tract symptoms in Asia and Australia using the international prostate symptom score.
BACKGROUND: The prevalence of lower urinary tract symptoms was determined by survey as an initial step in estimating the significance of benign prostatic hyperplasia (BPH) in Asia and Australia. METHODS: The symptom index (0 to 35) and quality-of-life (QOL) index (0 to 6) of the international prostate symptom score were measured in 7588 men in 9 Asian countries and 146 men in Australia. RESULTS: The percentages of Asian men considered to be symptomatic (symptom index > or = 8) were 18%, 29%, 40%, and 56% in the age groups of 40 to 49, 50 to 59, 60 to 69, and 70 to 79 years, respectively. For Australian men, these figures were 36%, 33%, and 37% in the 50 to 59, 60 to 69, and 70 to 79 year age groups, respectively. CONCLUSIONS: Our estimates indicate that the prevalences of symptomatic men in Asia and Australia are similar to or greater than those in Europe and America, and suggest BPH is similarly common in these areas.
Adult↗
Preoperative endocrine therapy for clinical stage A2, B, and C prostate cancer: an interim report on short-term effects. Prostate Cancer Study Group.
BACKGROUND: Preoperative endocrine therapy has been suggested to improve surgical radicality and/or patient prognosis in prostate cancer. METHODS: Patients with clinical stage A2, B, and C prostate cancer were randomized to either group I (n = 113) or group II (n = 111). Group I patients were to receive preoperative endocrine therapy consisting of leuprolide and chlormadinone for 3 months, followed by radical prostatectomy with lymph node dissection. Group II patients were to undergo the surgery before endocrine therapy. RESULTS: Group I patients showed a remarkable decrease in prostate-specific antigen (PSA) (mean +/- SE: 41.8 +/- 8.6 ng/mL to 2.7 +/- 0.7 ng/mL) and prostate volume (29.8 +/- 1.7 mL to 21.2 +/- 1.6 mL) during the preoperative therapy. Histopathologic analysis showed a significant difference in the rates of down-staging (19.1% in group I versus 3.3% in group II), positive surgical margins (63.8% versus 81.3%) and positive lymph node metastasis (20.7% versus 36.5%). No significant difference was detected in operating features. Subgroup analyses indicated that beneficial effects were correlated positively with degree of histologic differentiation and negatively with the basal PSA level. CONCLUSIONS: Preoperative endocrine therapy reduced local extension of prostate cancer, and the effects depended on histologic differentiation and PSA level. Long-term follow-up data are needed to determine the effects on the patient prognosis.
Aged↗
Further studies on thermal denaturation of pyruvate dehydrogenase complex from Bacillus stearothermophilus.
Thermally induced changes in pyruvate dehydrogenase complex (PDC) from B. stearothermophilus were examined mainly at temperatures from 60 degrees to 70 degrees C. Accompanied by inactivation of pyruvate decarboxylase, light scattering decreased, and ANS fluorescence increased. These changes including the inactivation were approximately first-order reactions, and the values of rate constants were greatly dependent on temperature. Chromatographic studies showed that any polypeptides were in associated forms and that final products were aggregates (> 230S) and an assembly (48S) smaller than PDC. The aggregates and assembly were rich in decarboxylase and lipoate acetyltransferase, respectively. It was suggested that, during the thermal denaturation, a decarboxylase was dissociated from PDC and immediately involved in aggregates.
Chromatography, Gel↗
Purification and characterization of two chitinase isoforms from the bulbs of gladiolus (Gladiolus gandavensis).
Two chitinase isoforms, designated GBC-a and GBC-b, were purified from the bulbs of gladiolus (Gladiolus gandavensis) using CM-cellulose column chromatography followed by Butyl-Toyopearl 650 M hydrophobic column chromatography, gel filtration on Sephadex G-75, and Mono-S FPLC. GBC-a and GBC-b are weakly acidic and weakly basic proteins with molecular masses of 30 kDa, and isoelectric points of 6.0 and 7.5, respectively. GBC-a and GBC-b were found to be homologous proteins with similar amino acid compositions and N-terminal sequences. The number of half-cystine residues in GBC-a and GBC-b was only one each, which is much lower than those of plant class I (15-17 Cys residues/mol), class II (5-8 Cys residues/mol), and class III (6 Cys residues/mol) chitinases. The N-terminal sequences of GBC-a and GBC-b were completely different from those of plant three classes of chitinases. The optimal pHs of these chitinases toward glycolchitin were pH 5. GBC-a hydrolyzed (GlcNAc)5 into (GlcNAc)2, (GlcNAc)3 and (GlcNAc)4, and (GlcNAc)5 into (GlcNAc)2 and (GlcNAc)3.
Amino Acid Sequence↗
Stiff-man syndrome associated with antecedent myasthenia gravis and organ-specific autoimmunopathy.
We describe a case of stiff-man syndrome accompanied by diabetes mellitus, Hashimoto's thyroiditis and the antecedent myasthenia gravis. The diagnosis of stiff-man syndrome was made based on not only clinical findings and the characteristic electromyographic pattern but also the presence of antibodies to glutamic acid decarboxylase in the serum and cerebrospinal fluid. Stiff-man syndrome is known to be associated with organ-specific autoimmunopathy including insulin-dependent diabetes mellitus. The present case is the first one that stiff-man syndrome was preceded by myasthenia gravis of organ-specific autoimmunopathy. Stiff-man syndrome in the present case probably represents the one of fully expressed manifestations from the broad spectrum of organ-specific autoimmunopathy caused by the loss of self-tolerance.
Adult↗
Evaluation of skin vasomotor reflexes in response to deep inspiration in diabetic patients by laser Doppler flowmetry. A new approach to the diagnosis of diabetic peripheral autonomic neuropathy.
OBJECTIVE: To evaluate the peripheral sympathetic function in feet of NIDDM patients by means of laser Doppler flowmetry. RESEARCH DESIGN AND METHODS: After deep inspiration, we measured the vasoconstrictor response in the feet of 51 patients with NIDDM, as compared with those of 20 healthy control subjects, using laser Doppler flowmetry. Subjects whose skin temperature was < 32 degrees C were excluded from our study because a skin temperature of approximately 34 degrees C is the optimal temperature for the evaluation of skin vasomotor reflexes in response to a deep inspiration by laser Doppler flowmetry. RESULTS: The vasoconstrictor response to deep inspiration in the big toe was significantly decreased in NIDDM patients compared with healthy subjects (26.8 +/- 2.0 vs. 48.3 +/- 18.5%, P < 0.0001). In NIDDM patients, the vasoconstrictor response was positively correlated with the duration of diabetes, the median motor and sensory nerve conduction velocities, the coefficient of variation of the R-R interval at rest, and the postural fall in systolic blood pressure. The vasoconstriction was inversely correlated with the vibratory perception threshold. CONCLUSIONS: Vasomotor reflexes in the lower limbs were markedly impaired in NIDDM patients. The measurement of vasoconstrictor responses to deep inspiration by using laser Doppler flowmetry is a novel and useful method for detecting peripheral sympathetic failure in diabetic patients.
Blood Flow Velocity↗