Short course regimens; 2HRZ (E)(S)/4HR (E), 6HRS (E)/3-6HR and 6-9HR have been accepted as a standard chemotherapy (SC) for initial treatment of pulmonary tuberculosis in Japan. We studied the frequency of the treatment completion, the causes of the treatment failure and the outcome of the patients in whom INH or RFP was discontinued within 6 months after starting SC. The subjects included 597 newly diagnosed culture positive pulmonary tuberculosis patients admitted to 16 national hospital in 1996. Results were as follows. 1. In 47 (7.9%) of the 597 patients, either INH (19; 3.2%) or RFP (33; 5.5%) was discontinued. These 47 cases were defined as a SC incompleted group and the other 550 as a SC completed group. 2. The patients in the SC incompleted group were seen more frequently in the ages of 20s (11.9%), 50s (10.9%), 60s (11.7%) or 70s (11.4%). 21 (13.6%) of 154 female patients and 26 (5.9%) of 443 male patients were in the SC incompleted group. 3. The causes of cessation of INH or RFP were drug side effects (33; 5.5%), drug resistance (10; 1.7%) and complications or underlying diseases (8; 1.3%). 4. Fever or eruption (19; 3.2%) and drug induced hepatitis (12; 2.0%) were frequently seen as drug related side effects causing the cessation of INH or RFP. 5. The rate of culture negative conversion of TB bacilli at 6 months after the start of the treatment was 98.9% in the SC completed and 88.9% in the SC incompleted group respectively. In the SC incompleted group, there were three cases continuously positive and two other patients who relapsed and became culture positive again. In these five patients, INH or RFP was discontinued because of drug resistance.

Adolescent↗

PubMed2001

Medroxyprogesterone acetate therapy for patients with adenocarcinoma of the endometrium who wish to preserve the uterus-usefulness and limitations.

BACKGROUND: To determine the effectiveness of medroxyprogesterone acetate therapy for women with endometrial adenocarcinoma who wish to preserve their uterus. STUDY DESIGN: Fifteen patients with endometrial carcinoma (12 with grade 1 endometrioid adenocarcinoma. 2 with grade 2 adenocarcinoma and 1 with adenoacanthoma) were treated with high-dose medroxyprogesterone acetate alone as primary therapy and their clinical responses evaluated. RESULTS: Seven of the 12 cases (58%) with grade I adenocarcinoma and one of the two (50%) with grade 2 carcinoma responded initially to medroxyprogesterone acetate. The median length of treatment required for regression was 29 weeks. Three patients who initially responded relapsed. Thirteen patients are alive without evidence of disease as of December 1999 (10 to 146 months, median; 4 years and 11 months) and one is continuing medroxyprogesterone acetate therapy as a final follow-up. One patient was lost to follow-up. Two patients have conceived having three healthy infants. CONCLUSION: Treatment of endometrial carcinoma with high-dose medroxyprogesterone acetate could be an alternative to hysterectomy, although the successful rate is limited.

Adenocarcinoma↗

PubMed2000

The correlation between spontaneous and radiation-induced apoptosis in T3B bladder cancer (histological grade G3), and the precedence between the two kinds of apoptosis for predicting clinical prognosis.

PURPOSE: The correlation between the frequency of spontaneous and radiation-induced apoptosis, and the precedence between those for predicting prognosis were studied at clinical level. METHODS AND MATERIALS: Twenty-one patients (mean age, 65.8 years; 16 men and 5 women) with bladder cancer (transitional cell carcinoma Grade 3, T3bN0M0, Stage IIIb) underwent intraoperative radiotherapy: single 30-Gy 12-MV electron beam irradiation to bladder, followed by total cystectomy 6 h after irradiation. The specimens of pretreatment and irradiated bladder cancer were assayed for apoptosis, using TUNEL staining with counter staining of hematoxylin. The apoptotic index (AI) was calculated by dividing the number of apoptotic cells by the total number of cells and multiplying by 100. The Pearson's linear fitting was used to test the correlation between spontaneous and radiation-induced apoptosis. The Kaplan-Meier product-limit estimation was used for overall survival (OS) and freedom from recurrence (FFR). The precedence between spontaneous and radiation-induced apoptosis for predicting the clinical prognosis was estimated using the proportional hazard regression. RESULTS: The mean AI of spontaneous and radiation-induced apoptosis was 1.18 +/- 0.16 and 2.63 +/- 0.45, respectively, which was significantly different. There was strong correlation between spontaneous and radiation-induced apoptosis (r(2) = 0.864, adjusted r(2) = 0.857). Radiation-induced apoptosis was estimated by equation: y (radiation-induced apoptosis) = 2.67 x (spontaneous apoptosis) -0.52. However, the proportional hazard regression test indicated that only spontaneous apoptosis was significant for predicting OS and FFR (&z.sfnc;t&z.sfnc; > 0.2), but radiation-induced apoptosis was not. CONCLUSION: Estimating AI in radiation-induced apoptosis from AI in spontaneous apoptosis is possible. However, spontaneous apoptosis is more accurate in predicting clinical prognosis.

Aged↗

PubMed2000

Promoter analysis of the mouse sterol regulatory element-binding protein-1c gene.

Recent data suggest that sterol regulatory-binding protein (SREBP)-1c plays a key role in the transcriptional regulation of different lipogenic genes mediating lipid synthesis as a key regulator of fuel metabolism. SREBP-1c regulates its downstream genes by changing its own mRNA level, which led us to sequence and analyze the promoter region of the mouse SREBP-1c gene. A cluster of putative binding sites of several transcription factors composed of an NF-Y site, an E-box, a sterol-regulatory element 3, and an Sp1 site were located at -90 base pairs of the SREBP-1c promoter. Luciferase reporter gene assays indicated that this SRE complex is essential to the basal promoter activity and confers responsiveness to activation by nuclear SREBPs. Deletion and mutation analyses suggest that the NF-Y site and SRE3 in the SRE complex are responsible for SREBP activation, although the other sites were also involved in the basal activity. Gel mobility shift assays demonstrate that SREBP-1 binds to the SRE3. Taken together, these findings implicate a positive loop production of SREBP-1c through the SRE complex, possibly leading to the overshoot in induction of SREBP-1c and its downstream genes seen in the livers of refed mice. Furthermore, reporter assays using larger upstream fragments indicated another region that was inducible by addition of sterols. The presence of the SRE complex and a sterol-inducible region in the same promoter suggests a novel regulatory link between cholesterol and fatty acid synthesis.

Animals↗

PubMed2000

Z-335, a new thromboxane A(2) receptor antagonist, prevents arterial thrombosis induced by ferric chloride in rats.

We examined the antithrombotic effect of Z-335 ((+/-)-sodium [2-(4-chlorophenylsulfonylaminomethyl)indan-5-yl]acetate monohydrate), an orally active thromboxane A(2) receptor (TP-receptor) antagonist that ameliorates experimental gangrene, using a rat arterial thrombosis model. The thrombi were induced by topical application of 50% ferric chloride solution to the rats abdominal artery. Z-335 (0.3-3 mg/kg, p.o.) inhibited thrombus formation in a dose-dependent manner. The antithrombotic effect of Z-335 (1 and 3 mg/kg, p.o.) was almost equivalent with that of cilostazol (100 mg/kg, p.o.), a selective phosphodiesterase type III inhibitor. The effect of Z-335 (3 mg/kg, p.o.), but not cilostazol, persisted for 16 h. Z-335, but not cilostazol, inhibited platelet aggregation induced by U-46619 (a TP-receptor agonist, 9, 11-dideoxy-9alpha,11alpha-methanoepoxy prostaglandin F(2alpha)) for 16 h in rat whole blood. Histopathological examination also revealed that Z-335 prevented ferric chloride-induced thrombus formation. These results suggest that Z-335 may prevent ferric chloride-induced arterial thrombosis through its antiplatelet action by blocking TP-receptor activation.

Administration, Oral↗

PubMed2000

Time-sharing contributions of A- and D-type K+ channels to the integration of high-frequency sequential excitatory post synaptic potentials at a model dendrite in rats.

A- and D-type K+ channels (KA and KD channels) have unique physiological properties that play important roles in the integration of excitatory post synaptic potentials (EPSPs) in neuronal dendrites. These functions were analyzed using a computer program, NEURON, to simulate high-frequency sequential synaptic inputs, that can induce long-term potentiation (LTP). We paid close attention to the stability of the reduction of sequential EPSPs. When either KA or KD channels were included in models, the EPSP reduction ratios were less stable than containing both KA and KD channels. When both KA and KD channels were present in the model, the variance of EPSP reduction ratios was significantly smaller in comparison with that in the presence of either KA or KD channels alone. We thus concluded that the co-existence of KA and KD channels is necessary to produce stable EPSPs during the high-frequency synaptic stimulation necessary for induction of LTP.

Animals↗

PubMed2000

Transcriptional regulation of the ATP citrate-lyase gene by sterol regulatory element-binding proteins.

In an attempt to identify unknown target genes for SREBP-1, total RNA from a stable Chinese hamster ovary cell line (CHO-487) expressing a mature form of human SREBP-1a (amino acids 1-487) with a LacSwitch Inducible Mammalian Expression System was subjected to a polymerase chain reaction subtraction method. One of the fragments was found to have 90 and 86% homology with rat and human ATP citrate-lyase (ACL) cDNA, respectively. When Hep G2 cells are cultured under either sterol-loaded or -depleted conditions, expression of the gene is induced approximately 2-3-fold by sterol depletion. To investigate the direct effect of SREBP-1a on transcription, luciferase assays using the promoter of the human ACL gene were performed. These deletion studies indicated that a minimum 160-base pair segment contains the information required for the transcriptional regulation brought about by enforced expression of SREBP-1a. Luciferase assays using mutant reporter genes revealed that SREBP-dependent transcriptional regulation is mediated by two nearby motifs, the SREBP-binding site (a TCAGGCTAG sequence) and the NF-Y-binding site (a CCAAT box). It was confirmed by gel mobility shift assays that recombinant SREBP-1a binds to the sequence. Data from studies with transgenic mice and reporter assays show that the ACL gene promoter is activated by SREBP-1a more strongly than SREBP-2 in contrast to the HMG CoA synthase and LDL receptor gene promoters, which exhibit the same preference for the two factors. Therefore, SREBPs transcriptionally regulates ACL enzyme activity, which generates the cytosolic acetyl CoA required for both cholesterol and fatty acid synthesis.

ATP Citrate (pro-S)-Lyase↗

PubMed2000

cDNA and deduced amino acid sequences of apolipophorin-IIIs from Bombyx mori and Bombyx mandarina.

The cDNA sequence for apolipophorin-III from two strains of Bombyx mori (N4 and P50) and the Japanese and Chinese strains of Bombyx mandarina were determined. Both the cDNA and deduced amino acid sequences of the four apolipophorin-IIIs were highly similar (95-98%). The four Bombyx sequences also showed significant similarity to the sequence of apolipophorin-III from another lepidopteran, Manduca sexta (83-84%), particularly in the five amphipathic alpha-helices that are proposed to play a critical role in the binding of apolipophorin-III to lipophorin. In the coding region, the nucleotide sequences for the Chinese strain of B. mandarina and the P50 strain of B. mori were identical, supporting the suggestion that P50 is the current strain most closely related to the original domesticated strain. The N4 strain of B. mori is more closely related to these two strains than is the Japanese strain of B. mandarina, suggesting that Japanese strain of B. mandarina separated from the Chinese strain of B. mandarina before domestication of B. mori. Arch.

Amino Acid Sequence↗

PubMed2000

Spherical parasporal inclusions of the lepidoptera-specific and coleoptera-specific Bacillus thuringiensis strains: a comparative electron microscopic study.

Four Lepidoptera-specific Bacillus thuringiensis strains that belong to the four H serogroups (serovars sumiyoshiensis, fukuokaensis, darmstadiensis, and japonensis) and a Coleoptera (Scarabaeidae)-specific strain belonging to serovar japonensis were examined for comparative ultrastructure of spherical parasporal inclusions. The prominent feature of the inclusions of the Lepidoptera-specific strains was the existence of thick, highly electron-dense envelopes surrounding a homogeneous protein matrix. The envelopes were 15.0-66.7 nm thick and consisted of 5-12 layers of membrane. This is also the case with inclusions of a Coleoptera-specific strain. The ultrastructure of inclusions from the five strains was in marked contrast to that of the bipyramidal parasporal inclusions produced by a Lepidoptera-specific serovar sotto strain.

Animals↗

PubMed2000

Block of sodium channels by divalent mercury: role of specific cysteinyl residues in the P-loop region.

Divalent mercury (Hg(2+)) blocked human skeletal Na(+) channels (hSkM1) in a stable dose-dependent manner (K(d) = 0.96 microM) in the absence of reducing agent. Dithiothreitol (DTT) significantly prevented Hg(2+) block of hSkM1, and Hg(2+) block was also readily reversed by DTT. Both thimerosal and 2,2'-dithiodipyridine had little effect on hSkM1; however, pretreatment with thimerosal attenuated Hg(2+) block of hSkM1. Y401C+E758C rat skeletal muscle Na(+) channels (mu1) that form a disulfide bond spontaneously between two cysteines at the 401 and 758 positions showed a significantly lower sensitivity to Hg(2+) (K(d) = 18 microM). However, Y401C+E758C mu1 after reduction with DTT had a significantly higher sensitivity to Hg(2+) (K(d) = 0.36 microM) than wild-type hSkM1. Mutants C753Amu1 (K(d) = 8.47 microM) or C1521A mu1 (K(d) = 8.63 microM) exhibited significantly lower sensitivity to Hg(2+) than did wild-type hSkM1, suggesting that these two conserved cysteinyl residues of the P-loop region may play an important role in the Hg(2+) block of the hSkM1 isoform. The heart Na(+) channel (hH1) was significantly more sensitive to low-dose Hg(2+) (K(d) = 0.43 microM) than was hSkM1. The C373Y hH1 mutant exhibited higher resistance (K(d) = 1.12 microM) to Hg(2+) than did wild-type hH1. In summary, Hg(2+) probably inhibits the muscle Na(+) channels at more than one cysteinyl residue in the Na(+) channel P-loop region. Hg(2+) exhibits a lower K(d) value (<1. 23 microM) for inhibition by forming a sulfur-Hg-sulfur bridge, as compared to reaction at a single cysteinyl residue with a higher K(d) value (>8.47 microM) by forming sulfur-Hg(+) covalently. The heart Na(+) channel isoform with more than two cysteinyl residues in the P-loop region exhibits an extremely high sensitivity (K(d) < 0. 43 microM) to Hg(+), accounting for heart-specific high sensitivity to the divalent mercury.

2,2'-Dipyridyl↗

PubMed2000

Structure-physicochemical function relationships of soybean beta-conglycinin constituent subunits

Explore the source record for details and available documents.

Journal Article↗

PubMed2000

Preparation of neoglycoprotein from carp myofibrillar protein and alginate oligosaccharide: improved solubility in low ionic strength medium.

Alginate oligosaccharide (AO) was conjugated with carp myofibrillar protein (Mf) by using the controlled Maillard reaction, and the change in the solubility of Mf in low ionic strength media as affected by the glycosylation was investigated. AO was prepared by degrading sodium alginate using alginate lyase, which was purified from the culture supernatant of Pseudoalteromonas elyakovii. When a lyophilized Mf and AO mixture was incubated at 40 degrees C and 65% relative humidity, the conjugation of AO was confirmed at myosin heavy chain, actin, and tropomyosin. When >30 microg/mg of AO was conjugated to Mf, the protein solubility in a low ionic strength medium was greatly improved without significant loss of available lysine. These results indicate that the conjugation with AO is a superior manner for improving the water solubility of Mf in view of its nutritional aspect.

Alginates↗

PubMed2000

Cloning and bacterial expression of monomeric short-chain dehydrogenase/reductase (carbonyl reductase) from CHO-K1 cells.

Mammalian carbonyl reductase (EC 1.1.1.184) is an enzyme that can catalyze the reduction of many carbonyl compounds, using NAD(P)H. We isolated a cDNA of carbonyl reductase (CHO-CR) from CHO-K1 cells which was 1208 bp long, including a poly(A) tail, and contained an 831-bp ORF. The deduced amino-acid sequence of 277 residues contained a typical motif for NADP+-binding (TGxxxGxG) and an SDR active site motif (S-Y-K). CHO-CR closely resembles mammalian carbonyl reductases with 71-73% identity. CHO-CR cDNA had the highest similarity to human CBR3 with 86% identity. Using the pET-28a expression vector, recombinant CHO-CR (rCHO-CR) was expressed in Escherichia coli BL21 (DE3) cells and purified with a Ni2+-affinity resin to homogeneity with a 35% yield. rCHO-CR had broad substrate specificity towards xenobiotic carbonyl compounds. RT-PCR of Chinese hamster tissues suggest that CHO-CR is highly expressed in kidney, testis, brain, heart, liver, uterus and ovary. Southern blotting analysis indicated the complexity of the Chinese hamster carbonyl reductase gene.

Alcohol Oxidoreductases↗