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Objective: To examine several hospital-based procedures for systematic utilization differences between the genders and among ethnic groups (Asian, black, Latino, and white). Methods: California hospital discharges in 1989 and 1990 were sampled by principal diagnosis. Odds ratios for treatment by demographic class were estimated for heart transplantation, kidney transplantation, extracorporeal shockwave lithotripsy, hip replacement, carotid endarterectomy, coronary artery bypass grafting, percutaneous transluminal coronary angioplasty, pacemaker implant, and automatic cardioverter-defibrillator implant. Logistic regression controlled for insurance status, age, diagnosis, and comorbidity count. Results: The following results were statistically significant P

Constitutively activated signal transducers and activators of transcription (Stats), in particular Stat3 and Stat5, have been demonstrated to directly contribute to oncogenesis by stimulating cell proliferation and preventing apoptosis in various cancers. Stat3 is essential in mammary gland epithelial cell apoptosis and involution, whereas Stat5 is well established as a key factor in mammary epithelial cell growth and differentiation. Crosstalk between Stats and estrogen receptor (ER) has been demonstrated by several laboratories and we have focused on the role of Stat5 in ER-positive breast cancer. Using immunohistochemical techniques, we examined the expression of Stat3 and Stat5 in 517 human breast cancer tissues and analyzed their significance for prognosis and prediction of response to endocrine therapy. Stat5 expression was significantly correlated with histological grade (P< 0.0001), ER (P= 0.02), and progesterone receptor (P= 0.026) expression. There was no difference between Stat3 expression and clinicopathological factors. In 346 patients with ER-positive breast cancer, patients with Stat5 positive tumors had significantly increased overall survival (P= 0.0009) in multivariate analysis. There were 70 patients who received endocrine therapy as first-line treatment for metastatic breast cancer at relapse. The patients whose primary breast tumors were Stat5 positive, had significantly better response to endocrine therapy (P= 0.04), and longer survival after relapse (P= 0.0003), than those whose tumors were Stat5 negative. The present study demonstrates for the first time that Stat5 is a predictive factor for endocrine therapy response and a strong prognostic molecular marker in ER-positive breast cancer. Our data suggest that the expression of Stat5 is helpful in selecting patients who may benefit from endocrine therapy.

Abstract: Bombyx mori is a female-heterogametic organism (female, ZW; male, ZZ) that appears to have a putative feminizing gene (Fem) on the W chromosome. The paternally transmitted mutant W chromosome, Df(p Sa + p W + od )Fem, derived from the translocation-carrying W chromosome (p Sa + p W + od ), is inert as femaleness determinant. Moreover, this Df(p Sa + p W + od )Fem chromosome has been thought to have a female-killing factor because no female larvae having the Df(p Sa + p W + od )Fem chromosome are produced. Initially, to investigate whether the Df(p Sa + p W + od )Fem chromosome contains any region of the W chromosome or not, we analyzed the presence or absence of 12 W-specific RAPD markers. The Df(p Sa + p W + od )Fem chromosome contained 3 of 12 W-specific RAPD markers. These results strongly indicate that the Df(p Sa + p W + od )Fem chromosome contains the region of the W chromosome. Moreover, by using phenotypic and molecular markers, we confirmed that the Df(p Sa + p W + od )Fem chromosome is connected with a partially deleted Z chromosome and that this fused chromosome behaves as a Z chromosome during male meiosis. Furthermore, we demonstrated that the ZZW-type triploid female having the Df(p Sa + p W + od )Fem chromosome is viable. Therefore, we concluded that the Df(p Sa + p W + od )Fem chromosome does not have a female-killing factor but that partial deletion of the Z chromosome causes the death of the ZW-type diploid female having the Df(p Sa + p W + od )Fem chromosome. Additionally, our results of detailed genetic analyses strongly indicate that the female-killing chromosome composed of the Df(p Sa + p W + od )Fem chromosome and deleted Z chromosome was generated by translocation between the Z chromosome and the translocation-carrying W chromosome, p Sa + p W + od .

Abstract The sex chromosome constitution of the silkworm, Bombyx mori, is ZW in the female and ZZ in the male. Very little molecular information is available about the Z chromosome in Lepidoptera, although the topic is interesting because of the absence of gene dosage compensation in this chromosome. We constructed a 320-kb BAC contig around the Bmkettin gene on the Z chromosome in Bombyx and determined its nucleotide sequence by the shotgun method. We found 13 novel protein-coding sequences in addition to Bmkettin. All the transposable elements detected in the region were truncated, and no LTR retrotransposons were found, in stark contrast to the situation on the W chromosome. In this 320-kb region, four genes for muscle proteins (Bmkettin, Bmtitin1, Bmtitin2, and Bmprojectin) are clustered, together with another gene (Bmmiple) on the Z chromosome in B. mori; their orthologs are also closely linked on chromosome 3 in Drosophila, suggesting a partial synteny. Real-time RT-PCR experiments demonstrated that transcripts of 13 genes of the 14 Z-linked genes found accumulated in larger amounts in males than in female moths, indicating the absence of gene dosage compensation. The implications of these findings for the evolution and function of the Z chromosome in Lepidoptera are discussed.

Abstract. Kynurenine 3-monooxygenase (KMO, EC 1.14.13.9), which catalyzes the oxidation of kynurenine to 3-hydroxykynurenine, is involved in the synthesis of ommochrome pigments in insects. A silkworm mutant, white egg 1 (w-1), has been shown to be deficient in this enzyme activity. The mutant is characterized morphologically by its white eyes and the fact that the females lay white eggs. To analyze the relationship between the KMO gene and the mutation, we first determined the entire sequence of a full-length 2.0-kb cDNA and examined its expression pattern in the wild type. The cDNA sequence contains one ORF encoding a polypeptide of 456 amino acids, and transcripts were detected in the larval Malpighian tubules and the pupal ovaries, but not in other tissues. Southern analysis and nucleotide sequencing showed that the KMO gene is present in a single copy and consists of ten exons distributed over a 16-kb region. Comparison of the transcripts between the wild type and mutant silkworms showed that the wild type expressed a single transcript, whereas the mutant exhibited markedly reduced amounts of two transcripts with sizes of 2.0 kb and 1.8 kb. Nucleotide sequence analysis of these mutant transcripts indicated that sequences corresponding to the ninth and tenth exons were missing. Inverse PCR and Southern analysis of the mutant gene demonstrated that the corresponding genomic region was deleted in the w-1 mutant.

To characterize the structural features common toPao-like retrotransposons, we analyzed two lambda phage clones which contain thePao-like elements from the silkworm speciesBombyx moriandB.mandarina, and copies ofPaoitself andninjaofDrosophila simulans, amplified by PCR. We previously identified two randomly amplified polymorphic DNAs (RAPDs), W-Kamikaze and W-Yamato, fromB.moriandB.mandarina, which are part of two novelPao-like retrotransposons,KamikazeandYamato, respectively. Complete characterization of these and other elements of this group reported here shows thatPao-like elements have common features that distinguish them from the other groups of LTR-retrotransposons. While the elements of the Ty1-copiagroup encode only one cysteine and histidine (Cys) motif in theirgag-like region, thePao-like elements specify three Cys motifs. The highly conserved D(35)E motif in the integrase domain of the retrotransposon polyprotein seems to be conserved inPao-like elements, but the number of amino acid residues between D and E varies and is greater than 35. A comparison of the deduced amino acid sequences of the reverse transcriptase domain revealed that thePao-like elements are members of neither the Ty1-copianor thegypsy-Ty3 groups. Therefore, we confirmed that the long-terminal-repeat (LTR) retrotransposons should be divided into three major groups (or families), namely the Ty1-copia,gypsy-Ty3, andPao-like groups.

Condenser microphones (MIC) have been widely used in mechanomyography, together with accelerometers and piezoelectric contact sensors. The aim of the present investigation was to clarify the mechanical variable (acceleration, velocity or displacement) indicated by the signal from a MIC transducer using a mechanical sinusoidal vibration system. In addition, the mechanomyogram (MMG) was recorded simultaneously with a MIC transducer and accelerometer (ACC) during voluntary contractions to confirm the mechanical variable reflected by the actual MMG and to examine the influence of motion artifact on the MMG. To measure the displacement-frequency response, mechanical sinusoidal vibrations of 3 to 300 Hz were applied to the MIC transducer with different sizes of air chambers (5, 10, 15 and 20 mm in diameter and 15, 20 or 25 mm long). The MIC transducer showed a linear relationship between the output amplitude and the vibration displacement, however, its frequency response declined with decreasing diameter and decreasing length of the air chamber. In fact, the cut-off frequency (−3 dB) of the MIC transducer with the 5-mm-diameter chamber was 10, 8 and 4 Hz for the length 15, 20 and 25 mm, respectively. The air chamber with at least a diameter of 10 mm and a length of 15 mm is recommended for the MIC transducer. The sensitivity of this MIC transducer arrangement was 92 mVμm−1when excited at 100 Hz. During voluntary contraction, the amplitude spectral density function of the MMG from the MIC transducer resembled that of the double integral of the ACC transducer signal. The angle of the MIC transducer was delayed by 180° in relation to the ACC transducer signal. The sensitivity of the MIC transducer was reduced to one-third because of the peculiar volume change of air chamber when the MMG was detected on the surface of the skin. In addition, the MIC transducer was contaminated by a smaller motion artifact than that from the ACC transducer. The maximal peak amplitude of the MIC and ACC transducer signal with the motion artifact was 7.7 and 12.3 times as much as the RMS amplitude of each signal without the motion artifact, respectively. These findings suggest that the MIC transducer acts as a displacement meter in the MMG. The MIC transducer seems to be a possible candidate for recording the MMG during dynamic muscle contractions as well as during sustained contractions.

Clinical practice guidelines are expanding their scope of authority from clinical decision making to collective policy making, and promise to gain ground as resource allocation tools in coming years. A close examination of how guidelines approach patient selection criteria offers insight into their ethical implications when used as resource allocation or rationing instruments. The purposes of this paper are: a) to examine the structure of allocative reasoning found in clinical guidelines; b) to identify the ethical principles implied and compare how guidelines enact these principles with how explicit systems-level rationing exercises and health policy analyses have approached them; and c) to offer some preliminary suggestions for how these ethical issues might be addressed in the process of guideline development. The resulting framework can be used by guideline developers and users to understand and address some of the ethical issues raised by guidelines for the use of scarce technologies.

Abstract:: Osteoblast deficit plays a principal role in the development of diabetic osteopenia. We have previously reported that high glucose conditions impair the function of osteoblast-like MG-63 cells. This study was performed to assess the sensitivity of osteoblasts to 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) in patients with type 2 diabetes without insulin deficiency or overt diabetic complications. During stimulation with 1,25(OH)2D3 at 2.0 mg/day for 6 consecutive days in 9 type 2 diabetic patients, serum levels of bone alkaline phosphatase (BALP), osteocalcin (OC) and the carboxyterminal propeptide of type 1 procollagen, and the urinary excretion of pyridinoline and deoxypyridinoline (DPYR), were monitored. As parameters of glycemic control, the mean level of fasting plasma glucose (mFPG) throughout the 1,25(OH)2D3 stimulation test and the level of HbA1C were used. 1,25(OH)2D3 increased serum 1,25(OH)2D significantly by day 2, which was followed by a significant reduction in the serum level of intact parathyroid hormone. The maximal increment of serum OC adjusted for that of 1,25(OH)2D was negatively correlated with both mFPG and HbA1C levels (p50.05). Furthermore, the magnitude of 1,25(OH)2D3-induced bone resorption, as reflected by the maximal increase in urinary DPYR excretion, was negatively correlated with the mFPG level (p50.05). Basal BALP tended to be negatively correlated with HbA1C, although not to a significant extent. In conclusion, our findings would indicate that poor glycemic control impairs the responses of osteoblasts and osteoclasts to 1,25(OH)2D3 in normo-insulinemic type 2 diabetic patients.

Abstract: The piezoelectric contact sensor has been widely utilised in mechanomyography (MMG). The authors aim to clarify the mechanical variables (i.e. acceleration, velocity or displacement) reflected by the MMG signal detected with a piezoelectric contact sensor (PEC), and compare the results with those obtained simultaneously by an accelerometer (ACC). To measure the acceleration-frequency response, a mechanical sinusoidal excitation of 5 to 300 Hz at a constant magnitude of 0.01 G was applied to the two transducers. The acceleration-frequency response of the ACC transducer was confirmed to be almost flat. The PEC without any restriction of the transducer housing (including the combined seismic mass) demonstrated a similar response to the ACC transducer. The PEC transducer output with restricted housing decreased with increasing sinusoidal frequency and an attenuation slope of −40 dB/decade and phase angle of −180 degrees. The voluntary MMG signal during isometric knee extension was recorded simultaneously with the two transducers. The amplitude spectral density distribution of the MMG from the PEC transducer was narrow and the mean frequency was approximately one-half that obtained from the ACC tranducer. The amplitude spectral density distribution with the PEC transducer resembled that of the double integral over time of the ACC transducer signal. The phase angle of the PEC transducer signal was different from that of the ACC transducer signal by approximately −180°. These results suggest that the PEC transducer acts as a displacement meter of muscle vibration. In addition, differences in the MMG frequency components relating to the transducer type must be taken into consideration when investigating the mechanical activity of muscle.

By using porcine elastase I cDNA as a probe, we have isolated two different but closely related cDNAs encoding elastase-like proteases from a human pancreatic cDNA library. The amino acid sequences deduced from the cloned cDNA sequences showed 56-61% identity with those of both pancreatic elastases I and II, similar to the homology between elastases I and II. The active form of the elastase-like proteases appeared to be composed of 242 amino acids and preceded by a signal peptide and propeptide of 28 amino acids. Dot blot analysis of various tissue mRNAs demonstrated that the genes for the cloned cDNAs are expressed at a high level only in the pancreas. In addition, sequence analysis of the cloned genomic genes corresponding to one of the cDNAs showed that they are members of the elastase gene family. These results indicate that the two enzymes encoded by the cDNAs should be classified into a third class of elastase isozyme. Therefore, we designated them as human pancreatic elastases IIIA and IIIB. They strongly resembled cholesterol-binding pancreatic protease, suggesting that they may possess not only a digestive function but also function(s) related to cholesterol metabolism or transport in the intestine.

Genetic and biochemical analyses were performed on the cytoplasmic cap-binding complex (eukaryotic initiation factor (eIF) 4F) of Schizosaccharomyces pombe. Genomic and cDNA sequencing of the S. pombe gene (tif1) encoding the cap-binding component eIF4E revealed the presence of two introns in a reading frame of 219 codons. The encoded sequence of 218 amino acids shows a greater degree of identity to the mammalian eIF4E sequence than does its counterpart from Saccharomyces cerevisiae. In particular, unlike its S. cerevisiae counterpart, S.pombe eIF4E has a C-terminal Ser209 within the motif KSGST that is a site of phosphorylation in hamster and rabbit eIF4E. Of relevance to its potential regulatory role, eIF4E was found to be encoded by an mRNA with a six-nucleotide leader and to be of low abundance in vivo. Cross-linking experiments identified S. pombe eIF4E as the major cap-binding protein while a further protein, p36, also showed cap-dependent binding. eIF4A was not associated with the cap-binding complex. While S. pombe eIF4E was shown capable of binding S. cerevisiae p20, an equivalent protein was absent from the eIF4F complex isolated from S. pombe cells. S. pombe 4F therefore shows a remarkable combination of structural and functional properties, some of which it shares with its higher and its lower eukaryotic counterparts.

SDF-1 is a member of the CXC chemokines. In contrast to other chemokines that are induced by inflammation, SDF-1 is constitutively produced by stromal cells. In order to investigate the physiological roles of SDF-1, we constructed a fusion protein, SDF-1-C_γ1, composed from murine SDF-1α and the constant region of human IgG. SDF-1-C_γ1 stained EL-4 T lymphoma cells and the staining was blocked by rhSDF-1β. The expression levels of SDF-1R altered along with the T cell maturation. Most c-kit⁺ hematopoietic precursors in fetal liver in gestational day (GD) 14.5 embryo were SDF-1R^-, while c-kit⁺ double-negative (DN) thymocytes in the embryo were positive for SDF-1R. The receptor expression increased along with T cell maturation up to double-positive (DP) cell stage. Interestingly, SDF-1R expression was down-modulated after positive selection; CD69⁺CD3^hi DP and CD3^hi single-positive thymocytes were SDF-1R^-/lo. Northern blot analysis demonstrated that SDF-1 and CSCR4 mRNAs were abundantly expressed in the thymuses of embryo and adult mice. These results demonstrate that SDF-1R expression is involved in T cell development in the thymus, particularly in positive selection.

Hemodynamic responses and hormonal changes induced by lower body negative pressure (LBNP) were measured in bedridden patients with severe disabilities to identify their cardiovascular function. After a control period of 5 minutes supine, each subject underwent a LBNP test of -20 mmHg for 5 minutes. Disabled patients were classified into two groups: Group HI consisted of the members who had a blood pressure response to LBNP exposure similar to normal control subjects, and group H2 patients displayed a greater reduction in blood pressure than the normal response. Both disabled groups demonstrated a significantly higher level of resting heart rate as well as a smaller stroke volume and cardiac output than normal subjects. Exposure to LBNP in disabled patients produced a smaller decrement in stroke volume and cardiac output than in normal subjects. The expected increase in heart rate for the compensatory effect was not observed in the HI group, and a decreased heart rate lower than resting values was measured in the H2 group. The norepinephrine response of the disabled groups was found to be insufficient compared with normal subjects. It is suggested that cardiovascular deconditioning of disabled patients is caused not only by a decrease in total blood volume, but also by impairment of baroreflex activity both centrally and peripherally due to the patient's extremely prolonged recumbency.

The purpose of this investigation was to identify the cardiovascular response to an orthostatic tolerance test in severely disabled patients during prolonged recumbency in a sitting position and under lower body negative pressure. The disabled subjects were categorized into three groups according to the degree of their exposure to gravitational stress in daily living and their past history of posture and motor ability. The members of one group (ST1) were now supported in a sitting position during present daily living and were able to sit or stand independently in the past. The subjects in the second group (ST2) were never able to sit or stand independently but were also supported in an orthostatic posture during daily living as were ST1 group members. The third group (BR) was bedridden fully from birth and had no experience, ever, of orthostatic forces during daily living. A marked decrease in photoplethysmogram of the big toe in the change from the resting supine to the sitting condition, which represented a reduction in peripheral blood flow and concomitant venous return, was observed in all the disabled groups compared with the response of normal subjects to the same procedure. A compensatory increase in heart rate was observed in the ST1 and ST2 groups but the BR group did not show this. Mean blood pressure in the normal group remained unchanged, whereas the disabled groups demonstrated a progressive decrease in mean blood pressure in the order BR > ST2 > ST1 by reason of the varying degree of their daily orthostatic stimulus. It was concluded that cardiovascular regulation in the bedridden disabled was associated both with their present exposure to normal gravitational forces during daily living and with their past history of posture and motor ability.

Twenty N,N'-dialkylpolymethylendiamine derivatives were synthesized, and a study was made of their antimicrobial activities in vitro against four oral microorganisms which are related to dental caries. The maximum activity was shown by N,N'-dinonyl or N,N'-didecyl derivatives among the complete homologous series of compounds studied.

We have isolated a @b-tubulin-encoding cDNA clone of Bombyx mori from testes and determined the nucleotide sequence. Northern analyses showed that its expression is testis-specific and most active in the pupal stage.

Motivation: A whole set of Expressed Sequence Tags (ESTs) from the Sf9 cell line of Spodoptera frugiperda is presented here for the first time. By this way we want to identify both conserved and specific genes of this pest species. We also expect from this analysis to find a class of protein sequences providing a tool to explore genomic features and phylogeny of Lepidoptera. Results: The ESTs display both housekeeping as well as developmentally regulated genes, and a high percentage of sequences with unknown function. Among the identified ORFs, almost all ribosomal proteins (RPs) were found with high EST redundancy and hence sequence accuracy. The codon usage found among RP genes is in average surprisingly much less biased in Lepidoptera than in other organisms. Other Spodoptera genes also displayed a low bias, suggesting a general genome expression feature in this Lepidoptera. We also found that the L35A and L36 RP sequences, respectively, display 40 and 10 amino-acid insertions, both being present only in insects. Sequence analysis suggests that they are probably not subjected to a strong selective pressure and may be good phylogenetic markers for Lepidoptera. Most interestingly, the Lepidoptera sequences of 9 RP genes displayed a specific signature different from the canonical one. We conclude that the RP family allows valuable comparative genomics and phylogeny of Lepidoptera. Availability: All EST sequence data are available from the private ‘Spodo-Base’ upon request.

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