Biomedical subjects

R Hough

Publications and source records attributed to R Hough.

At least 19 recordsLinked to original sources

PubMed2006

Primary bone lymphoma: a retrospective analysis.

The aim of this study was to retrospectively define those patients with unequivocal primary bone lymphoma presenting to the Sheffield Lymphoma Group and document patient and tumour characteristics and management strategies, and correlate these with survival. Thirty-seven patients were documented from a total of 3148 cases of non-Hodgkin's lymphoma seen over 34 years. There were 17 males and 20 females, with a mean age of 55.4 years (range, 27-78). Pain was the most commonly presented symptom (67.5%), and the pelvis was the most frequently presented site (21.3%). Grade 2 and diffuse large B cell lymphoma comprised the majority of histologies (78.7% and 70.3%, respectively). Treatment was most often with radiotherapy alone (41.8%) or combined with CHOP-like chemotherapy (37.9%). The overall response rate was 56.7%, and 5- and 10-year survival rates were 64.5% and 49.6%, respectively. Univariate analysis showed an age of <60 years and complete response to be favourable prognostic factors. There was a trend toward better survival with combined modality therapy involving CHOP-like chemotherapy. Bone lymphoma has a better survival than other extranodal lymphomas. Younger age and complete response are favourable predictive factors. Combined modality treatment is likely to be the treatment of choice but this remains to be confirmed in large prospective multicentre studies.

Adult↗

PubMed2001

Childhood and adolescent onset conduct disorder: a test of the developmental taxonomy.

Hypotheses generated by a developmental taxonomy that distinguishes between childhood and adolescent onset conduct disorders were tested. Hypotheses predicted that (1) individual and familial factors would be more strongly related to childhood onset conduct disorder, whereas ethnic minority status and exposure to deviant peers would be more strongly related to adolescent onset conduct disorder and (2) individuals with childhood onset disorder would be more likely to commit violent and victim oriented offenses than individuals with adolescent onset conduct disorder. The first hypothesis was strongly supported and the second hypothesis was partially supported. Implications for early identification of youth at risk for chronic offending are discussed.

Adolescent↗

PubMed1999

Comparison of outcomes of acute care in short-term residential treatment and psychiatric hospital settings.

OBJECTIVE: The study compared the demographic and diagnostic characteristics of clients and the outcomes of treatment in five short-term acute residential treatment programs and two acute hospital-based psychiatric programs. METHODS: A total of 368 clients in the short-term acute residential treatment programs and 186 clients in the psychiatric hospital programs participated in an observational study. The study used a repeated-measures design and assessed participants on multiple standardized measures of symptoms and functioning at admission, discharge, and four-month follow-up. Comparisons between the two groups were conducted separately by diagnostic category. Measures included the Brief Symptom Inventory, the Behavior and Symptom Identification Scale-32, the Medical Outcomes Short-Form-36, and the Client Satisfaction Questionnaire-8. RESULTS: The two types of programs admit persons with similar levels of acute distress who have comparable levels of improvement at discharge and an equivalent degree of short-term stability of treatment gains. Costs of treatment episodes were considerably lower for the short-term residential programs, and client satisfaction with the two types of programs was comparable. CONCLUSIONS: Short-term acute residential treatment is a less costly yet similarly effective alternative to psychiatric hospitalization for many voluntary adult patients.

Adult↗

PubMed1995

Service utilization and costs of care for severely mentally ill clients in an intensive case management program.

OBJECTIVE: The study evaluated the effects of an intensive case management model on clients' use of inpatient and outpatient psychiatric care and on the costs of care. METHODS: Ninety clients of a county mental health system who were frequent users of inpatient services were randomly assigned to either an intensive case management group, a traditional case management group, or a control group who received no particular services. Outcome variables measured over a two-year period were number of units used by clients and costs of inpatient care in county and private facilities and various types of outpatient care, including day treatment and use of an emergency psychiatric unit. RESULTS: Clients who received intensive case management had fewer inpatient days and reduced overall costs for mental health services. CONCLUSIONS: Assertive outreach and intensive case management can reduce hospitalizations of clients who are frequent users of inpatient care and can reduce overall mental health care costs. Mental health consumers employed as case management aides can play an important role in the delivery of mental health services, particularly with frequent users of inpatient care.

Adolescent↗

PubMed1995

Risks associated with long-term homelessness among women: battery, rape, and HIV infection.

The purposes of this study were to determine the prevalence of battery, rape, and HIV risk practices in a sample of long-term homeless women and to explore correlates of HIV risk practices. Fifty-three women who had been homeless for at least three months in the last year were interviewed at day and night shelters. The women were demographically similar to other samples of homeless men and women and had similar rates of drug use. However, a higher proportion of homeless women were exposed to battery (91 percent), rape (56 percent), and mental distress, and they had a smaller support network (three people). Eighty-six percent had been battered prior to homelessness. A positive association was found between HIV risk practices and the use of certain drugs and having a protector. A higher level of assertiveness was associated with less HIV risk. The study demonstrated that homeless women are at very high risk of battery and rape. Being homeless may require life-styles that increase the risk of HIV infection and transmission.

Adolescent↗

PubMed1994

Ascorbate modulation of chondrocyte gene expression is independent of its role in collagen secretion.

During development and fracture repair, endochondral bone formation is preceded by an orderly process of chondrocyte hypertrophy and cartilage matrix calcification. Analysis of calcifying versus noncalcifying cartilage has identified several differences in matrix proteins; among these are appearance of a novel collagen, type X, and decreased synthesis of type II collagen, the major component of cartilage matrix. In addition, there is a marked increase in alkaline phosphatase, an enzyme expressed at high levels in all mineralizing tissues. Cultured chondrocytes can be induced to undergo these changes in gene expression and to produce calcified matrix by exposure to ascorbic acid. The mechanism by which ascorbate produces these changes has been examined by analyzing the effect of the vitamin on prehypertrophic chick embryo sternal chondrocytes. Nuclear run-on assays demonstrated that ascorbate alters mRNA levels in chondrocytes by changing the transcription rates. The fact that marked changes in mRNA levels require 1-2 days of ascorbate exposure suggested that the effect of this vitamin on gene transcription may be secondary to other, earlier ascorbate-induced effects. Since cells cultured with ascorbate produce a collagen-enriched matrix, we examined the hypothesis that transcriptional changes were secondary to altered cell-matrix interactions. Chondrocytes were cultured after attachment to tissue culture plastic, in suspension, or on plates coated with collagen type I. Comparison of alkaline phosphatase activity with and without ascorbate addition demonstrated that under all of these conditions, induction of enzyme was dependent on the presence of ascorbate. When plates containing ascorbate-conditioned chondrocyte matrix were used as substrate for naive chondrocytes, the cells continued to require ascorbate for induction of high levels of alkaline phosphatase and type X collagen mRNA. Addition of the hydroxylation inhibitor, 3,4-dehydroproline, caused marked inhibition of collagen secretion as well as accumulation of underhydroxylated collagens within the cells. However, even in the presence of this inhibitor ascorbate was effective in inducing elevated alkaline phosphatase and type X collagen. These results indicate that the ability of ascorbate to induce chondrocyte hypertrophy does not depend on production of a collagen-rich matrix.

Alkaline Phosphatase↗

PubMed1993

Using ECA survey data to examine the effect of job layoffs on violent behavior.

OBJECTIVE: The study examined two hypotheses: that being laid off increases the likelihood of violence and that being employed in an industry in which employment is unexpectedly low decreases the likelihood of violence. METHODS: Logistic regression analyses were used to examine data for more than 4,000 persons who participated in initial and follow-up interviews as part of the Epidemiologic Catchment Area survey. Data for persons who were working and not violent at the time of the initial interview but who were unemployed at reinterview were examined, as were data for persons who remained employed in industries with low employment levels. RESULTS: The risk of violent behavior of those who were laid off was nearly six times higher than that of their employed counterparts. Controlling for concurrent psychiatric disorder did not reveal a lower risk. The risk of violent behavior was reduced among those who remained employed in industries where layoffs were occurring. CONCLUSIONS: Economic contraction seems to affect violence in the community in two countervailing processes--one process increases violence and one reduces it. However, the net effect may well be that violence decreases in communities experiencing economic contraction.

Adolescent↗

PubMed1993

Job loss and alcohol abuse: a test using data from the Epidemiologic Catchment Area project.

The hypothesis that job loss affects the incidence of clinically significant alcohol abuse is tested using panel data from the Epidemiologic Catchment Area project. Results suggest that the incidence of clinically significant alcohol abuse is greater among those who have been laid off than among those who have not. However, employed persons in communities in which total employment is unexpectedly low are at reduced risk of becoming alcohol abusers. The implications of the results for economic policy and for mental health services are discussed briefly.

Adult↗

PubMed1991

Lifetime and current prevalence of specific psychiatric disorders among Vietnam veterans and controls.

To determine if Vietnam theater veterans were more likely than controls to have a specific psychiatric disorder other than posttraumatic stress disorder, the rates of specific psychiatric disorders were estimated using the Diagnostic Interview Schedule for national samples of veterans who served in Vietnam, other veterans of the Vietnam era, and matched civilian controls. Overall, there were few differences in rates of disorder between theater and other veterans; there were somewhat more differences between theater veterans and civilians. There were striking differences, however, in rates for most disorders, both lifetime and current, between male theater veterans with high levels of exposure to war zone stress and other male veterans or civilians. Female veterans exposed to high levels of war zone stress also had higher rates than other female respondents for several disorders.

Adult↗

PubMed1989

Proteolysis in heat-stressed HeLa cells. Stabilization of ubiquitin correlates with the loss of proline endopeptidase.

When intact HeLa cells were incubated at 45 degrees C, there was progressive inactivation of proline endopeptidase. Rapid loss of the enzyme did not occur in extracts maintained at 45 degrees C. Since Western blots of sodium dodecyl sulfate-polyacrylamide gel electrophoresis gels showed no decrease in the immunoreactive 70-kDa proline endopeptidase band, its in vivo disappearance apparently results from irreversible denaturation or modification. Loss of proline endopeptidase activity was paralleled by reduced degradation of injected ubiquitin and bovine serum albumin. In contrast, proteolysis of injected lysozyme or pancreatic trypsin inhibitor was barely affected. Electrophoretic analysis of ubiquitin or bovine serum albumin retrieved from heated HeLa cells showed that the injected proteins were intact. Thus, the presence of proline endopeptidase appears to be required for initial cleavage of these two substrates, but it has not been shown that the enzyme is directly responsible. Selective stabilization of a subset of the injected proteins does, however, demonstrate the existence of distinct proteolytic pathways in HeLa cytosol.

Animals↗

PubMed1989

Circular pancreatic trypsin inhibitor. A novel substrate for studies on intracellular proteolysis.

Several recent studies indicate that substrates for ubiquitin-dependent proteolysis must possess unblocked alpha-amino termini. To examine further the importance of free amino groups for proteolytic susceptibility we selected pancreatic trypsin inhibitor (PTI) as a test substrate. PTI can be circularized to form cPTI, a molecule that lacks alpha-amino groups in the absence of an endoproteolytic cleavage. We compared the breakdown of radioiodinated PTI and cPTI in rabbit reticulocyte lysate and found that cPTI was not stabilized relative to PTI. In addition, proteolysis of PTI or cPTI was not inhibited upon conversion of their lysine residues to homoarginine. However, neither degradation of PTI nor cPTI required ATP, and ubiquitin conjugation to either molecule was minor relative to known substrates of the ubiquitin pathway. Thus, PTI and cPTI are cleaved by an ATP-independent endoprotease(s) that does not require the substrate to be ubiquitinated. Such an activity was identified in low salt fractions obtained upon DEAE chromatography of reticulocyte lysate. The ubiquitin/ATP-dependent protease and another large multisubunit protease, both of which elute from DEAE-Fractogel at higher salt concentrations, do not degrade PTI or cPTI. Although monomeric PTI was rapidly degraded in reticulocyte lysate, cross-linked PTI molecules were stable both in reticulocyte lysate and following introduction into cultured cells using red blood cell-mediated microinjection. Thus, increased rates of turnover do not necessarily correlate with greater molecular mass of the substrate.

Animals↗

PubMed1987

Purification of two high molecular weight proteases from rabbit reticulocyte lysate.

We have purified two high molecular weight proteases approximately 400-fold from rabbit reticulocyte lysate. Both enzymes hydrolyze 125I-alpha-casein and 4-methylcoumaryl-7-amide peptides with tyrosine, phenylalanine, or arginine at the P1 position. Both are inhibited by hemin, thiol reagents, chymostatin, and leupeptin. They differ, however, by other criteria. Degradation of 125I-lysozyme-ubiquitin conjugates and succinyl-Leu-Leu-Val-Tyr-4-methylcoumaryl-7-amide by the larger 26 S protease is stimulated by ATP. Based on sedimentation, gel filtration, and nondenaturing polyacrylamide gel electrophoresis, the ATP-dependent protease has a molecular weight of 1,000,000 +/- 100,000 and is a multisubunit complex. The smaller 20 S protease has a molecular weight of 700,000 +/- 20,000 and is composed of 8-10 separate subunits with Mr values between 21,000 and 32,000. It does not require nucleotides for degradation of protein or peptide substrates. This smaller enzyme is similar, if not identical, to the "multicatalytic proteinase complex" first described by Wilk and Orlowski (Wilk, S., and Orlowski, M. (1983) J. Neurochem. 40, 842-849).

Adenosine Triphosphate↗

PubMed1986

Ubiquitin-lysozyme conjugates. Purification and susceptibility to proteolysis.

To produce ubiquitinated substrates for studies on ATP-dependent proteolysis, 125I-lysozyme was incubated in hemin-inhibited rabbit reticulocyte lysates. A portion of the labeled molecules became linked to ubiquitin in large covalent complexes. When these were partially purified and returned to uninhibited lysates containing ATP, the conjugated lysozyme molecules were degraded 10 times faster than free lysozyme. Purification of covalently modified lysozyme from hemin-inhibited lysates containing 125I-ubiquitin and 131I-lysozyme confirmed that both molecules were present in the complexes. The doubly labeled conjugates also permitted us to determine the fate of each molecule in uninhibited lysates. Besides degradation of lysozyme, there was a progressive release of intact lysozyme molecules from the complexes. This disassembly, which was the only fate of the complexes in the absence of ATP, proceeded through a series of smaller intermediates, several having molecular weights expected for ubiquitin-lysozyme conjugates, and eventually free lysozyme was regenerated. The behavior of labeled ubiquitin was similar, though not identical, to that of lysozyme. Even in lysates containing ATP ubiquitin emerged from the complex undegraded. Furthermore, ubiquitin was present in a greater number of species than was lysozyme. The demonstration that ubiquitin-lysozyme conjugates are rapidly degraded provides support for the hypothesis of Hershko, Rose, Ciechanover, and their colleagues that a key function of ubiquitin is to modify the proteolytic substrate. Further support for the hypothesis is presented in the following paper where we show that the conjugated lysozyme molecules are substrates for an ATP-dependent protease that does not degrade free lysozyme.

ATP-Dependent Proteases↗

PubMed1986

Ubiquitin-lysozyme conjugates. Identification and characterization of an ATP-dependent protease from rabbit reticulocyte lysates.

Ubiquitin-lysozyme conjugates have been used as substrates to identify an ATP-dependent protease from rabbit reticulocyte lysates. The enzyme, which has been partially purified by DEAE chromatography and glycerol gradient centrifugation, has an apparent molecular weight greater than 600,000 based on sedimentation and gel filtration. Whereas it degrades conjugated lysozyme molecules in the presence of ATP, the protease does not degrade free lysozyme molecules even upon addition of ubiquitin, lysozyme-ubiquitin conjugates, and ATP. Degradation of lysozyme conjugates is independent of added ubiquitin and occurs in fractions incapable of ubiquitin conjugation. Proteolysis is maximal at pH 7.8, inhibited by hemin, N-ethylmaleimide, or aurintricarboxylic acid, and proceeds with an apparent Arrhenius activation energy in the range of 27 +/- 5 kcal/mol. These properties are similar to those observed for the degradation of lysozyme conjugates in lysates indicating that the partially purified protease catalyzes the "second" ATP-utilizing reaction identified previously (Hough, R., and Rechsteiner, M. (1984) Proc. Natl. Acad. Sci. U. S. A. 81, 90-94; Hershko, A., Leshinsky, E., Ganoth, D., and Heller, H. (1984) Proc. Natl. Acad. Sci. U. S. A. 81, 1619-1623; Tanaka, K., Waxman, L., and Goldberg, A. L. (1983) J. Cell Biol. 96, 1580-1585).

ATP-Dependent Proteases↗

PubMed1986

Depressive symptoms and their correlates among immigrant Mexican women in the United States.

Correlates of depressive symptomatology and caseness are examined for a survey sample of N = 1825 poor Mexican immigrant women in San Diego County, California. The Center for Epidemiologic Studies--Depression (CES--D) checklist is tested against a variety of demographic variables as well as health status and service utilization rates. Statistically significant associations were found between CES--D and education, years in the United States, income, marital status and number of adults in household. Also significant were associations with health status, confidant support and recent, traumatic life event. Utilization rates point to medical doctors as the major source of formal treatment and a heavy reliance on family and friends. The implications of the high disorder rates for diagnosis and treatment among immigrants are discussed.

Adult↗

PubMed1984

What determines the degradation rate of an injected protein?

The fusion of cultured mammalian cells to red blood cells loaded with specific proteins provides a powerful system for the study of intracellular proteolysis. During the past four years the degradation rates of more than 30 proteins have been examined after their injection into HeLa cells. Results from these studies support the legitimacy of the microinjection approach. They also provide insight into the mechanism of intracellular proteolysis.

Animals↗

PubMed1984

Effects of temperature on the degradation of proteins in rabbit reticulocyte lysates and after injection into HeLa cells.

Bovine serum albumin, pyruvate kinase, hemoglobin, and the Fc fragment of IgG were labeled and introduced into HeLa cells by erythrocyte-mediated microinjection. Degradation of the injected proteins was then measured in cells cultured at temperatures between 6 degrees C and 37 degrees C. Arrhenius plots revealed a constant Ea of 27 +/- 5 kcal/mol over this temperature interval. Similarly, the apparent Ea for the degradation of long-term endogenously labeled HeLa proteins was 22-26 kcal/mol. Both local protein unfolding and proteolysis by defined enzymes, such as trypsin or papain, proceed with EaS between 5 and 15 kcal/mol. The 2-fold higher values obtained in this study indicate that protein unfolding or simple proteolysis is not rate limiting in the degradation of injected or long-lived endogenous HeLa proteins. Moreover, the relatively uniform EaS suggest that a similar biochemical event is rate limiting in the degradation of a specific protein independent of its half-life. This event may involve a reaction in the ATP-dependent proteolytic pathway from rabbit reticulocyte lysates because we observed that EaS for ATP-dependent proteolysis in this system were also 27 +/- 5 kcal/mol.

Animals↗

PubMed1984

Attention to stimuli, verbal labeling, and question asking in referential communication.

This study evaluated the effects of age, the dyad's attention to and verbal labeling of target and nontarget stimuli, and listener instructions to ask questions on referential communication in 48 five-year-old and 48 eight-year-old dyads. A MANOVA for dyad activities indicated both age and dyad-activities differences. The dyads that located and verbally labeled the critical attributes were superior to the dyads that simply located the critical attributes and to control dyads on speaker performance. A MANOVA for listener instructions to ask questions yielded no age differences on the number of questions asked and no interaction between age and instructions to ask questions. It indicated that listeners instructed to ask questions and control listeners differed on the number of questions asked but not on communication accuracy.

Attention↗