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Biomedical subjects

M Cutler

Publications and source records attributed to M Cutler.

At least 19 recordsLinked to original sources
PubMed1997

Psychosocial outcome of children evaluated for short stature.

OBJECTIVE: To assess the psychosocial functioning of adults who were evaluated as children for short stature and were not treated with human growth hormone. DESIGN: Inception cohort study. SETTING: Hospital-based pediatric endocrinology clinic. PARTICIPANTS: From 1975 to 1980, medical record review indicated that 181 of the children referred to our clinic for concerns about short stature were non-growth hormone deficient. In 1992 and 1993, we were able to recruit 35 of these patients for a follow-up study. Eligible subjects were at least 18 years of age at the time of follow-up. MAIN OUTCOME MEASURES: Standardized self-report questionnaires assessed various domains of psychosocial adjustment. Also, a brief test of intellectual functioning was administered and subjects underwent a semistructured in-person interview to evaluate pragmatic functioning and experiences associated with short stature. RESULTS: Few significant differences between the study sample and standardization samples were found on measures of psychosocial and intellectual functioning. Within-group childhood height during the first evaluation appointment was not significantly associated with most adult measures of psychosocial adjustment. Shorter adult stature was significantly associated with lower educational achievement, lower self-esteem, and greater emotional distress. CONCLUSIONS: The absence of significant psychosocial distress or impairment in these subjects brings into question one basis for hormonal treatment for non-growth hormone deficient short stature; that short stature in childhood is likely to lead to psychological dysfunction in adulthood. The results, however, also suggest that shorter stature in adulthood may constitute a psychosocial stressor, increasing vulnerability across several domains.

Adaptation, Psychological↗
PubMed1997

Administration of Epoetin alfa. Case study of the anemic patient.

Improving patient outcomes by achieving a stable Hct in the higher end of the target Hct range of 30% to 36% is the primary goal of anemia management and Epoetin alfa therapy. Recently, attention has been focused on the potential differences between subcutaneous (s.c.) and intravenous (i.v.) administration. Although some patients may require less Epoetin alfa when it is administered by the s.c. route, many patients require the same dose or more due to the significant heterogeneity in response. To ensure that therapeutic outcomes are maintained or improved, clinicians should evaluate both staff considerations and individual patient tolerance and response when determining the optimal route of administration.

Anemia↗
PubMed1997

Retention in substance abuse treatment. Role of psychiatric symptom severity.

The authors investigated the association between psychiatric symptom severity and subsequent treatment retention among substance abusers. The Symptom Check List-90-R was administered, after admission to an addiction treatment facility, to 308 male and 106 female clients with moderate-to-severe substance abuse problems. Mean scores on nine symptom and three summary scales were computed. Controlling for other sociodemographic and treatment variables, somatization was significantly associated with dropout from specialized outpatient and inpatient treatment programs. This study, however, suggests that psychopathologic symptom severity at admission has only limited utility in predicting subsequent treatment retention among substance abusers with overall moderate levels of psychological distress.

Adult↗
PubMed1996

O-linked glycosylation modifies CD44 adhesion to hyaluronate in colon carcinoma cells.

CD44 alternative splicing patterns differ between normal and malignant tissue, and accordingly, modulation of CD44 splicing has received the most attention in studies that have examined the role of CD44 in tumor progression. Many investigators have examined functional differences between individual CD44 alternative splice variants. However, specific CD44 isoforms function uniquely depending on the type of cell on which they are expressed, thereby suggesting that additional tissue-specific mechanisms regulate CD44 function. In the present study we have demonstrated that colon carcinoma cells modify CD44 with O-linked glycosyl groups, and blockade of this glycosylation enhances their CD44-mediated adhesion to hyaluronate. This enhancement is attributable principally to CD44H (CD44s) rather than high molecular weight CD44 variants. Use of site-directed mutant CD44H cDNA transfectants demonstrated that CD44 O-linked glycosylation modulates interaction between hyaluronate and the B loop domain of CD44. The influence of glycosylation on CD44 function in colon carcinoma cells is specific to the presence of O-linked sugars; inhibition of N-linked glycosylation had minimal influence on CD44 function. These findings indicate that O-linked glycosylation may be as important as alternative splicing in the regulation of CD44 function and the broad spectrum of biological processes attributed to it, including normal development, tumor metastases, and lymphocyte function.

Alternative Splicing↗
PubMed1996

Keratan sulfate modification of CD44 modulates adhesion to hyaluronate.

CD44 alternative splicing has been implicated in the regulation of CD44 function. CD44 undergoes significant posttranslational modification in all cells, but the functional consequences of these modifications are poorly understood. In the current study, we have demonstrated that keratan sulfate modification of CD44 significantly modulates its ability to bind to hyaluronate. We observed naturally occurring differences in CD44 keratan sulfate substitution between two clonal variants of the KM12 human colon carcinoma cell line. CD44 on the highly metastatic KM12L4 clone is more heavily substituted with keratan sulfate than CD44 on the poorly metastatic KM12C6 clone. Moreover, CD44H on KM12L4 bound to hyaluronate poorly compared to CD44H on KM12C6. Removal of keratan sulfate from CD44 greatly enhanced CD44-mediated cell adhesion to hyaluronate. Removal of keratan sulfate from CD44H-immunoglobulin fusion proteins also enhanced their adhesion to hyaluronate. The influence of glycosaminoglycan substitution on CD44 function was specific to keratan sulfate substitution; treatment to remove chondroitin sulfate, heparan sulfate, or hyaluronate did not affect CD44-mediated cell adhesion to hyaluronate. Use of site-directed CD44H cDNA mutants with arginine changed to alanine at position 41 indicated that keratan sulfate modification of CD44 modulates hyaluronate adhesion through its B loop domain. These findings suggest that keratan sulfate modification of CD44 may play an important regulatory role in the broad spectrum of biological processes attributed to CD44, including normal development, tumor progression, and lymphocyte function.

Alternative Splicing↗
PubMed1995

CD44 hyaluronate binding influences growth kinetics and tumorigenicity of human colon carcinomas.

CD44 is a cell surface receptor of hyaluronate that is implicated in the regulation of tumor growth and metastatic potential. Transformation of colon mucosa to carcinoma is associated with overexpression of several CD44 alternative splice variants. The functional roles of CD44 isoforms in colon carcinoma tumor progression remain unclear. CD44H expression is downregulated in colon carcinomas compared to paired normal mucosa. In the present study we demonstrate that reintroduction of CD44H back into colon carcinoma cells by stable transfection reduces their in vitro growth rate and tumorigenicity. Examination of several colon carcinoma cell lines and use of mutant CD44H reveal that this in vitro and in vivo growth reduction requires the ability of CD44H to bind hyaluronate. These observations indicate that the CD44H downregulation associated with transformation of mucosa to colon carcinoma may provide the carcinoma cells with a growth advantage. Furthermore, the reduction in tumor growth rate mediated by reintroduction of CD44H into colon carcinoma cells is dependent on its ability to bind hyaluronate.

Animals↗
PubMed1995

Restoration of CD44H expression in colon carcinomas reduces tumorigenicity.

OBJECTIVE: The functional consequences of reintroduction of the CD44H cell adhesion molecule into colon carcinomas were investigated. BACKGROUND: CD44 is a cell surface adhesion molecule that is normally present in numerous isoforms as a result of messenger RNA alternative splicing. Individual CD44 isoforms differ in their ability to enhance tumorigenic or metastatic potential when overexpressed on tumor cells. Reverse transcriptase-polymerase chain reaction analysis demonstrates that CD44H is down-regulated during transformation of normal colon mucosa to carcinoma. The functional consequences of CD44H down-regulation in colon carcinomas has not been clarified. METHODS: Tumor cell lines and fresh tissue specimens were examined for CD44 expression by Western blot analysis. CD44H cDNA and site-directed mutants of CD44H cDNA were transfected into colon carcinoma cells. Stable transfectants were examined for adhesion to hyaluronate, in vitro growth, and in vivo growth. RESULTS: CD44H expression was nearly undetectable in primary colon carcinomas and colon carcinoma cell lines. In contrast, normal mucosa expressed high levels of CD44H. When CD44H was reintroduced into colon carcinoma cells, their in vitro and in vivo growth was significantly reduced. This CD44H-mediated growth rate reduction required an intact cytoplasmic domain. CONCLUSIONS: Transformation of normal mucosa to colon carcinoma is associated with a down-regulation of CD44H, which consequently may enhance the growth rate and tumorigenicity.

Blotting, Western↗
PubMed1995

Psychological adjustment of children evaluated for short stature: a preliminary report.

Since synthetic growth hormone became available in the mid-1980s, there has been debate about its use for non-growth-hormone-deficient short children. Justification for this use of growth hormone often is based on a presumed association of short stature with significant psychosocial maladjustment. However, systematic evaluation of psychosocial functioning in short children has been limited, and our understanding of this area is scant. In this study, we have used a combination of interview and self-report measures to examine self-esteem, personality characteristics, affective functioning, coping style, and stature-related stresses in 41 children (5 to 16 years) referred to a pediatric endocrinology service because of short stature. Parent-report and child measures of self-esteem and psychological functioning indicated no evidence of maladjustment in comparison with norms. Furthermore, within the subject sample, the degree of short stature was not related to poor psychological functioning. We found limited evidence linking increased age with increased distress, suggesting that short stature may pose greater difficulties for children as they enter adolescence. Taken as a whole, however, the results do not support the contention that short stature is generally associated with psychosocial maladjustment in children referred for evaluation of their short stature.

Adaptation, Psychological↗
PubMed1995

Effects of oral creatine loading on single and repeated maximal short sprints.

This investigation determined whether oral creatine (Cr) loading could enhance single and repeated short sprint performance. A 1 x 10 s cycle sprint (Study One) and 6 x 6 s (departing every 30 s) repeated cycle sprints (Study two) were the performance tests used. Separate groups of subjects, randomly assigned to either a Cr or placebo (P) group, were used in each study in a double blind design. After performing a familiarization and two baseline tests subjects loaded with 5g of Cr or P four times per day for five days before repeating the tests one and three days post-loading. In Study One (n = 9 in each group), work completed (kJ) at 2, 4, 6, 8 and 10 s and peak power (W) were greater than baseline values in each of the post-loading trials in both the Cr and P groups. There were no between group performance differences. In Study Two (n = 11 in each group) after loading, the Cr group recorded significantly greater scores than the P group in total work (kJ) completed over the 6 sprints, work completed in sprint 1, and peak power (W). Post-exercise blood lactate and pH responses were not different between the Cr and P groups after loading in either study. Although Study One results are equivocal, Study Two results suggest that Cr supplementation can enhance both single (if sprint 1 results are considered in isolation) and repeated short sprint performance.

Administration, Oral↗
PubMed1994

Haem precursor effects on [3H]-PK 11195 binding to platelets.

The haem precursors delta-aminolaevulinic acid (ALA) and porphobilinogen (PBG), over-produced in acute intermittent porphyria (AIP), may mediate porphyric neuropathy. Porphyrins bind to peripheral benzodiazepine receptors, putative mitochondrial porphyrin translocation sites. In AIP, ALA and PBG may interfere with porphyrin transport causing a deficit in essential haemoproteins. The effects of ALA, PBG and protoporphyrin 1X on the binding of [3H]-PK 11195 to platelets were examined. Ligand binding was also examined in platelets from porphyric patients. The haem precursor protoporphyrin 1X (10 microM) caused an increase in Kd values (p < 0.05) whereas Bmax values remained unaltered. Neither ALA (10 microM) nor PBG (10 microM) altered ligand binding. Patient platelets showed no change in ligand binding values. ALA and PBG are unlikely to compete with porphyrins for peripheral benzodiazepine sites.

Aminolevulinic Acid↗
PubMed1994

Developmental expression of poly(A) binding protein mRNAs during spermatogenesis in the mouse.

The poly(A) binding protein (PABP), a conserved protein that binds to the 3' poly(A) tail on mRNAs in eukaryotic cells, has been implicated in the regulation of mRNA stability and translation. Two PABP cDNAs with different sequences were isolated from mouse testis cDNA libraries. The predicted amino acid sequence of one, PABP1, is nearly identical (98.9%) to human liver PABP, while 80% of the amino acids of the second, PABPt, are identical to mouse and human PABPs. Northern blots reveal that there is one major PABP mRNA species in liver, muscle, kidney, and brain, two in spleen, and at least four in testis. The levels of PABP mRNA in testis are 5-10-fold higher than in these somatic tissues, but surprisingly the vast majority of all PABP mRNA size variants sediment more slowly than single ribosomes, indicating strong translational repression. Reverse transcriptase-polymerase chain reaction assays demonstrate that PABPt mRNAs are abundant only in testis. Northern blots of RNAs purified from highly enriched spermatogenic cells show that the high levels, multiple sizes of PABP mRNAs, and the PABPt mRNA are present in meiotic and early haploid spermatogenic cells, and are sharply reduced in late haploid cells. Comparison of the binding of PABP1 and PABPt to poly(A) Sepharose in vitro revealed subtle differences, even though PABPt contains substitutions for highly conserved aromatic amino acids that are thought to be necessary for binding to poly(A). The existence of two PABP isoforms in mouse spermatogenic cells could influence cytoplasmic gene expression during spermatogenesis.

Amino Acid Sequence↗
PubMed1994

Prevalence of hypertension in rural west Africa.

The prevalence of hypertension in rural African communities has been reported previously to be relatively low, with prevalence rates ranging between 2.5% and 10.9%. The authors obtained blood pressure recordings in 3,588 adult residents (age > 20 years) of the Liberian Agricultural Company rubber plantation, located in rural Liberia, West Africa. Blood pressures were obtained using automated digital blood pressure machines in a house-to-house survey. Individuals with a systolic blood pressure greater than 139 mm Hg or a diastolic blood pressure greater than 89 mm Hg were referred to a central site, where three subsequent blood pressure determinations were made, the mean of which was used to determine whether people were hypertensive. The overall prevalence of hypertension (blood pressure > 139/89 mm Hg) was 12.5%. Hypertension was most common in the older women (prevalence 5.7% in women age 20-24 years old, 50% in women older than 55). Using more stringent criteria for hypertension, systolic blood pressure greater than 159 mm Hg or diastolic blood pressure greater than 94 mm Hg, 20% of women between 50-54 had hypertension and 26% of the women older than 55 had hypertension. In some ethnic groups, the prevalence of hypertension was as high as 25%. Based on these results, the prevalence of hypertension in some rural African communities may be higher than reported previously, particularly in older women and among certain ethnic groups, possibly suggesting a strong hereditary component.

Adult↗
PubMed1992

Sequence of the gene encoding the mitochondrial capsule selenoprotein of mouse sperm: identification of three in-phase TGA selenocysteine codons.

The mitochondrial selenoprotein is a major structural protein of the keratinous mitochondrial capsule in mammalian sperm, a structure that functions in shaping mitochondria into the helical sheath surrounding the flagellum. A cDNA clone (Kleene et al., 1990) was isolated previously encoding a protein whose predicted size and amino acid content of > 20% cysteine and proline closely resembled a selenoprotein in the bull mitochondrial capsule. The sequences of additional cDNAs and genomic DNA reported here reveal that the mouse mitochondrial capsule selenoprotein reading frame begins 54 codons further upstream than previously reported. Significantly, these 54 codons contain three in-phase UGA codons, which normally signify stop but encode selenocysteine in bacterial and mammalian selenoproteins. The coding region of the mitochondrial capsule selenoprotein gene is interrupted by a single intron. S1 mapping and primer extension demonstrate that the vast majority of MCS mRNAs are spliced using consensus 5' and 3' slice junctions in mammalian cells. However, two cDNAs have been identified that apparently represent rare mRNA variants produced by use of cryptic splice sites.

Amino Acid Sequence↗