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Biomedical subjects

R Clark

Publications and source records attributed to R Clark.

At least 91 records · Page 5Linked to original sources
PubMed1998

Pregnancy is not associated with the progression of HIV disease in women attending an HIV outpatient program.

The objective of this study was to determine whether pregnancy is associated with an acceleration of human immunodeficiency virus (HIV) disease progression in women who have a pregnancy while HIV infected. A retrospective review of all women aged 15-35 years who attended an HIV outpatient program from January 1989 through August 1995, was undertaken. The 192 women who had a term pregnancy after testing positive for HIV were compared with 164 women who were not pregnant during the same period. The main outcome measures were death, the occurrence of a first acquired immunodeficiency syndrome (AIDS)-defining condition, or a condition indicative of symptomatic HIV. Disease progression was assessed using the Kaplan-Meier method and multivariate proportional hazards models. Compared with nonpregnant women, women with a term pregnancy were significantly more likely to be African-American (88% vs. 78%, p < 0.05), younger than 22 years of age (51 % vs. 11%, p < 0.001), and to have entered the clinic with a higher median CD4 count (519 vs. 433 cells/microl, p < 0.001). After adjusting for entry CD4 count and other factors, pregnancy was not associated with progression to any of the study outcomes. Thus, in women attending a publicly funded clinic, pregnancy does not appear to accelerate the progression of HIV disease.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Differential diagnosis of gammopathies by capillary electrophoresis and immunosubtraction: analysis of serum samples problematic by agarose gel electrophoresis.

The capabilities of capillary electrophoresis (CE) for serum protein electrophoresis and immunotyping have been demonstrated. CE-based systems specifically designed for serum protein electrophoresis and immunotyping via immunosubtraction (IS) are now available and are being evaluated for efficiency, specificity and sensitivity by several groups. The use of CE for serum protein electrophoresis and immunotyping (IS) in the clinical laboratory compares well with agarose gel electrophoresis (AGE) and immunofixation (IF) for the detection and characterization of monoclonal proteins. In addition to routine use, this technology is useful for a subset of serum samples that are difficult to interpret with conventional technology. In this study, sera abnormalities difficult to detect/interpret by AGE-IF are subdivided into four categories: (i) patients with polyclonal increases in immunoglobulin, (ii) point of application artifacts, (iii) abnormalities in the beta region, and (iv) patients with free light chains. CE is superior to AGE for evaluating samples characterized by the above abnormalities. Sera containing monoclonal proteins within a polyclonal increase are easier to detect by CE as well as being easier to type by IS than by IF. Point-of-application artifacts, periodically observed with AGE, do not exist on CE since the point of detection is remote from the point of application. Enhanced resolution in the beta region allows for increased detection of monoclonal proteins migrating in this region. Some free light chains are undetected by CE as a result of no apparent abnormalities on the CE serum protein profile and, thus, still require IF for detection. CE detects more serum electrophoretic abnormalities than AGE in this clinically important group of patients with Bence Jones proteinemia.

Antibodies, Monoclonal↗
PubMed1998

Regulation of B and T cell development by anterior pituitary hormones.

Hormones produced by the anterior pituitary gland have been implicated in the regulation of primary lymphocyte development. In order to identify endocrine factors involved in that process, several strains of mice with genetic defects resulting in a selective impairment in the production of one or more anterior pituitary-derived hormones have been analysed. This study has resulted in the classification of endocrine hormones into the following four categories: (i) hormones such as prolactin with no apparent effects on primary lymphopoiesis; (ii) anabolic hormones such as growth hormone and insulin-like growth factor-I whose stimulatory effects on primary lymphopoiesis are non-lineage-specific and related to their actions as systemic mediators of growth and/or differentiation; (iii) hormones such as thyroid hormones that have an obligate role in primary B lymphopoiesis; and (iv) hormones such as oestrogens that act as negative regulators of lymphopoiesis.

Animals↗
PubMed1998

Involvement of MAP kinase in the cyclic AMP induction of myelin basic protein gene expression.

Cyclic AMP is involved in the differentiation of oligodendrocyte and Schwann cell progenitors into mature myelin producing cells. The involvement of MAP kinases in this pathway was investigated in the D6P2T cell line. This cell line can be induced to display a differentiated phenotype characterized by myelin basic protein gene expression by increased cyclic AMP. Blocking MAP kinase activity with inhibitors of the activating kinase, MEK, by expression of a dominant negative MAP kinase or by expression of the MAP kinase inactivating phosphatase Mkp-1 all blocked the activation of the myelin basic protein promoter in D6P2T cells. In addition, blocking MAP kinase activation during differentiation of an oligodendrocyte-like cell line, CG4, also leads to inhibition of MBP expression. These findings suggest a role for MAP kinase in the cyclic AMP stimulated expression of the myelin basic protein gene during differentiation.

Calcium-Calmodulin-Dependent Protein Kinases↗
PubMed1998

Cross-pin femoral fixation: a new technique for hamstring anterior cruciate ligament reconstruction of the knee.

A new method of femoral fixation for arthroscopic anterior cruciate ligament (ACL) reconstruction using semitendinosus and gracilis (ST/G) tendons is presented. Biomechanical evaluation of the method was performed with pullout tests using animal tissues simulating fixation of ST/G tendons passing around a 2.5-mm pin placed transversely through a femoral tunnel. Clinical assessment of 22 patients was performed according to IKDC, Tegner, Lysholm, isokinetic strength, and KT1000 standards. Fixation strengths ranged from 725 N to 1,600 N for yield and maximal loads to failure for 35-mm to 70-mm cross-pins. Clinical results at mean follow-up of 30 months showed one traumatic failure, IKDC 86% normal or nearly normal, Tegner 6 ave, Lysholm 93 ave, KT1000 86% < 3 mm side-to-side difference on maximal manual evaluation, and isokinetic strength testing of quadriceps 8% deficit with hamstrings 8% deficit. Cross-pin fixation of ST/G tendons may be one of the strongest modes of femoral graft attachment yet devised. Our clinical outcomes in this initial series compare well with previous reports of ACL reconstruction regardless of graft or technique.

Adolescent↗
PubMed1998

Ten novel 11q23 chromosomal partner sites. European 11q23 Workshop participants.

The MLL gene located at 11q23 has been described as a 'promiscuous' gene due its involvement with a large number of genetic partners. The EU Concerted Action Workshop on 11q23 provided 550 cases for study of which 82 showed abnormalities which did not involve the established translocations or deletion of 11q23. In these 'other' cases, which included inversions and duplications, 11q23 was found to be involved with 25 chromosome partners of which 10 had not been previously reported. These were 1q31, 4p11, 6q13, 8q21, 10q22, 10q25, 11q11, 11q21, 13q34 and 18q23. This study demonstrated the value of the Workshop, in confirming the diversity of chromosomal partner sites involved with 11q23 and in the identification of new partners.

Acute Disease↗
PubMed1998

Abnormalities of the ETV6 gene occur in the majority of patients with aberrations of the short arm of chromosome 12: a combined PCR and Southern blotting analysis.

Involvement of the ETV6 gene, located at 12p13, has been investigated in 20 patients with an abnormality of the short arm of chromosome 12 (abn 12p) detected cytogenetically. Patients in the study had c/pre-B acute lymphoblastic leukemia (ALL) (nine children and three adults), T-ALL (three adults), acute myeloid leukemia (AML) (two adults), biphenotypic acute leukemia (Bip-L) (one adult), myelodysplasia (MDS) (one adult) and chronic myelomonocytic leukemia (CMML) (one child). Abnormalities of 12p comprised deleted (del)(12p) alone (seven cases), add(12p) alone (seven cases), del(12p) and add(12p) (one case) and balanced translocations of 12p to 1p13, 1q31, 10q11, 14q11 and 15q15 (one case of each). A novel, exon-specific RT-PCR assay identified breakpoints in ETV6 in nine of 19 cases, and showed breakpoints in intron 5 (seven cases of children with c-ALL), in intron 4 (in one adult with Bip-L) and in intron 2 (in one adult with AML). RT-PCR for the ETV6/AMLI fusion (tested in 19 cases) was positive using standard primers in five cases (four of which had shown rearrangements in intron 5) and occurred as a variant fusion in a sixth case (also positive for a rearrangement in intron 5) using 3' RACE PCR. Southern blotting confirmed rearrangements in intron 5 in the five cases available for analysis and revealed a rearrangement in intron 5 in one of 10 cases with no evidence of intron 5 involvement by RT-PCR. Rearrangements in intron 5 of ETV6 were found in eight of nine cases of children with c-ALL of which six carried the ETV6/AMLI fusion. Heterozygosity within intron 5 (revealed by the genomic probe B1) was found in seven of 11 cases tested. Deletion of one allele was indicated in three cases with del(12p) and one case with add(12p). This study, using a combination of ETV6 exon-specific RT-PCR, RT-PCR for ETV6/AMLI and Southern blotting has shown that rearrangement and/or deletion of ETV6 may occur in up to 70% of patients with abn 12p. Furthermore, 90% of children in this study with an abn 12p and c-ALL, carried a rearrangement of ETV6 in intron 5.

Adolescent↗
PubMed1998

Isolation of parvalbumin isotypes by preparative HPLC techniques.

Parvalbumins are highly stable Ca2+ binding proteins, present in large quantities in the sarcoplasmic reticulum in the white muscle of most lower vertebrates and fish. The properties of these proteins make them promising antigens for the use as a specific biomarker for fish species identification. Parvalbumin isotypes were isolated, on a preparative scale level, by use of size exclusion chromatography (SEC) and anion exchange HPLC. The utility of this technique, with regard to maximizing purified isotypes, is discussed.

Animals↗
PubMed1998

Prospective study of serum protein capillary zone electrophoresis and immunotyping of monoclonal proteins by immunosubtraction.

Capillary zone electrophoresis and immune adsorption were evaluated for identification of serum protein abnormalities and immunotyping of monoclonal proteins. A 7-capillary, electrophoresis instrument and solid phase immunosubtraction reagents were used in a prospective study of 1,518 patients. Serum protein electrophoresis was performed by agarose gel electrophoresis and capillary electrophoresis and interpreted with regard to identification of abnormalities consistent with monoclonal gammopathies. The agarose gel electrophoresis had a sensitivity and specificity of 91% and 99%, respectively, whereas capillary electrophoresis gave results of 95% and 99%. Immunotyping of the monoclonal proteins was performed by immunofixation and immunosubtraction. Capillary electrophoresis was more sensitive than agarose gel electrophoresis for the identification of monoclonal proteins in serum. In addition, the immunosubtraction method seems technically simpler and more automated than immunofixation and represents a useful additional approach for immunotyping monoclonal proteins.

Antibodies, Monoclonal↗
PubMed1998

Disturbances of growth hormone-insulin-like growth factor axis and response to growth hormone in acidosis.

Severe chronic metabolic acidosis (CMA) in rats is associated with poor food intake and downregulation of growth hormone (GH), insulin-like growth factors (IGFs), and liver receptors; the administration of recombinant GH (rGH) fails to improve the growth failure. In mice with carbonic anhydrase II deficiency (CAD), a model of moderate CMA with food intake close to normal, we studied serum levels of GH, IGFs, and IGF-binding proteins, and the growth response to rGH. CAD was associated with low serum levels of GH in males. Randomized administration of rGH from approximately 5 to approximately 12 wk to CAD mice improved food efficiency and increased serum IGF-I levels, final length, and weight compared with placebo without affecting blood pH. Although administration of rGH also increased linear growth in healthy animals, the effect was less than that in CAD mice and was only observed when started before 6 wk of life. Thus growth failure in CAD mice is associated with a decrease in GH secretion in males but not in females. Long-term administration of rGH increases linear growth in CAD mice despite persistent CMA.

Acidosis↗
PubMed1998

Effects of insulin-like growth factor administration and bone marrow transplantation on thymopoiesis in aged mice.

There has been considerable interest in using hormone replacement therapy to rejuvenate the involuted thymus during aging. GH and insulin-like growth factor-I (IGF-I), a mediator of GH actions, have been of particular interest because of their thymopoietic effects and the fact that their serum concentrations decline during aging. However, treatment of aging rodents with either GH or IGF-I does not restore thymus cellularity to levels present in young animals, suggesting that additional defects might limit the magnitude of their effects. In particular, deficiencies have been reported to accumulate in the bone marrow T cell precursor compartment during aging. In view of this, 18-month-old mice were administered either recombinant IGF-I, bone marrow cells from young mice, or a combination of IGF-I and young bone marrow cells. Thymus cellularity in the latter group of mice was significantly higher than in animals treated with hormone or bone marrow transplantation alone, suggesting that optimal therapies for restoring thymus cellularity must address both endocrine and hematopoietic defects that accumulate during aging. Results from in vitro studies using fetal thymic organ cultures suggest that IGF-I acts by potentiating thymic colonization by bone marrow T cell precursors and/or that the hormone affects some other event soon after thymus colonization.

Aging↗
PubMed1998

Cloning of two novel growth hormone transcripts expressed in human placenta.

Several isoforms of human GH (hGH) are produced by two related genes expressed in the pituitary (hGH-N) and in the placenta (hGH-V). These genes consist of five exons (denoted 1-5) separated by four introns (denoted A-D). In the present report, two new transcripts of the hGH-V gene are described. The coding region of the hGH-V gene was amplified by RT-PCR using placental complementary DNA as template. DNA sequencing of several clones revealed two novel transcripts. One had a 45-bp deletion caused by the use of an alternative splice acceptor site within exon 3, similar to that in the hGH-N gene, predicting a 20-kDa isoform of hGH-V. The other transcript was generated by the use of an alternative splice donor site causing a 4-bp deletion in the end of exon 4, predicting a 24-kDa protein with 219 amino acids, which we refer to as hGH-V3. The carboxy-terminal sequence of hGH-V3 differs from 22-kDa hGH-V and hGH-V2, the two previously reported transcripts of the hGH-V gene, and does not contain a predicted transmembrane domain as described for hGH-V2. Ligase chain reaction was then used to analyze the possible use of the same splicing pattern in transcripts derived from the other genes of the hGH-gene cluster. Alternatively spliced transcripts encoding the 20-kDa hGH isoform were detected from the hGH-N and hGH-V genes, but not from the human chorionic somatomammotropin-A/B genes. The alternative splicing generating hGH-V3 was only demonstrated in transcripts derived from the hGH-V gene. Using competitive RT-PCR, the expression of hGH-V3 was estimated to be 10% of the hGH-V messenger RNA in full-term normal placentas and in placentas from pathological pregnancies. The 20-kDa hGH-V was detected in two of four full-term normal placentas, whereas a weak signal was observed in one of the pathological placentas. We conclude that the hGH-V primary transcript undergoes alternative splicing pathways generating at least four different messenger RNAs, predicting the expression of different hGH isoforms, including two with a complete sequence divergence in the carboxy-terminus.

Alternative Splicing↗
PubMed1998

A cross-national test of propositions from the neo-pluralist perspective on Social Security expenditures.

Much of the existing literature on cross-national differences in retirement wage policy has focused on the inception of programs and the factors leading to their introduction. The explanations may be less adequate in accounting for post-war changes in social security programs. To interpret the evolution of programs in the post-war period, we stress the importance of divisions among workers themselves. We argue here that such divisions may occur along three fault lines: (1) ethnic, racial, and linguistic differentiation (2) the split between heavily urbanized and other segments of the working population and (3) fractionalization brought about by domination of a single industry. Using a longitudinal design to measure changes in social security expenditures in 34 nations between 1965 and 1983, we test hypotheses asserting that fragmentation among workers is inversely correlated with expanded investment in benefits for workers. We find general support for these hypotheses.

Aged↗
PubMed1998

Stachybotrys, a mycotoxin-producing fungus of increasing toxicologic importance.

BACKGROUND: Stachybotrys as a fungus has been implicated as a source of mycotoxins. While the toxicity of several well-known mycotoxins (aflatoxins) is well documented, recent studies on Stachybotrys have raised the question that mycotoxins produced by this fungus may be responsible for the health effects of occupants in water-damaged buildings. METHODS: Published articles regarding Stachybotrys-related mycotoxins were reviewed with particular focus on human toxicity. RESULTS: A critical review of papers, reports, and studies on Stachybotrys mycotoxins revealed only descriptive reports of suspected animal and human poisoning secondary to consumption of mold-contaminated food products. No studies of good toxicologic and epidemiologic designs answer whether airborne mycotoxins produced by Stachybotrys could produce specific human toxicity. CONCLUSIONS: Current data on the toxicology of mycotoxins produced by Stachybotrys demonstrate that this group of mycotoxins is capable of producing immunosuppression and inflammatory insults to gastrointestinal and pulmonary systems. Case control study and case reports have suggested a possible association with environmental exposure to Stachybotrys mycotoxins, although a firm causal relationship has not been firmly established. Additional studies are needed to document that humans with sufficient exposure to these mycotoxins develop compatible clinical and pathologic pictures as demonstrated in animal models.

Animals↗
PubMed1998

Small-cell lung cancer: treatment progress and prospects.

Although small-cell lung cancer (SCLC) represents only 20% of all lung cancer cases in the United States, it is the most lethal subtype. Combination chemotherapy unequivocally offers the best chance for improved survival in SCLC. Either PE (platinum plus etoposide) or CAV (cyclophosphamide, Adriamycin, and vincristine) is a reasonable first-line therapy. Alternating PE with CAV does not appear to be significantly superior to PE or CAV alone. Increasing dose intensity, although sometimes associated with higher response rates, does not appear to significantly improve survival and should not be used outside of a clinical study. Several new agents with novel mechanisms of action show promise in treating SCLC. These include: gemcitabine (Gemzar), paclitaxel (Taxol), docetaxel (Taxotere), topotecan (Hycamtin), and irinotecan (Camptosar). Given the poor survival and response rates in relapsed patients and the chemoresponsiveness of SCLC, patients with newly diagnosed extensive disease should be encouraged to enroll in phase I or II trials. Thoracic radiotherapy confers a small survival advantage in limited-stage SCLC patients. Although prophylactic cranial irradiation does not significantly improve survival, it does reduce central nervous system (CNS) recurrences with minimal long-term sequelae. Surgery should be considered only for: (1) resection of a solitary pulmonary nodule, which must be followed by adjuvant chemotherapy; and (2) resection of an unresponsive chest tumor, which may harbor a non-small-cell lung cancer component.

Antineoplastic Agents↗