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Biomedical subjects

S Ackerman

Publications and source records attributed to S Ackerman.

At least 19 recordsLinked to original sources
PubMed2000

Generativity in midlife and young adults: links to agency, communion and subjective well-being.

Three questions stimulated by Erik Erikson's theory of generativity were addressed: 1) Is generativity associated with greater subjective well-being? 2) Are agency and communion additive or interactive predictors of generativity? 3) Does generativity play a distinct role during the midlife period? Among ninety-eight midlife adults, generativity was positively related to positive affectivity, satisfaction with life, and work satisfaction. Generativity was independently predicted by agentic (masculine) and communal (feminine) traits. Among fifty-eight young adults, generativity predicted positive affect at home. Generativity was independently predicted by agentic (power) and communal (love) interpersonal orientations. Using event-contingent recording of agentic and communal behavior at work, agency was a stronger predictor of generativity for young adult men, and communion was a stronger predictor for young adult women. The studies demonstrate that generativity has similar relations to agency and communion in young and midlife adults; however, generativity may be a stronger predictor of subjective well-being in midlife adults.

Adaptation, Psychological↗
PubMed1999

Oral immunization with urease and Escherichia coli heat-labile enterotoxin is safe and immunogenic in Helicobacter pylori-infected adults.

BACKGROUND & AIMS: Oral immunization with Helicobacter pylori urease can cure Helicobacter infection in animals. As a step toward therapeutic immunization in humans, the safety and immunogenicity of oral immunization with recombinant H. pylori urease were tested in H. pylori-infected adults. METHODS: Twenty-six H. pylori-infected volunteers were randomized in a double-blind study to four weekly oral doses of 180, 60, or 20 mg of urease with 5 microg heat-labile enterotoxin of Escherichia coli (LT), LT alone, or placebo. Side effects and immune responses were evaluated weekly after immunization, and gastric biopsy specimens were obtained after 1 month and 6 months for histology and quantitative cultures. RESULTS: Diarrhea was noted in 16 of 24 (66%) of the volunteers who completed the study. Antiurease serum immunoglobulin A titers increased 1. 58-fold +/- 0.37-fold and 3.66-fold +/- 1.5-fold (mean +/- SEM) after immunization with 60 and 180 mg urease, respectively, whereas no change occurred in the placebo +/- LT groups (P = 0.005). Circulating antiurease immunoglobulin A-producing cells increased in volunteers exposed to urease compared with placebo (38.9 +/- 13. 6/10(6) vs. 5.4 +/- 3.1; P = 0.018). Eradication of H. pylori infection was not observed, but urease immunization induced a significant decrease in gastric H. pylori density. CONCLUSIONS: H. pylori urease with LT is well tolerated and immunogenic in H. pylori-infected individuals. An improved vaccine formulation may induce curative immunity.

Administration, Oral↗
PubMed1999

Treatment outcomes for female octogenarians with breast cancer.

Scant information is available comparing the treatment outcomes of minor surgery (lumpectomy) versus extensive treatment (radical and simple mastectomy or lumpectomy and radiation) in octogenarians with breast cancer. Medical records of women (ages 80-89) who received treatment for breast cancer from 1984 through 1994 were reviewed. All patients were stage T1 or T2, and none had palpable lymph nodes. The recurrence rate, disease-free interval, and death rate for both groups were compared. Of the 41 patients representing 43 minor surgeries, 12 per cent (5 of 41) of patients developed recurrence, all of which were related to the primary breast tumor. The mean disease-free interval was 28.6 +/- 24.7 months (range, 6-65). Forty-six per cent (18 of 39) of patients died, 10 per cent (4 of 39) from recurrence and metastatic disease from breast cancer and 36 per cent (14 of 39) from other causes. Of those who underwent extensive treatment, 14.6 per cent (7 of 48) of patients experienced recurrence, all related to the primary breast tumor. The mean disease-free interval was 24.0 +/- 21.9 months (range, 2-71). Forty-eight per cent (23 of 48) of patients died, 10 per cent (5 of 48) from recurrence and metastatic disease from breast cancer and 37 per cent (18 of 48) from other causes. None of the differences between the minor surgery versus extensive treatment groups were statistically significant. The recurrence rate, disease-free interval, and death rate from recurrent disease are similar for patients undergoing minor surgery compared with those undergoing extensive treatment.

Aged↗
PubMed1997

Coactivators and TAFs of transcription activation in wheat.

Transcription regulation often activates quiescent genes in a tissue-specific or developmental manner. Activator proteins bind to a DNA sequence upstream of the promoter, interact with the general transcription proteins via bridging proteins, and elevate transcription levels. One group of bridging proteins, the coactivators, have been characterized in animals as polypeptides tightly associated with the general transcription factor TATA-binding protein (TBP). They are referred to as TAFs (TBP-associated factors), and together with TBP comprise general transcription factor IID. We provide biochemical evidence that wheat IID contains coactivators. An activator protein with an acidic activation domain facilitates the binding of IID to the template, and potentiates activated in vitro transcription with wheat IID, but not with wheat TBP. Using antibodies to wheat TBP, we demonstrate that wheat IID also contains TAFs. This is the first demonstration that a plant contains coactivators and TAFs.

Animals↗
PubMed1997

Dual diagnosis subtypes in urban substance abuse and mental health clinics.

OBJECTIVES: This study sought to determine rates of dual disorders (psychiatric and substance use disorders) in a population of low-income inner-city outpatients, to compare the rates in outpatient mental health and substance abuse treatment settings, and to examine the clinical usefulness of classifying patients with dual disorders into three subtypes. METHODS: A total of 57 low-income urban residents receiving mental health treatment and 73 receiving substance abuse treatment were given semistructured clinical interviews to ascertain lifetime and concurrent DSM-III-R axis I disorders. Patients with dual disorders were classified into subtypes depending on whether their psychiatric or substance use disorder was caused by the comorbid disorder or whether both disorders existed independently. RESULTS: Eighty-three patients had a lifetime history of dual disorders: 34 patients (60 percent) in the mental health settings and 49 (67 percent) in substance abuse treatment. Among the 83 with dual disorders, more than half had experienced symptoms of both disorders within the past year. Each of the disorders was considered primary (that is, no indication was found that one was caused by the other) for 24 patients in the mental health settings (71 percent) and 31 in the substance abuse treatment settings (63 percent). CONCLUSIONS: In each type of treatment setting, nearly two-thirds of the patients met criteria for a lifetime diagnosis of a dual disorder. This high rate of comorbidity did not appear to be attributable to substance use causing psychiatric symptoms, or vice versa. The high rate suggests the need for greater integration of mental health and substance abuse treatment, regardless of setting.

Adult↗
PubMed1996

Rheumatoid factor idiotypic and antigenic specificity is strongly influenced by the light chain VJ junction.

The aim of this study was to define the structural basis for rheumatoid factor (RF) specificity and for the expression of the RF light chain-associated Ids, 4C9 and 6B6.6, by determining the reactivity of recombined heavy and light chains of Ig derived from monoclonal B cell lines of patients with rheumatoid arthritis and of light chains with site-directed mutations. We found that expression of the 4C9 and 6B6.6 Ids resulted from use of the VkIIIa genes Humkv 328 and Vg, but only in the presence of a permissive VJ junction. Expression of the Ids was independent of heavy chain use for the Humkv328-encoded light chains, but was highly dependent on the associated heavy chain for the Vg-encoded light chains. The RF specificity of the Abs was primarily heavy chain dependent, but the light chain VJ junction was critical in determining the relative avidity of the Abs for Fc. Our study points to the critical contribution of the somatically generated VJ junction to RF autoantibody specificity and to the expression of the two RF-associated Ids studied.

Amino Acid Sequence↗
PubMed1995

Postprandial sleep in healthy men.

Twenty-one healthy men between 18 and 30 years of age were studied to determine the effects of midday food intake on sleep. Twelve subjects were administered liquid carbohydrate meals at lunchtime on 2 consecutive days. Subjects slept on 22 of the 24 study days for an average of 93 minutes during 3 hours of postprandial polysomnographic recording. Nine subjects were used as controls and were deprived of a lunch meal. Six of the nine subjects slept for an average of 30 minutes during the postprandial period. This time was significantly shorter than that of subjects in the meal condition (p < 0.005). There was no difference in latency to sleep onset following food intake between the two study groups. The results of this study suggest that lunchtime food intake does not promote the initiation of sleep, but that it does increase the duration of sleep episodes occurring during the postprandial period.

Adolescent↗
PubMed1994

Cloning of the yeast ATP3 gene coding for the gamma-subunit of F1 and characterization of atp3 mutants.

Saccharomyces cerevisiae pet mutants, of complementation group G115, are deficient in mitochondrial ATPase and have properties indicative of defective F1. In this study we show that C287/LU1, a mutant belonging to group G115, is complemented by the yeast nuclear ATP3 gene coding for the gamma-subunit of the mitochondrial F1-ATPase. The amino-terminal sequence of the mature gamma-subunit matches the sequence encoded by ATP3 starting with the 34th amino acid confirming the identity of the gene, and earlier evidence indicating that this F1 component is synthesized as a precursor with a long amino-terminal extension. The properties of the mitochondrial ATPase have been studied in C287/LU1 with an Ala273-->Val substitution in the carboxyl-terminal region of the gamma-subunit and in W303 delta ATP3, a mutant lacking the gamma-subunit as a result of a deletion in ATP3. Both strains have negligible ATPase activity but near normal concentrations of the alpha- and beta-subunits of F1. In W303 delta ATP3, the subunits do not form a stable F1 oligomer nor are they firmly associated with F0. This is not true of C287/LU1, which was found to assemble an F1-F0 complex. These data indicate that the yeast gamma-subunit has dual functions, one in catalysis of ATP hydrolysis/synthesis and the second in assembly/stability of F1.

Amino Acid Sequence↗
PubMed1994

The human DNA polymerase beta gene structure. Evidence of alternative splicing in gene expression.

DNA polymerase beta (beta-pol) is a single-copy gene that is considered to be part of the DNA repair machinery in mammalian cells. Using two human genomic libraries we have cloned the complete human beta-pol gene and determined the organization of the beta-pol coding sequence within the gene. The human beta-pol gene spans 33 kb and contains 14 exons that range from 50 to 233 bp. The 13 introns vary from 96 bp to 6.5 kb. Information derived from this study was used in defining the location of a deletion/insertion type restriction fragment length polymorphism (RFLP) 5' to exon I of the human beta-pol gene. This RFLP was utilized in linkage analysis of DNAs from CEPH families and the results confirm the previous assignment of the human beta-pol gene to chromosome 8 (p12-p11). Analysis of mRNA from six human cell lines using the polymerase chain reaction showed the expression of two beta-pol transcripts. Sequence analysis revealed that the size difference in these transcripts was due to deletion of the 58 bp sequence encoded by exon II, suggesting that the smaller transcript results from an alternative splicing of the exon II sequence during processing of the beta-pol precursor RNA.

Animals↗
PubMed1993

AF64A (ethylcholine mustard aziridinium) impairs acquisition and performance of a spatial, but not a cued water maze task: relation to cholinergic hypofunction.

The cholinergic neurotoxin AF64A (ethylcholine mustard aziridinium) produced alterations in a spatial but not a nonspatial cognitive task following ICV injection. AF64A impaired acquisition and performance in the standard Morris water maze task, evidenced by significantly longer latencies to find the submerged platform. However, the AF64A group exhibited shorter latencies and more direct paths to the target at the end of training, which suggests acquisition of efficient search strategies and a sparing of procedural memory. However, the AF64A group spent significantly less time in the target quadrant during the probe trial than the CSF group. This suggests a failure to learn the specific location of the target and impaired declarative memory processes. In contrast, AF64A did not affect performance of a cued MWM task that did not involve spatial memory processing, demonstrating the absence of motoric, sensory, or motivational impairments. The AF64A-induced behavioral deficits were associated with a) a significant decrease in high affinity choline transport (HAChT), b) reduced concentrations of 5-HT and 5-HIAA, and c) an increased ratio of 5-HIAA/5HT, in the HPC. There were no changes in choline uptake in the gustatory cortex, the amygdala, or the striatum. Percent time in the target quadrant during the probe trial was significantly correlated with HAChT in the HPC. There were no correlations between any of the behavioral measures and HAChT in the striatum, gustatory cortex, or the amygdala, or between serotonergic or noradrenergic parameters in the HPC. These data suggest that AF64A produces cognitive deficits in spatial tasks that are correlated with the cholinergic hypofunction induced by the compound.

Acetylcholine↗
PubMed1993

The effect of psychiatric disorders on weight loss in obesity clinic patients.

Research on psychiatric disorders in obesity has indicated that obese people are not psychiatrically different from nonobese people. Few studies, however, have addressed the potential impact of psychopathology on weight control. In the present study, a consecutive sample of 37 patients presenting to a major metropolitan weight control unit were given structured diagnostic interviews (Structured Clinical Interviews for Diagnosis I and II). These patients completed one of two 12-week diet programs involving either behavior modification or liquid protein diets. After 12 weeks of a liquid protein formula diet, patients with no personality disorder lost significantly more weight than personality disordered patients; personality disordered patients on a behavioral diet tended (p < .15) to lose more weight during a 12-week diet than the patients without personality disorders. These data suggest that there are differential responses to liquid protein and behavioral diets, depending on the presence or absence of a personality disorder.

Adult↗
PubMed1993

Phase I/II study of murine monoclonal antibody-ricin A chain (XOMAZYME-Mel) immunoconjugate plus cyclosporine A in patients with metastatic melanoma.

XOMAZYME-Mel (XMMME-001-RTA) is an immunoconjugate comprised of ricin A chain conjugated to a murine monoclonal antibody directed against high molecular weight melanoma antigens. Although not necessarily related to increased toxicity or decreased efficacy, the development of anti-immunoconjugate antibodies may limit repetitive dosing with an immunoconjugate. We evaluated the role of cyclosporine A in blocking the antibody response in patients with melanoma treated with XMMME-001-RTA. Patients received cyclosporine in divided daily doses to achieve serum levels by HPLC of 150-200 ng/ml on days 1-22. On day 3, XMMME-001-RTA was begun at dosages 0.2-0.6 mg/kg daily for 5 days. Treatment was repeated every 35 days. Three patients were treated in each dosage tier (0.2, 0.4, 0.6 mg/kg). Nine patients were entered and all nine were evaluable. Patients had histologically confirmed melanoma. Metastatic sites included skin, soft tissue, and lymph nodes (seven), lung (two), liver (one), and spleen (one). There were four men and five women aged 46-75 years. Toxicities included myalgia, arthralgia, hypoalbuminemia, fatigue, elevations in liver function tests, and increased peripheral edema. Four patients received two to five repeated dosages of XMMME-001-RTA. One wheal-and-flare reaction from an immunotoxin test dose of XMMME-001-RTA was noted after five cycles. After a test dose subsequent to one cycle, two patients experienced chest tightness without ECG changes and were removed from the study. All toxicities resolved without sequelae. One patient experienced partial lymph node remission for 9 months. A second patient had stable mediastinal disease for 20 months. XMMME-001-RTA is safe when given repeatedly with cyclosporine.

Aged↗
PubMed1992

COQ2 is a candidate for the structural gene encoding para-hydroxybenzoate:polyprenyltransferase.

Coenzyme Q functions as a lipid-soluble electron carrier in eukaryotes. In Saccharomyces cerevisiae, the enzymes responsible for the assembly of the polyisoprenoid side chain and subsequent transfer to para-hydroxybenzoate (PHB) are encoded by the nuclear genes COQ1 and COQ2, respectively. Yeast mutants defective in coenzyme Q biosynthesis are respiratory defective and provide a useful tool to study this non-sterol branch of the isoprenoid biosynthetic pathway. We isolated a 5.5-kilobase genomic DNA fragment that was able to functionally complement a coq2 strain. Additional complementation analyses located the COQ2 gene within a 2.1-kilobase HindIII-BglII restriction fragment. Sequence analyses revealed the presence of a 1,116-base pair open reading frame coding for a predicted protein of 372 amino acids and a molecular mass of 41,001 daltons. The amino acid sequence exhibits a typical amino-terminal mitochondrial leader sequence and six potential membrane-spanning domains. Primer extension and Northern analyses indicate the gene is transcriptionally active. Transformation of a coq2 strain with the 2.1-kilobase HindIII-BglII genomic restriction fragment on a multicopy plasmid restores PHB:polyprenyltransferase activity to wild-type levels. Disruption of the chromosomal COQ2 gene indicates the gene is not essential for viability, yet is required for PHB:polyprenyltransferase activity and respiratory function. In addition, the deduced amino acid sequence of PHB:polyprenyltransferase contains a putative allylic polyprenyl diphosphate-binding site. The presence of this aspartate-rich domain in a number of functionally distinct proteins which utilize polyprenyl diphosphate substrates is reported.

Alkyl and Aryl Transferases↗
PubMed1991

High-resolution 1H NMR imaging of regional ischemia in the isolated perfused rabbit heart at 4.7 T.

High-resolution 1H NMR images of the isolated perfused rabbit heart were recorded before and after the induction of regional ischemia while the heart was arrested. On T2-weighted images the ischemic region appeared darker than the surrounding tissue and a 28% reduction in T2 was measured from the images. Infusion of an NMR contrast agent demonstrated that the hypointense region on the T2-weighted image was from the ischemic region, which was further confirmed by histological analysis of the heart. It is proposed that the decreased T2 in the ischemic region may be a consequence of changes in water compartmentalization. It is possible that these changes may be used to follow the evolution of tissue injury during ischemia, and therefore provide information regarding the transition between reversible to irreversible injury in the isolated perfused heart.

Animals↗
PubMed1991

Genes for collagen types I, IV, and V are transcribed in HeLa cells but a postinitiation block prevents the accumulation of type I mRNA.

Collagen mRNA synthesis in HeLa cells was evaluated by in vitro transcription of type I collagen DNA, nuclear run-on studies, and steady-state mRNA analysis. Type I collagen mRNA was accurately initiated by HeLa cell RNA polymerase II in nuclear extracts, and run-on analysis indicted that mRNAs for collagen types alpha 1(I), alpha 2(I), alpha 1(III), alpha 1(IV), and alpha 2(V) were synthesized in HeLa cells. However, on assessing the steady-state levels of mRNAs of collagen types alpha 1(I), alpha 2(I), alpha 1(IV), and alpha 2(V), no type I mRNA was found in HeLa cells while types alpha 1(IV) and alpha 2(V) collagen mRNAs were observed. These results suggest that a postinitiation process prevents the accumulation of type I collagen mRNAs in HeLa cells. Persistence of types IV and V collagen mRNAs is consistent with the involvement of types IV and V collagen in adhesion of HeLa cells to glass or plastic.

Cell Nucleus↗
PubMed1990

Transcription factor IIA of wheat and human function similarly with plant and animal viral promoters.

Eucaryotic transcription initiation by RNA polymerase II involves protein:DNA interactions during the formation of a transcription complex. In addition to RNA polymerase II there are at least five other general transcription factors necessary for initiation with the adenovirus major late promoter. One of these, TFIIA, is involved in the earliest events during transcription complex assembly. We have purified TFIIA from wheat germ and characterized it in an in vitro transcription system. Wheat TFIIA is a single polypeptide of Mr approximately 35 kd which functionally replaces human (HeLa) TFIIA to form a wheat/HeLa transcription system. [This polypeptide can be eluted from a SDS-polyacrylamide gel, refolded to a native conformation, and will function as wheat TFIIA in the heterologous system.] The heterologous system requires a lower optimal incubation temperature than the HeLa system. Biochemical characterization, using the adenovirus major late promoter, indicates that transcription reaction parameters for both wheat and HeLa TFIIA are similar but the kinetics of transcription for both TFIIAs are somewhat dissimilar. A plant viral promoter, the cauliflower mosaic virus 35S promoter, accurately and efficiently directs in vitro transcription in both the wheat/HeLa and HeLa systems with identical transcription kinetics. We conclude that TFIIA function has been conserved during evolution.

Chromatography, Gel↗