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Biomedical subjects

E M Smith

Publications and source records attributed to E M Smith.

At least 145 records · Page 8Linked to original sources
PubMed1991

The association between pregnancy and human papilloma virus prevalence.

This study examined the effects of pregnancy on the prevalence of HPV infection, comparing 69 pregnant and 54 nonpregnant age-frequency matched female patients. HPV prevalence was detected by DNA hybridization using the ViraPap/ViraType dot blot procedure. The prevalence of HPV among pregnant women increased with gestational age from 8.0% in the first trimester, to 16.7% in the second, and 23.1% in the third trimester. This finding suggests that HPV infection may be activated by hormonal or other effects of pregnancy and may explain why number of pregnancies is known to be associated with increased risk of cervical dysplasia and cancer. Oncogenic HPV types 16/18 and 31/33/35 were identified with almost equal frequency in the study population whereas HPV 6/11 was seen rarely. The logistic regression models indicate that there were no significant differences between HPV positive and HPV negative groups by age, income, number of sex partners, age of first intercourse, average frequency of intercourse per month, number of pregnancies, oral contraceptive duration, or pregnancy status. There were no interaction effects. A current Pap result of cervical dysplasia (OR = 8.9; 95% confidence interval: 2.1, 38.8), oral contraceptive use (OR = 0.1; 0.03, 0.6), and education (OR = 1.4; 1.1, 1.8) were significant predictors of HPV status.

Adolescent↗
PubMed1991

Role of leukocyte-derived pro-opiomelanocortin peptides in endotoxic shock.

The immune and neuroendocrine systems communicate and maintain homeostasis through various mechanisms, including the use of common signal and recognition molecules and the use of similar processes. This type of integrated network has profound effects on the onset and outcome of certain disease states, including endotoxic shock, in which a cascade of mediators influence the pathophysiologic responses. We have found that some of the common signal molecules shared between the immune and neuroendocrine systems are the peptide hormones adrenocorticotropin (ACTH) and endorphins (END). Our investigations have shown that these molecules are produced in vitro by cells of the immune system treated with various stimuli, including immunological stimuli such as bacterial lipopolysaccharide (LPS; endotoxin), virus infection (Newcastle virus; NDV), and the more classical neuroendocrine stimuli corticotropin-releasing hormone (CRH). We have proposed that the production of END by the peripheral immune system contributes to the pool of opioid peptides associated with the pathophysiology of endotoxic shock. Lymphocytes from LPS-sensitive C3HeB/FeJ mice but not LPS-resistant C3H/HeJ mice produce END and ACTH both in vitro and in vivo after treatment with LPS. Purification of the in vitro produced LPS-induced END from B-lymphocyte spleen cells followed by injections into both LPS-sensitive and -resistant mice elicits changes in body temperature and respiration rate. The spleen cells from the LPS-sensitive mice process ACTH and END differently depending on the stimulus for induction and the cell type in which the processing takes place. CRH or virus induce ACTH 1-39 and beta-END, whereas inductions with LPS yield major products of ACTH 1-22 to 1-26 and gamma-END, products that are for the most part unique to the immune system. We have shown that LPS induces a novel protease that functions optimally at pH 5 to cleave ACTH 1-39 into ACTH 1-22 to 1-26. This enzyme is present in LPS, but not mock or CRH-induced B cells from LPS-sensitive mice. The LPS-resistant mice did not possess this enzyme and therefore produced only the high-molecular-weight pro-opiomelanocortin (POMC)-like molecule. The inability to produce ACTH and END, presumably by their inability to process the precursor, may account, in part, for their lack of response to the LPS. The POMC peptides also may play an indirect role in orchestrating the pathophysiologic response, since both ACTH and END were shown to induce tumor necrosis factor (TNF). Our data strongly suggest that lymphocyte POMC peptides ACTH and END are important mediators in the overall response to endotoxin.

Adrenocorticotropic Hormone↗
PubMed1991

Electroconvulsive therapy revisited.

Electroconvulsive therapy (ECT) remains an extremely valuable tool in the treatment of certain psychiatric disorders. Despite the sensationalism of the past decade, ECT is the treatment of choice in severe depression that is unresponsive to other therapies or in patients who are overtly suicidal. In addition, ECT is particularly valuable in the elderly population, who are at risk for serious complications from the side effects associated with drug therapy. This report describes a case of recurrent depression in which ECT was successfully used.

Aged↗
PubMed1990

Molecular cloning of a cDNA for rat hepatic glutaminase. Sequence similarity to kidney-type glutaminase.

Mammalian liver possesses a unique isozyme of phosphate-activated glutaminase which plays an important role in the regulation of glutamine catabolism. Antibodies to hepatic glutaminase were used to screen a lambda gt11 rat liver cDNA library. One cDNA to hepatic glutaminase was identified. Changes in the relative abundance of hepatic glutaminase mRNA were determined by hybridization to this cDNA. The mRNA is found only in liver; it is not present prior to birth but its abundance increases dramatically at birth. The abundance of the mRNA is increased approximately 4-fold in diabetes. The sequence of the cDNA was compared to that recently published for kidney (brain)-type glutaminase (Banner, C., Hwang, J.-J., Shapiro, R.A., Wenthold, R.J., Nakatani, Y., Lampel, K.A., Thomas, J.W., Huie, D., and Curthoys, N.P. (1988) Mol. Brain Res. 3, 247-254). When the predicted amino acid sequences were compared a region of 123 amino acids with greater than 80% identity was found. The presence of scattered amino acid substitutions within stretches of identical amino acids suggests that the glutaminase isozymes are encoded by separate genes. This is the first demonstration of any similarity between the two glutaminases at the molecular level.

Aging↗
PubMed1990

Distribution of hepatic glutaminase activity and mRNA in perivenous and periportal rat hepatocytes.

Perivenous and periportal hepatocytes were isolated by the digitonin/collagenase perfusion technique. The specific activity of phosphate-activated glutaminase was 2.33-fold higher in periportal cells than in perivenous cells. Similarly, the relative abundance of glutaminase mRNA was 2.6-fold higher in samples from periportal cells. The distribution of glutaminase activity and mRNA was compared with those for glutamine synthetase (predominantly perivenous) and phosphoenolpyruvate carboxykinase (predominantly periportal). The results suggest that phosphate-activated glutaminase is predominantly expressed in the periportal zone of the liver acinus.

Animals↗
PubMed1990

Mononuclear leukocyte glucocorticoid receptor binding characteristics and down-regulation in major depression.

Some patients with major depressive disorder (MDD) have elevated plasma cortisol concentrations and show failure to suppress cortisol secretion upon administration of dexamethasone (DEX), yet they do not have Cushingoid features. To study whether this represents glucocorticoid (GC) resistance, [3H]-DEX-binding assays were used to measure, in vitro, the GC receptor affinity (1/Kd) and number (Bmax) in mononuclear leukocytes of 11 MDD patients and 15 control subjects. No receptor abnormalities were detected in the MDD group; thus any cellular defect leading to a lack of responsiveness to GC in the MDD patients, if present, probably lies beyond the initial receptor binding. DEX (1.0 mg orally) was administered to study in vivo GC receptor down-regulation. Compared to the control group, fewer depressed subjects down-regulated Bmax after DEX. By paired t-test, Bmax decreased significantly in the control group but not in the depressed group. Receptor number on the control day did not correlate significantly with the degree of receptor down-regulation, severity of depression or cortisol concentrations across all the subjects. These results do not lend support to previous reports suggesting that GC resistance in MDD results from a GC receptor-binding abnormality, and they emphasize the importance of considering receptor studies in the context of GC-mediated cell processes in order to identify the exact cellular defect(s) leading to GC resistance.

Administration, Oral↗
PubMed1990

Interaction of immunoactive monokines (interleukin 1 and tumor necrosis factor) in the bivalve mollusc Mytilus edulis.

Mytilus edulis has been the subject of recent studies to determine whether the relationship between the immune and neuroendocrine systems seen in vertebrates also exists in invertebrates. The effects of mammalian monokines were studied in Mytilus immunocytes previously shown to produce and react to opioid peptides. These invertebrate cells respond to interleukin 1 (IL-1) and tumor necrosis factor (TNF), both in vitro and in vivo, in a manner similar to that of human granulocytes. As in the mammalian monokine network, the effect of IL-1 on the immunocytes is brought about, at least in part, by its stimulatory effect on the formation of TNF. In addition, the presence of immunoreactive IL-1 and TNF in Mytilus hemolymph was demonstrated.

Animals↗
PubMed1990

Nucleotide and amino acid sequence of lymphocyte-derived corticotropin: endotoxin induction of a truncated peptide.

To determine the degree of similarity between pituitary and lymphocyte proopiomelanocortin, the lymphocyte mRNA was reverse transcribed, cloned, and sequenced. Murine lymphocyte mRNA was first purified by oligo(dT)-cellulose affinity chromatography and was reverse transcribed by using a selective 3' antisense oligonucleotide primer directed at the boundary between the translated/nontranslated region on the 3' end of exon 3. This cDNA was then amplified in a polymerase chain reaction with selective primers containing Sal I and Kpn I restriction endonuclease sites. Amplified cDNA was then directionally ligated into M13mp18 and M13mp19 bacteriophage and was sequenced. The nucleotide sequence encoding this peptide was identical to that of mouse pituitary corticotropin (ACTH). Elevated levels of lymphocyte immunoreactive ACTH were then induced with bacterial lipopolysaccharide and the peptide(s) was purified by antibody affinity chromatography and reverse-phase high-performance liquid chromatography. The predominant immunoreactive ACTH species was approximately 3 kDa and its sequence was identical to pituitary ACTH(1-25). These results conclusively demonstrate that lymphocytes produce authentic ACTH and harbor its mRNA.

Adrenocorticotropic Hormone↗
PubMed1990

Relationship of one form of human histamine-releasing factor to connective tissue activating peptide-III.

We have previously reported purification of three forms of histamine-releasing factors (HRFs) from mixtures of streptokinase-streptodornase stimulated human mononuclear cells and platelets with apparent molecular masses of 10-12, 15-17, and 40-41 kD (1989. J. Clin. Invest. 83:1204-1210). We have also prepared mouse MAbs against the 10-12-kD HRF (1989. J. Allergy Clin. Immunol. 83:281). Affinity-purified 10-12-kD HRF appears as a broad band upon polyacrylamide gel electrophoresis in the presence of SDS. We determined the NH2-terminal amino acid sequence of the top and bottom halves of this broad band. Sequence analysis revealed striking homology between this HRF and connective tissue activating peptide-III (CTAP-III), a platelet-derived 8-10-kD protein known to cause mitogenesis and extracellular matrix formation in fibroblast cultures. 19 of 21 NH2-terminal residues in the top half of the HRF band were identical to the NH2-terminal sequence of CTAP-III. 20 of 21 NH2-terminal residues in the bottom half were identical to the NH2-terminal sequence of neutrophil-activating peptide-2, which is derived from CTAP-III by proteolytic cleavage between residues 15 and 16. Purified CTAP-III also released histamine from basophils. Rabbit antiserum raised against either native or recombinant CTAP-III recognized affinity-purified HRF in immunodot blot assays, and MAb against HRF recognized CTAP-III in both dot blot and microtiter plate based immunoassays. These data demonstrate the first structural, functional, and immunologic relationship between one form of human HRF and a previously described cell product.

Amino Acid Sequence↗
PubMed1990

Acute postdisaster psychiatric disorders: identification of persons at risk.

This study examined the prevalence of four psychiatric disorders--posttraumatic stress disorder, major depression, generalized anxiety disorder, and alcohol abuse/dependence--in survivors of a jet plane crash into a hotel. Forty-six subjects were interviewed with the Diagnostic Interview Schedule/Disaster Supplement within 4-6 weeks of the event. More than half of the subjects met criteria for a psychiatric disorder after the disaster. More than two-thirds of the cases of acute postdisaster psychiatric disorders were predicted by identifying the subjects who had predisaster psychiatric histories. Predisaster psychiatric disorder predicted postdisaster psychopathology with a sensitivity of 72% and a specificity of 90%.

Adult↗
PubMed1990

Post-traumatic stress disorder in disaster survivors.

In spite of the difficulties inherent in the study of traumatic stress in disaster victims, the benefit of obtaining more knowledge on the subject is potentially great, especially considering the numbers of individuals affected. Recent estimates of the frequency of world-wide traumatic events have determined that almost two million households annually experience damages and/or injuries from fire, floods, hurricanes, tornadoes, and earthquakes alone. The population that is at risk is expected to grow exponentially with our expanding technology, making it even more vital to acquire knowledge to help the growing number of future disaster victims. Additionally, disaster research can contribute to a better understanding of PTSD and human coping processes that can be generalized to more ordinary stress situations. In the meantime, survivors of major catastrophes who experience acute symptoms of PTSD such as insomnia, nightmares, and jumpiness should be observed for nonresolution of symptoms over time, especially if there is a premorbid history of psychopathology or character problems. Otherwise, survivors may benefit from reassurance that PTSD symptoms are common in the short-term postdisaster period and that they can usually be expected to dissipate with time.

Adaptation, Psychological↗
PubMed1990

Connective tissue activation. XXXIV: Effects of proteolytic processing on the biologic activities of CTAP-III.

Microheterogeneity of connective tissue activation peptide III (CTAP-III) was revealed by preparative and analytical isoelectric focusing. Proteolytic activities in human platelet preparations resulted in four cleavage products of platelet-derived CTAP-III. Three isoforms (CTAP-III des 1-13, des 1-14, and des 1-15/NAP-2) stimulate [14C]glycosaminoglycan synthesis; two isoforms also promote [3H]DNA synthesis in human fibroblast cultures. Elastase (from porcine pancreas) cleavage of human platelet-derived CTAP-III and rCTAP-III-Leu-21 to the des 1-15 isoforms was associated with either preservation of specific anabolic biologic activity or an actual increase in specific activity. Nonenzymatic glycosylation of lysyl residues and deamination of the NH2-terminal asparagine of platelet-derived CTAP-III were commonly present, but did not correlate with the biologic activities that were measured. Protein sequence homology shows CTAP-III and its isoforms to be members of a family of proteins (including NAP-1/II-8, MGSA, and platelet factor-4) known to be associated with growth, wound repair, inflammation, and neoplasia. The consequences of proteolytic processing reported here for CTAP-III may be characteristic of the other proteins in this group.

Amino Acid Sequence↗
PubMed1989

Connective tissue activation. XXXIII. Biologically active cleavage products of CTAP-III from human platelets.

Evidence for three new isoforms of CTAP-III from human platelets is presented; two NH2-terminal cleavage products were identified, CTAP-III (des 1-13) and CTAP-III (des 1-15). CTAP-III (des 1-13) has a pI of 8.6 and is a relatively stable proteolytic cleavage product that retains the capacity to stimulate [14C]GAG synthesis in human synovial cell cultures. CTAP-III (des 1-15) appears to be an elastase or chymotrypsin cleavage product and identical to NAP-2, an entity thought to have neutrophil activating properties.

Amino Acid Sequence↗
PubMed1989

Trial of support treatment with human chorionic gonadotrophin in the luteal phase after treatment with buserelin and human menopausal gonadotrophin in women taking part in an in vitro fertilisation programme.

OBJECTIVE: To evaluate the effect of support with human chorionic gonadotrophin in the luteal phase in women taking part in an in vitro fertilisation programme after buserelin and human menopausal gonadotrophin were used to hyperstimulate their ovaries. DESIGN: Controlled group comparison. SETTING: Outpatient department of a private hospital. PATIENTS: 115 Women with indications for in vitro fertilisation, all of whom had at least one embryo transferred. INTERVENTIONS: After suppression of the pituitary with buserelin the ovaries of all the women were stimulated with human menopausal gonadotrophin on day 4 of the luteal phase. Human chorionic gonadotrophin (10,000 IU) was given to induce ovulation, and oocytes were recovered 34 hours later. Embryos were transferred 46 to 48 hours after insemination. Women who had received the 10,000 IU of human chorionic gonadotrophin on a date that was an uneven number (n = 61) were allocated to receive support doses of 2500 IU human chorionic gonadotrophin three and six days after that date. The remaining 54 women did not receive hormonal support. END POINT: Determination of the rates of pregnancy. MEASUREMENTS and main results--Support with human chorionic gonadotrophin did not significantly alter the progesterone or oestradiol concentrations in the early or mid-luteal phase. The mean (range) progesterone concentrations in the late luteal phase in women who did not become pregnant were, however, significantly higher in those who received support (16(9-110) nmol/l nu 8(4-46) nmol/l), and the luteal phase was significantly longer in this group (14 days nu 12 days). The rate of pregnancy was significantly higher in the women who received support than in those who did not (25/61 nu 8/54). CONCLUSIONS: When buserelin and human menopausal gonadotrophin are used to hyperstimulate ovaries support with human chorionic gonadotrophin in the luteal phase has a beneficial effect on in vitro fertilisation.

Adult↗
PubMed1989

Time trends in cancer mortality in the Federal Republic of Germany: progress against cancer?

In accordance with a previous analysis of US cancer mortality, this report also indicates that cancer mortality in the FRG over the last 3 decades (1952-1985) has not shown any decline commencing in a given period and prevailing in all age groups. If present, such effects could have been interpreted as a manifestation of improvements associated with cancer treatment. The absence of such an effect, derived by using data up to 1985 and age-specific mortality rates, supports the view expressed in the US analysis that improvements in cancer treatment are unlikely to have an impact on overall cancer mortality statistics and that efforts toward prevention may be more rewarding.

Age Factors↗
PubMed1989

Differential expression and regulation of thyrotropin (TSH) in T cell lines.

The immune system's production of and response to thyrotropin (TSH) suggests the existence of a hypothalamic-lymphoid-thyroid regulatory axis (HLT). To evaluate the possible roles of lymphocyte-derived TSH we characterized its structure and regulation of production. Using an in vitro system, we screened T cell lines for the production of TSH in response to thyrotropin-releasing hormone (TRH). We identified MOLT 4 T cells as producers of intact TSH based on TSH radioimmunoassay (RIA) displacement and de novo synthesized protein structure similar to pituitary TSH. Northern blot analysis using a cDNA probe to TSH beta showed the existence of an mRNA species similar in molecular size to pituitary mRNA of TSH beta. The MOLT 4-derived TSH is induced in a dose-dependent fashion by TRH and that induction is significantly inhibited by the thyroid hormone, triiodothyronine (T3). HUT 78 T cells express an mRNA species similar to TSH beta but do not express detectable protein suggesting a lack of translation of the mRNA species. The evidence suggests that the MOLT 4 T cells serve as an in vitro model for TSH production and may be used to study differential expression of the genes for TSH in the immune system. Elucidation of this in vitro system will provide information on mechanisms of regulation of an HLT axis that are unique to the immune system as well as pathways common to the immune and neuroendocrine systems.

Cell Line↗
PubMed1989

Angiotensin converting enzyme inhibitors: spirapril and related compounds.

The synthesis of spirapril (5), spiraprilat (25), their RSS stereoisomers, and their glycyl (18b) and lysyl (36, 37) analogues is described. These compounds were evaluated in vivo for inhibition of angiotensin converting enzyme (ACE), and selected compounds were evaluated for in vitro ACE inhibition (spirapril ID50 16 micrograms/kg; spiraprilat IC50 0.8 nM, ID50 8 micrograms/kg). In anesthetized rats, iv, esters 5 and 36 are more potent than enalapril, and diacids 25 and 37 are more potent than enalaprilat in vitro. In the conscious rats, orally, 5 and enalapril (2) showed potent and sustained activity at doses of 0.03-1 and 0.1-1 mg/kg, respectively. From this work, spirapril was selected for clinical evaluation as an antihypertensive agent.

Angiotensin-Converting Enzyme Inhibitors↗