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S Mills

Publications and source records attributed to S Mills.

At least 19 recordsLinked to original sources
PubMed1996

Modulation of plus-maze behaviour in mice by the preferential D3-receptor agonist 7-OH-DPAT.

Differences in the behavioural profiles of dopamine D2 receptor antagonists (e.g., haloperidol vs. sulpiride) in a animal models of anxiety have prompted speculation concerning the importance of their relative affinities for D2-like receptor populations. In an initial attempt to investigate the involvement of D3 receptors in anxiety, the present study examined the effects of the preferential D3-receptor agonist, (+/-)7-OH-DPAT (0.01-10.0 mg/kg), on behaviours displayed by male mice in the elevated plus-maze paradigm. An ethological approach incorporating measurement of a range of defensive acts and postures in addition to conventional parameters was used to provide a comprehensive behavioural profile for the compound. Data analysis indicated a significant increase in percentage of open-arm entries at 10 mg/kg and an altered temporal distribution of behaviour at 1-10 mg/kg. Furthermore, risk-assessment measures (stretched attend postures, closed-arm returns) were dose dependently reduced by drug treatment. Although these behavioural changes would be consistent with anxiety reduction, such an interpretation is negated by dose-dependent decreases in all active behaviours (arm entries, rearing, and head-dipping) and by marked increases in entry latencies and nonexploratory behaviour at the highest dose tested. Overall, these effects are remarkably similar to those previously reported for quinpirole, suggesting either that D2 and D3 receptors exert similar behavioural control or that the agents employed are sufficiently potent at D2 receptors to prevent a resolution of D2 and D3 responses.

Animals↗
PubMed1996

HIV risk behavior, street outreach, and condom use in eight high-risk populations.

In this paper we examine risk behavior, exposure to street outreach, and condom use in samples of injecting drug users (IDUs) and high-risk youth. We used systematic sampling methods to produce representative samples of injecting drug users IDUs (five sites) and high-risk youth (three sites). The populations surveyed engaged in high levels of sexual risk behavior: 20% to 46% reported two or more sex partners in the last month. The majority (62% to 97%) knew someone infected with HIV. Condom use rates approached national health promotion goals for nonsteady partners but not for steady or main partners. Having a condom at time of interview was the most consistent predictor of condom use at last intercourse. Many of the respondents have been in contact with street outreach programs and many acknowledged some personal risk for HIV infection. However, most of the injecting drug users and high-risk youth interviewed (and their sex partners) were still at risk through unprotected sex.

Adolescent↗
PubMed1995

Mechanism of inhibition of human leucocyte elastase by beta-lactams. 2. Stability, reactivation kinetics, and products of beta-lactam-derived E-I complexes.

The monocyclic beta-lactams reported by Knight et al. [Knight, W. B., et al. (1992) Biochemistry 31, 8160; Chabin, R., et al. (1993) Biochemistry 32, 8970] as inhibitors of human leucocyte elastase (HLE) produce stable HLE-inhibitor complexes that slowly reactivate with half-lives ranging from less than 1 to 15 h at 37 degrees C. The complexes produced between PPE and two C-3 dimethyl-substituted beta-lactams are less stable than those produced between HLE and analogous C-3 diethyl-substituted lactams. The stability of the HLE-I complexes is governed primarily by the structure of the substituted urea portion of the inhibitors and not by the identity or presence of a leaving group at C-4 of the lactam ring. In some cases substitutions on the urea portion of the inhibitors yielded complexes that displayed biphasic reactivation kinetics. This suggests the presence of at least two different complexes. The stereochemistry of the leaving group at C-4 has a small effect on the stability of the final complex (1.3-2-fold); therefore, the identity of the final complex is dependent upon the initial stereochemistry at that position. The stability of the complexes was relatively insensitive to hydroxylamine, which suggests that the acyl-enzymes are protected from nucleophilic "rescue". The rate of reactivation of the complex derived from L-680,833,[S-R*,S*)]-4-[(1-(((1-(4- methylphenyl)butyl)amino)carbonyl)-3,3-diethyl-2-oxo-4-azetidinyl)ben zeneacetic acid, was pH independent, while the L-684,481, (R)-(1-(((1-(4-methylphenyl)butyl)amino)carbonyl)-3,3-diethyl-2-azeti din one generated complex displayed a pH-dependent reactivation rate. In the latter case, the increase in reactivation rate with pH displayed a pKa of 7.2. This is consistent with the requirement for base catalysis by the active site histidine to regenerate enzymatic activity. Reactivation of the L-680,833-derived complex produced different products as a function of pH, suggesting two different pH-dependent routes of reactivation. At low pH a route that produced primarily the substituted urea is favored, while at higher pH production of two six-membered ring diastereomers competes with urea generation. Thus, the apparent pH independence of the return of activity is the result of two offsetting pathways. Other compounds such as L-670,258, (S)-4-[((((2-naphthylmethyl)amino)carbonyl)-3,3-diethyl-4-oxo-2- azetidinyl)oxy]benzoic acid, reactivate by these two routes as well as by aminolysis by the other urea nitrogen to produce an additional regioisomer. The temperature dependence of the reactivation of the complexes derived from L-684,481 and L-680,833 suggests different mechanisms.(ABSTRACT TRUNCATED AT 400 WORDS)

Chromatography, High Pressure Liquid↗
PubMed1995

Mechanism of inhibition of human leucocyte elastase by beta-lactams. 3. Use of electrospray ionization mass spectrometry and two-dimensional NMR techniques to identify beta-lactam-derived E-I complexes.

A combination of NMR spectroscopy and electrospray ionization mass spectrometry (ESI-MS) was used to probe the identity of beta-lactam-derived complexes with serine proteases. The carbon and proton NMR chemical shifts of the human leucocyte elastase (HLE)-inhibitor complex derived from [4-13C]-L-680,833, [S-(R*,S*)]-4-[(1-(((1-(4- methylphenyl)butyl)amino)carbonyl)-3,3-diethyl-2-oxo-4- azetidinyl)oxy]benzeneacetic acid, were consistent with an sp3 hybridized carbon. The ESI-MS spectrum of the L-680,833-derived HLE-I complex indicated an increase of 333 Da over the mass of the free enzyme. The data are consistent with acylation of the active site serine, loss of p-hydroxybenzeneacetic acid, and formation of a carbinolamine at the carbon deriving from C-4 of the lactam ring. The complexes produced from HLE and the diastereomers of L-680,833 display identical masses. Since the 4R-isomers produce more stable complexes [Green et al. (1995) Biochemistry 34, 14331-14343], these data suggest that these complexes differ in their stereochemistry or conformation. The structural model of the HLE-I complexes derived from the diastereomers predicts that the hydroxyl of the carbinolamine derives from a structurally observed water molecule yielding S-stereochemistry in all cases. In this model, the 4S- and 4R-diastereomers produce complexes that differ by the location of the side chain of a phenylalanine residue. The mass of HLE was increased by that of L-684,481, (R)-1-(((1-(4-methylphenyl)butyl)amino)carbonyl)-3,3-diethyl-2-azetidino ne, which lacks a leaving group at C-4 in the complex derived from this compound. L-691,886, [S-(R*,S*)]-4-[(1-(((1-(4-ethoxyphenyl)butyl)amino)carbonyl)- 3,3-diethyl-4-oxo-2-azetidinyl)-oxy]benzeneacetic acid, produces two complexes of different mass that reactivate with different rates. The mass of the less stable complex is consistent with the acyl-enzyme of 2,2-ethyl-3-oxopropanoic acid while the mass of the more stable complex is analogous to the carbinolamine observed during L-680,833 inactivation. Porcine pancreatic elastase (PPE) produces a complex with a mass consistent with replacement of the C-4 leaving group by water to produce a carbinolamine from L-684,248, [S-(R*,S*)]-4-[(1-(((1-(4-methylphenyl)butyl)amino)carbonyl)-3,3-dimethy l - 2-oxo-4-azetidinyl)oxy]benzoic acid. The C-4 diastereomer, L-684,249, produces two PPE-I complexes with different masses. One of these complexes has a mass identical to the mass of the complex derived from L-684,248 while the mass of the other complex indicates the presence of the entire inhibitor molecule.(ABSTRACT TRUNCATED AT 400 WORDS)

Humans↗
PubMed1995

Surgical management of haemangioendothelioma of the spine.

Four patients with haemangioendothelioma of the spine which was treated surgically are presented. Two were male and two female, mean age 30 years (range 5-60). All tumours were sited in the thoracic spine between T5 and T10; three were primary and one metastatic from a hepatic haemangioendothelioma. Each patient had a significant neurological deficit at presentation; three were paraplegic. A diagnosis of vertebral neoplastic disease was suggested on plain radiographs, and in three cases this was supported by computed tomography or magnetic resonance imaging. Two patients underwent anterior decompression and posterior instrumented stabilisation, one anterior decompression alone and one posterior decompression followed by tumour vessel embolisation and then anterior decompression. Intra-operative blood loss was a significant feature despite the use of hypotensive anaesthetic techniques and local haemostatic agents. Three of the tumours were tested for Factor VIII (a tumour for vascular tumours), and all proved positive. In these, sufficient histological material was available to grade the tumours according to the classification of Campanacci et al. [1]. All were grade II. Three patients recovered completely from paraglegia; one had residual mild spasticity which required the use of a walking aid. The mean improvement in Frankel grade was 2.5 (range 1-4). In two the tumour recurred outside the spine within 18 months; one had subsequently died. The presentation, investigation and results of surgery for haemangioendothelioma of the spine are presented. Particular attention is drawn to the neurological status at presentation, the effect of pre-operative tumour embolisation and the dramatic recovery that can be achieved in these patients following surgery.

Adult↗
PubMed1994

Limited capacity for glyconeogenesis from alanine by diaphragm muscle.

The mammalian diaphragm (Dia) is a unique skeletal muscle because of its chronic contractile activity. Chronically active muscles have higher capacities for glycogen synthesis from lactate and glucose. In this study, the contribution of alanine to glycogen synthesis in the predominantly fast-twitch mouse Dia was determined. Chronically active fast- and slow-twitch muscles from dy2J/dy2J pseudomyotonic mice were also analyzed. Alanine aminotransferase (AlaAT) activity was significantly (P < 0.05) greater in Dia and chronically active gastrocnemius muscle (Gast) than control Gast. 14C-label incorporation into glycogen following in vivo injection of 14C-alanine, was significantly higher in Dia and chronically active Gast than control Gast. A direct incorporation of 14C from 14C-alanine into glycogen is also observed in vitro. The incorporation rate shows a linear concentration dependent relationship and a pH optimum of 6.3. Insulin had no effect on glycogen synthesis from alanine by Dia in vitro. The extensor digitorum longus muscle (EDL) and chronically active EDL and soleus muscle (Sol) had higher rates of glycogen synthesis from alanine than control Sol and Dia. The oxidation of alanine to CO2 was the primary route for alanine metabolism by the Dia. These results demonstrate that the Dia can synthesize glycogen from alanine, but only at low rates.

Alanine↗
PubMed1994

Short apneas and their relationship to body movements and sighs in preterm infants.

To test the hypothesis that there is an association among short apneas (3-10 s), body movements, and sighs, we studied 11 preterm infants (body weight 1,500 +/- 200 g, mean +/- SE; gestational age 30 +/- 1 weeks, postnatal age 28 +/- 5 days) using a flow-through system. A total of 1,166 apneas, 1,024 movements, and 473 sighs were recorded. Of the 1,166 apneas, 460 (39%) were associated with movements, 91 (8%) with sighs, and 226 (19%) with both movements and sighs. The rate of apneas associated with movements and sighs was significantly greater than expected if only a random association had occurred. These differences remained in quiet, rapid eye movement, and indeterminate sleep. The frequency of each of the three events was similar in a given sleep state. Of the 460 movements associated with apnea, 26% preceded, 23% followed, and 51% occurred during apnea. Similarly, of the 315 sighs associated with apnea, 44% preceded and 56% followed apnea. Apneas preceded by movements were longer than those without movements (5.6 +/- 0.2 vs. 4.9 +/- 0.1 s; p = 0.01). Oxygen saturation before apnea with movement (94 +/- 0.1%) was lower than before apnea alone (96 +/- 0.6%; p = 0.02) and also lower than before movement alone (96 +/- 0.1%; p = 0.001). These findings suggest: (1) there is a strong association among short apneas, movements, and sighs in these infants; (2) sighs appear not to be an isolated event and are likely to be part of a more general motor discharge, and (3) these events are accompanied by mild desaturations and bradycardias.(ABSTRACT TRUNCATED AT 250 WORDS)

Apnea↗
PubMed1994

Erythropoietin after bone marrow transplantation.

The anemia associated with bone marrow transplantation is in part related to a relative erythropoietin deficiency. Recombinant human erythropoietin has been studied in different clinical situations. After allogenic bone marrow transplant, recombinant human erythropoietin has enhanced erythroid engraftment and in several studies, decreased transfusion requirement.

Anemia↗
PubMed1994

Endoscopic versus laparotomy management of endometriomas.

OBJECTIVE: To compare the surgical management and follow-up of patients with endometriomas managed by endoscopic surgery versus laparotomy using a retrospective case control format. DESIGN: Endoscopic oophorocystectomies were performed on 36 patients. Chart review of laparotomy oophorocystectomies from 21 patients was conducted. Six-week and 12-month follow-up for evaluation of symptoms, evidence of recurrence, and fertility was available on all subjects. RESULTS: In the endoscopy group, 39 patients had screening laparoscopy for possible endoscopic surgery. Three of this group required laparotomy and 36 patients underwent endoscopic surgery. Chart review identified 21 patients who had undergone primary laparotomy for endometriomas. Patient groups were matched for age, severity of disease, presence of other infertility factors, and absence of perioperative medical suppression. Outcome parameters for each group were: operating time--endoscopy 2.8 hours (+/- 1.2), laparotomy 3.1 hours (+/- 1.8); estimated blood loss--endoscopy 40 cc (+/- 45); laparotomy, 240 cc (+/- 107); recovery time--endoscopy, 6.2 days (+/- 2.5), laparotomy 30 days (+/- 6.8); endometrioma recurrence rate--endoscopy 11.1%, laparotomy 19%; and pregnancy rate--endoscopy 42.8%, laparotomy 46.6%. CONCLUSION: A high percentage of patients with endometriomas associated with advanced endometriosis can be managed effectively by endoscopic surgery.

Adult↗
PubMed1993

Polyorchism.

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Adult↗
PubMed1992

Data management of an inflammatory bowel disease registry.

The history and etiology of inflammatory bowel disease which is characterized by two major disease processes: ulcerative colitis and Crohn's disease, remain unknown. Research is focussing on seven major areas of genetic, environmental and physiologic factors that apparently relate to this disease. Based on this background, a population based Inflammatory Bowel Disease Registry was established in 1987 in the Lehigh Valley area of southeastern Pennsylvania. Consent forms, patient data forms and protocols for operation and implementation were developed, and databases were designed to accommodate demographic, basic history, follow-up and relative history data. The databases were correlated with an IBD registry ID number which both enabled relational analyses and ensured confidentiality of data information. The registry continues to grow, providing feedback for both continued medical research and supportive information for IBD patients and their physicians.

Database Management Systems↗
PubMed1992

Amniotic fluid turbidity: a useful adjunct for assessing fetal pulmonary maturity status.

A rapid, very simple technique for establishing fetal pulmonary maturity status is presented. Among 100 receiving amniocenteses, aspiration of turbid amniotic fluid that would not permit the reading of newsprint through it was associated with a lecithin/sphingomyelin (LS) ratio of greater than or equal to 2.0, or the presence of phosphatidyl glycerol (PG) in 97% (specificity 98%, positive predictive value 97%). The authors conclude that when turbid fluid is aspirated, delay until LS and PG results are known may not be necessary.

Amniocentesis↗
PubMed1991

Smoking initiation in the United States: a role for worksite and college smoking bans.

Data from four National Health Interview Surveys were combined, and a birth-cohort analysis was undertaken to determine the age when regular smoking is initiated. By the age of 25 years, most smokers have already become regular smokers. Among men, the proportion of each birth cohort who become regular smokers has declined at a rate of about 1.0% for each year of birth since 1945. There has been no identifiable decline in successive birth cohorts of women. For those born in the most recent birth cohorts, there was no sex difference in the proportion who became regular smokers. The proportion of smokers beginning to smoke during the secondary-school years (less than or equal to 18 years of age) has increased steadily, especially among people with a high-school education or less. However, in the latest birth cohort (1960-1962), over 18% of ever smokers with at least a high-school education did not start to smoke regularly until their young-adult years (19-24 years of age). If the effect of tobacco-education programs in the schools is to postpone the uptake of regular smoking, it is important to have tobacco policies in place in other areas of society that will maintain non-smoking behavior through the young-adult years. Accordingly, the banning of smoking in colleges, universities, and worksites, as well as in secondary schools, may significantly decrease the proportion of young people who eventually become regular smokers.

Adult↗
PubMed1991

The influence of serum methotrexate concentrations and drug dosage on outcome in childhood acute lymphoblastic leukaemia.

Sequential methotrexate (Mtx) absorption studies were undertaken in 127 children undergoing treatment for childhood non-T acute lymphoblastic leukaemia (ALL) to determine whether serum drug concentration, clearance and dosage affect event free survival (EFS). Higher serum concentration and area under the plasma concentration curve (AUC) were not associated with an improved EFS. Methotrexate clearance was not found to be of prognostic significance. Patients who tolerated only low 6-mercaptopurine (6-MP) doses because of neutropaenia and those who randomly were prescribed higher doses of Mtx had a lower rate of leukaemia relapse after the completion of therapy. This suggests that the use of maintenance therapy in maximally tolerated doses may be associated with an increased survival in childhood ALL.

Administration, Oral↗
PubMed1989

Decreased atrial natriuretic factor receptors and impaired cGMP generation in glomeruli from the cardiomyopathic hamster.

To determine a possible basis for the decreased action of atrial natriuretic factors (ANF) in congestive heart failure, we compared the cardiomyopathic hamster (CMH) in frank congestive failure, and the age-matched, normal, F1B strain of Golden Syrian Hamsters. Scatchard analysis of competitive binding studies revealed two classes of glomerular receptors. The CMH exhibited decreased binding overall and a markedly decreased number of high affinity receptors but comparable receptor affinity compared to the F1B. In contrast, the low affinity receptor population in the CMH had a much greater affinity compared to the F1B while receptor number was similar. Plasma ANF levels were substantially elevated in the CMH compared to the F1B and in-vitro generation of cGMP was significantly lower in the CMH. Such abnormalities could contribute to the resistance to ANF in this disease.

Animals↗
PubMed1989

Modulation of IL-2-induced human B cell proliferation in the presence of human 50-kDa B cell growth factor and IL-4.

Several human T cell derived factors capable of stimulating human B cells to synthesize DNA have been previously described. One such factor exhibits an apparent m.w. of 50,000 Da and has been termed 50-kDa-B cell growth factor (BCGF). In this report, we show that a human B cell proliferation pathway based on the sequential action of anti-mu antibody, 50-kDa-BCGF and IL-2 is inhibited in the presence of human rIL-4. Although IL-4 itself is capable of triggering B cell DNA synthesis as measured at 72 h, this lymphokine inhibits, in a dose-related manner, the 50-kDa-BCGF driven response of B cells to IL-2 when such proliferation is determined after 144 h. This inhibition takes place at an early step of the B cell activation and does not require the presence of IL-4 during the whole culture period. Such inhibitory activity of IL-4 is specific to the IL-2-induced B cell proliferation because DNA synthesis measured in the presence of semi-purified human 12-kDa-BCGF is not affected by the presence of IL-4. Our results suggest that a particular pathway of human B cell activation leading to the proliferation of these cells in the presence of IL-2 could be either up- or down-modulated by 50-kDa-BCGF and IL-4, respectively.

Adjuvants, Immunologic↗