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Biomedical subjects

J L Martin

Publications and source records attributed to J L Martin.

At least 163 records · Page 9Linked to original sources

The long-term impact of the physical, emotional, and sexual abuse of children: a community study.

The associations between giving a history of physical, emotional, and sexual abuse in children and a range of mental health, interpersonal, and sexual problems in adult life were examined in a community sample of women. Abuse was defined to establish groups giving histories of unequivocal victimization. A history of any form of abuse was associated with increased rates of psychopathology, sexual difficulties, decreased self-esteem, and interpersonal problems. The similarities between the three forms of abuse in terms of their association with negative adult outcomes was more apparent than any differences, though there was a trend for sexual abuse to be particularly associated to sexual problems, emotional abuse to low self-esteem, and physical abuse to marital breakdown. Abuse of all types was more frequent in those from disturbed and disrupted family backgrounds. The background factors associated with reports of abuse were themselves often associated to the same range of negative adult outcomes as for abuse. Logistic regressions indicated that some, though not all, of the apparent associations between abuse and adult problems was accounted for by this matrix of childhood disadvantage from which abuse so often emerged.

Adolescent↗

Cloning, localization and induction of mouse brain glycogen synthase.

The cDNA for mouse brain glycogen synthase has been isolated by screening a mouse cerebral cortical astrocyte lambda ZAP II cDNA library. The mouse brain glycogen synthase cDNA is 3.5 kilobases in length and encodes a protein of 737 amino acids. The coding sequence of mouse brain glycogen synthase cDNA shares approximately 87% nucleotide identity and approximately 96% amino acid identity with the muscle isozyme, while the degree of identity is lower with the liver isozyme. The regional distribution of glycogen synthase mRNA determined by in situ hybridization in the mouse brain reveals a wide distribution throughout the central nervous system with highest densities observed in the cerebellum, hippocampus and olfactory bulb. At the cellular level the expression of brain glycogen synthase mRNA is localized both in astrocytes and neurons with, however, the higher levels observed in astrocytes. Vasoactive intestinal peptide and noradrenaline, two neurotransmitters previously shown to induce a glycogen resynthesis in cultured astrocytes, upregulate the expression of glycogen synthase mRNA in this cell type but not in neurons.

Amino Acid Sequence↗

Symptomatic and endoscopic duodenal ulcer relapse rates 12 months following Helicobacter pylori eradication treatment with omeprazole and amoxycillin with or without metronidazole.

AIM: To determine the effect of Helicobacter pylori eradication with omeprazole and amoxycillin, with or without metronidazole, on the 12-month course of duodenal ulcer disease. METHODS: In a randomized; double-blind study, conducted in 19 hospitals, 105 H. pylori positive duodenal ulcer patients were healed and symptom-free following either omeprazole dual therapy (omeprazole 40 mg o.m.+amoxycillin 500 mg t.d.s., OA, eradication rate 46%, n = 52) or omeprazole triple therapy (omeprazole 40 mg o.m.+amoxycillin 500 mg t.d.s.+metronidazole 400 mg t.d.s., OAM, eradication rate 92%, n = 53) for 2 weeks, followed by 2 weeks of omeprazole 20 mg o.m. and a 12-month untreated follow-up period, after which time all patients were endoscoped. Endoscopic and symptomatic relapse rates, and effect on H. pylori status measured using 13C-urea breath test, were determined. RESULTS: During the 12-month untreated follow-up period, the life-table endoscopic relapse rates were 12% (95% CI: 2-22%) and 2% (95% CI: 0-6%) for OA and OAM patients, respectively. By 12 months, life-table symptomatic relapse rates were 22% (95% CI: 13-37%) and 19% (95% CI: 8-30%) for OA and OAM, respectively. In the 12 months untreated follow-up period, 2/69 (3%, 95% CI: 0-7%) patients rendered H. pylori negative had an endoscopic relapse at the end of the 12-month follow-up period, compared with 5/31 (16%, 95% CI: 3-29%) patients remaining H. pylori positive (P = 0.03 between H. pylori positive and negative groups). Twelve of 69 (17%, 95% CI: 8-26%) patients rendered H. pylori negative relapsed symptomatically, compared with 9/31 (29%, 95% CI: 13-45%) patients remaining H. pylori positive (P = N.S. between groups). There was a significant improvement in epigastric pain (P = 0.0001), nausea and vomiting (P < 0.05) between entry to the study and 1, 6 and 12 months post-treatment for both treatment groups. CONCLUSIONS: OAM eradicates H. pylori in significantly more patients than OA, but successful H. pylori eradication with either OAM or OA predisposes to low endoscopic and symptomatic relapse rates for duodenal ulcer patients when followed up for 12 months.

Adult↗

Metabolism of compound A by renal cysteine-S-conjugate beta-lyase is not the mechanism of compound A-induced renal injury in the rat.

Compound A [CF2 = C(CF3)OCH2F], a vinyl ether produced by CO2 absorbents acting on sevoflurane, can produce corticomedullary junction necrosis (injury to the outer stripe of the outer medullary layer, i.e., corticomedullary junction) in rats. Several halogenated alkenes produce a histologically similar corticomedullary necrosis by converting glutathione conjugates of these alkenes to halothionoacetyl halides. To test whether this mechanism explained the nephrotoxicity of Compound A, we blocked three metabolic steps which would lead to formation of a halothionoacetyl halide: 1) we depleted glutathione by administering dl-buthionine-S, R-sulfoximine (BSO); 2) we blocked cysteine S-conjugate formation by administering acivicin (AT-125); and 3) we inhibited subsequent metabolism by renal cysteine conjugate beta-lyase to the nephrotoxic halothionoacetyl halides by administering aminooxyacetic acid (AOAA). These treatments were given alone or in combination to separate groups of 10 or 20 Wistar rats before their exposure to Compound A. We hypothesized that blocking these metabolic steps should decrease the injury produced by breathing 150 ppm of Compound A for 3 h. However, we found either no change or an increase in renal injury, suggesting that this pathway mediates detoxification rather than toxicity. Our findings suggest that the cysteine-S-conjugate-mediated pathway is not the mechanism of Compound A nephrotoxicity and, therefore, observed interspecies differences in the activity of this activating pathway may not be relevant in the prediction of the nephrotoxic potential of Compound A in clinical practice.

Aminooxyacetic Acid↗

Mechanisms, chemical structures and drug metabolism.

From the studies that have been done by many laboratories over the last 2 decades, it is now clear that the toxicities produced by many drugs are due to their reactive metabolites. It is though that, in many cases, reactive metabolites cause toxicity by binding covalently to tissue proteins. However, until recently it was difficult to identify these protein targets. Due to the development of an immunochemical approach, this problem has been overcome, as is illustrated here by studies that have been conducted on the metabolic basis of the idiosyncratic hepatitis caused by the inhalation anaesthetic halothane. The major problem to solve in the future will be to determine how protein adduct formation leads to toxicity. It is possible that protein adduct formation may alter an important cellular function or may lead to immunopathology, as is thought to occur in the case of halothane hepatitis. If an allergic reaction is suspected, purified protein targets of reactive metabolites can serve as antigens for identifying sensitized individuals. This information can be used to prevent not only an allergic reaction to the drug, but possible cross-reactions to other drugs that are structurally related. Another important application of these studies is the design of safer alternative drugs that will not produce structurally similar toxic reactive metabolites.

Chemical and Drug Induced Liver Injury↗

The 'anatomy' of female child sexual abuse: who does what to young girls?

OBJECTIVE: This paper aims to describe the characteristics of sexually abusive acts experienced by female children in order to identify those perpetrators who inflict intrusive and repeated child sexual abuse (CSA). METHOD: Data were collected from a random New Zealand sample of women aged 18 to 65 years who reported CSA, and a similar number of non-abused comparison women. Information on the perpetrator, the type of CSA, and perpetrator strategies were cross-tabulated. RESULTS: The perpetrators were usually young men, well known to the victim or her family. Greater CSA intrusiveness was statistically associated with greater CSA frequency. Father/stepfather abusers were most likely to perpetrate intrusive and frequent CSA. However, family associates and non-paternal relatives were numerically more often reported as perpetrators than fathers/stepfathers. Stranger-perpetrators featured infrequently. CONCLUSION: We conclude that the most frequent and invasive CSA comes from someone well known to the child, particularly a family member or trusted friend. A focus by the courts or health professionals on either incest only (i.e. CSA between biological relatives) or 'stranger danger' will overlook the large categories of CSA perpetrated by secondary relative and family friend abusers.

Adolescent↗

Do mitigating circumstances influence family reactions to physical aggression?

The influence of mitigating circumstances on family reactions to physical aggression was investigated. 40 families, each with a 2- and a 4-year-old child, were observed during home interactions, and parents' and older children's beliefs concerning mitigation were also assessed. Although parents considered sibling physical aggression to be a serious transgression, they believed that mitigated aggression of both of their children was more excusable and they intervened less often to prohibit mitigated than nonmitigated aggression, even when the aggression was severe. Older children also believed that mitigated aggression deserved less punishment. Provocation, reciprocity, and lack of aggressive intent occurred as mitigating circumstances in the observations. When family members' reactions to these individual circumstances were examined, discrepancies arose in judgments of which specific mitigations justified aggression. These findings were discussed in terms of the clarity of a parent's message, children's appraisals of it, differing conflict roles, and society's impact.

Aggression↗

[Fetal growth from the AUDIPOG study. II. Application for the diagnosis of intrauterine growth retardation].

The identification of intrauterine growth retarded infants remains a problem. It is useful to distinguish between small for date which uses the reference of a statistical birthweight limit and intrauterine growth retardation. A study comprising nearly 100,000 births from many French regions allowed a definition of the limits of birthweights taking into account gestational age, sex, birth rank, maternal height and pregravid maternal weight. This new approach distinguished two groups of newborns, the "constitutionaly small" and those who are newly called "growth retarded". The validity of this new classification is discussed.

Adult↗

The effect of a medication alarm device on patient compliance with topical pilocarpine.

BACKGROUND: This study was performed to investigate the use of an electronic medication alarm device (Prescript TimeCap) to enhance compliance in glaucoma patients taking pilocarpine. METHODS: Thirteen subjects were selected who had been diagnosed with open-angle glaucoma and were receiving 1 drop of pilocarpine solution 4 times a day in both eyes. For each subject, the study was divided into 2 30-day phases, one with the medication alarm device and the other without. Thus, each subject served as his or her own control. Compliance was measured based on the amount of pilocarpine used and by patient questionnaire. In addition, the subjects completed a post-study questionnaire regarding the ease of use of the TimeCap and whether it helped them remember to take their medication. RESULTS: When subjects used the TimeCap, they administered an average of 2.867 g (P < 0.0001) more pilocarpine over the 30 days than during the period without it. Subjects also estimated a significant difference in compliance level, 95.8 percent with the alarm device versus 83.1 percent without it (p < 0.01). All subjects reported no difficulty using the TimeCap, and all reported that it helped them remember to take their medication. CONCLUSIONS: These results are highly suggestive that the TimeCap is an effective compliance aid for glaucoma patients on pilocarpine.

Administration, Topical↗

A community's attitudes towards the mentally ill.

AIM: To assess the general community's knowledge of mental illness and personal experience of people with mental illness. METHOD: Three hundred randomly selected Dunedin residents were surveyed by a postal questionnaire. The instruments used to measure attitudes were a shortened form of the Californian attitudes towards mental illness scale (CAMI scale) and a social distance scale. In addition, questions were asked about the respondent's age, gender, marital status, level of education, their main source of opinion, their experience with the mentally ill, and their beliefs about the causes and types of mental illness. RESULTS: Having known a person with mental illness facilitates more intimate relationships with people with a mental illness. Sociodemographic variables did not predict attitudes on the CAMI scale. Most respondents who had been in contact with the mentally ill held informed and enlightened views. CONCLUSION: The community needs and welcomes information on the subject of mental illness and has a positive outlook for the future planning of the rehabilitation of people with mental illness.

Adult↗

cDNA cloning and baculovirus expression of the human liver endoplasmic reticulum P58: characterization as a protein disulfide isomerase isoform, but not as a protease or a carnitine acyltransferase.

The function of a 58-kDa liver microsomal protein (P58) is controversial. To help clarify the physiological function of this protein, particularly in humans, a full-length human liver cDNA clone was isolated, sequenced, and expressed in milligram quantities with the use of a baculovirus expression system. The deduced amino acid sequence of the mature protein contained two thioredoxin-like active site motifs (CGHC) and in its C-terminus a nuclear localization motif (KPKKKKK), and an ER-retention/retrieval motif (QEDL). The mature form of human P58 shared 95% amino acid sequence identity with the deduced amino acid sequences of a bovine liver cDNA, 93% with a murine B lymphocyte cDNA, and 91% with a rat basophilic leukemia cell cDNA. In contrast to reports on the activities of nonhuman forms of P58, the purified expressed human P58 showed no carnitine acyltransferase or protease activities. However, it did have protein disulfide isomerase activity, indicating that the physiological activity of human liver P58 may be attributed, at least in part, to this activity.

Amino Acid Sequence↗

Local anaesthetic on Filshie clips for pain relief after tubal sterilisation: a randomised double-blind controlled trial.

Pain during tubal sterilisation is thought to be due to either ischaemia or pressure at the site of impact of sterilising devices on the fallopian tubes. We have evaluated the effectiveness of an application of 2% lignocaine gel to Filshie clips to relieve postoperative pain. In a randomised double-blind placebo-controlled study, 80 healthy women undergoing tubal sterilisation under general anaesthesia at the County Hospital, Lincoln, UK, were allocated to be sterilised by Flishie clips covered with 2% lignocaine gel or K-Y gel as placebo. Pelvic pain was assessed, with a 100 mm visual analogue scale, at 1 hour, at hospital discharge, and time of first analgesia or any other time analgesia was demanded. The lignocaine-treated group had significantly longer time to first analgesia, less pain at 1 hour, less nausea and vomiting, and shorter recovery time. Fewer lignocaine-treated patients needed additional analgesia and they required fewer opioids. There was no case of failed sterilisation or adverse reaction to lignocaine. The application of local anaesthetic gel to Filshie clips is a safe, non-invasive, and effective method of relieving postoperative pain during laparoscopic tubal sterilisation.

Adult↗

Thioredoxin--a fold for all reasons.

The thioredoxin fold is a characteristic protein structural motif that has been found in five distinct classes of proteins that have the common property of interacting with cysteine-containing substrates.

Amino Acid Sequence↗

Evidence for sub-picosecond heme doming in hemoglobin and myoglobin: a time-resolved resonance Raman comparison of carbonmonoxy and deoxy species.

Separation of the photophysical aspects of the sub-picosecond (sub-ps) time-resolved resonance Raman signal from contributions due to conformation has been achieved by comparing deoxyhemoglobin (Hb) in the T state with (carbonmonoxy)hemoglobin (HbCO), deoxy-beta 4 (beta 4 CO) (All R state), and monomers deoxymyoglobin and (carbonmonoxy)myoglobin (MbCO) [beta 4 consists of a tetramer of four beta-subunits and shows no cooperativity]. In all photolyzed species, Hb*(CO), Mb*(CO), and beta 4*(CO), the iron-histidine out-of-plane mode (vFe-His), indicative of heme doming, achieves 90% of its full intensity in 1 ps. The frequency of this mode (223-228 cm-1) is shifted significantly relative to equilibrium deoxy-Hb (210-216 cm-1) in the T state, but not with respect to either equilibrium deoxy-Mb or deoxy-beta 4. A correlation between the +12 cm-1 bandshift of vFe-His and the -2 cm-1 shift of the electron density marker band (v4 at 1370 cm-1) relative to T-state deoxy-Hb is shown to hold on all time scales, including the sub-picosecond time scale. Photolyzed Hb*(CO) consists of R-state or weakly interacting tetramers on the picosecond time scale and is shown to have properties similar to those of photolyzed Mb*(CO) and beta 4*(CO) on the picosecond time scale. These results establish that heme doming occurs as an ultrafast reaction to ligand dissociation and that heme doming is the primary event in the sequence of conformational changes leading to the cooperative R-->T transition.

Carboxyhemoglobin↗

Functional aspects of ultra-rapid heme doming in hemoglobin, myoglobin, and the myoglobin mutant H93G.

Heme iron out-of-plane displacement following ligand dissociation in hemoglobin, myoglobin, and the proximal cavity mutant H93G is shown to be as rapid as the heme iron out-of-plane vibrational period by sub-picosecond time-resolved resonance Raman spectroscopy. The results demonstrate that the effect of steric repulsion initiated by the spin change of the iron gives rise to heme doming independent of covalent attachment of the proximal ligand to the protein. It is concluded that the protein plays a passive role in the initial ultrafast heme iron motion toward the out-of-plane position observed in the deoxy structure of hemoglobin and myoglobin. The results suggest that the spin change of the heme iron is the primary cause of rapid heme doming and that steric repulsion of the proximal ligand with the heme plays a secondary role in forcing the iron out of the heme plane.

Animals↗

Factors that mediate between child sexual abuse and adult psychological outcome.

The psychological outcome for a random community sample of women who had experienced significant childhood sexual abuse was assessed, using two outcome measures: (i) psychiatric morbidity (measured with the short PSE); (ii) self-esteem. Sexual abused women with a good outcome, i.e. who were not a PSE 'case' or who had high self-esteem were compared with abused women with a poor outcome. This paper describes the post-abuse factors that modified the two outcomes. In general, a range of variables, all correlated with each other in a complex manner, distinguished good outcome subjects from poor outcome subjects. Post-abuse adolescent variables included family factors (poor mother-father and parent-child relationships), high school factors (poor academic, sporting and social performance) and early pregnancy. Women who had a good adolescent relationship with their father did better than expected statistically. Sport emerged as an alternative at secondary school to academic achievement in catalysing a good psychological outcome. Adult factors included the quality of relationship with partner, which was associated with a good outcome on both measures. Current paid employment was linked to high self-esteem but not to lowered psychiatric morbidity, while the converse applied for high socio-economic status. These findings imply that different processes operate for each outcome measure. A clear recognition by the school of childhood sexual abuse may help to provide the opportunity for the girl to experience success in some arena; this in turn may protect her against the likely adult consequences of low self-esteem and increased psychiatric morbidity.

Adaptation, Psychological↗

Vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide potentiate c-fos expression induced by glutamate in cultured cortical neurons.

Previous reports have demonstrated that glutamate stimulates c-fos mRNA expression in primary cultures of mouse cerebral cortical neurons. We show here that vasoactive intestinal peptide (VIP) induces c-fos mRNA expression; however, this effect of VIP is completely inhibited by the noncompetitive NMDA receptor antagonist MK-801, therefore indicating that VIP stimulates c-fos expression in a glutamate-dependent manner. A similar effect was observed with pituitary adenylate cyclase-activating polypeptide27 (PACAP27). At the intracellular level, coactivation of protein kinases A and C mediates the glutamate-dependent stimulation of c-fos expression evoked by VIP, because either H-89 or staurosporin inhibits the effect of VIP as well as that of glutamate. These results point to a "biochemical AND gate" mechanism, which implies the obligatory activation of both protein kinases A and C in the transduction of c-fos expression. In summary, this article provides evidence that VIP and PACAP27 potentiate the effect of glutamate, the principal effector on c-fos expression, suggesting that both peptides can increase the "throughput" or "strength" of glutamate-containing circuits in the cerebral cortex.

Animals↗