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M McGuire

Publications and source records attributed to M McGuire.

At least 19 recordsLinked to original sources
PubMed1995

Separate site catalysis by pyruvate phosphate dikinase as revealed by deletion mutants.

Previous studies had indicated that pyruvate phosphate dikinase (PPDK), an enzyme which catalyzes the interconversion of adenosine 5'-triphosphate (ATP), orthophosphate (P(i)), and pyruvate with adenosine 5'-monophosphate (AMP), pyrophosphate (PP(i)), and phosphoenolpyruvate (PEP), is made up of 25, 13, 18, and 35 kDa domains [Carroll, L. J., Xu, Y., Thrall, S. H., Martin, B. M. & Dunaway-Mariano, D. (1994) Biochemistry 33, 1134]. The catalytic histidine (which mediates the phosphoryl group transfers from ATP to P(i) and pyruvate) is located on the 18 kDa domain while the 25 and 13 kDa domains appear to contain the ATP binding site and the 35 kDa domain appears to contain the pyruvate binding site, respectively. The goal of this investigation was to examine functional interdependency of the putative ATP and pyruvate binding domains. Two truncated forms of PPDK were created by using recombinant DNA techniques. The 35 kDa (C-terminal) deletion mutant was found to catalyze the E+ATP+P(i)<-->E-P+AMP+PP(i) partial reaction but not the E-P+pyruvate<-->E+PEP partial reaction. The 25 kDa (N-terminal) deletion mutant was found to catalyze the E-P+pyruvate<-->E+PEP partial reaction but not the E+ATP+P(i)<-->E-P+AMP+PP(i) partial reaction. Neither mutant catalyzes the full ATP+P(i)+pyruvate<-->AMP+PP(i)+PEP reaction. These results are interpreted to mean that the ATP and pyruvate binding domains in PPDK are functionally independent, thus providing evidence for separate active sites for catalysis of the two partial reactions.

Base Sequence↗
PubMed1995

Schizotypal symptoms and signs in the Roscommon Family Study. Their factor structure and familial relationship with psychotic and affective disorders.

BACKGROUND: Although schizotypal personality disorder aggregates in relatives of schizophrenic probands, the criteria for this disorder may not be optimal either in describing the dimensions of schizotypal phenomena or in identifying those with a high familial liability to schizophrenia. METHODS: In the Roscommon Family Study, an epidemiologically based family study of major psychiatric disorders conducted in the west of Ireland, we examined 25 individual schizotypal symptoms and signs, assessed by structured personal interview, in 1544 first-degree relatives (without chronic psychosis or mental retardation) of five proband groups: schizophrenia; other nonaffective psychoses; psychotic affective illness; nonpsychotic affective illness; and matched, unscreened controls. RESULTS: We obtained seven meaningful schizotypal factors: negative schizotypy, positive schizotypy, borderline symptoms, social dysfunction, avoidant symptoms, odd speech, and suspicious behavior. Taken individually, all of these factors, except borderline symptoms, significantly discriminated relatives of schizophrenic probands from relatives of controls; in descending order of the odds ratios, they were odd speech, social dysfunction, suspicious behavior, negative schizotypy, avoidant symptoms, and positive schizotypy. In a multivariate analysis, four of these factors remained significant: odd speech, negative symptoms, social dysfunction, and avoidant symptoms. These schizotypal factors differed in their specificity. Three of the four most predictive schizotypal factors also significantly discriminated relatives of probands with other nonaffective psychoses from relatives of controls. CONCLUSION: "Schizotypy" is a complex, multidimensional clinical construct, whose various dimensions differ widely both in the degree and specificity with which they reflect the familial liability to schizophrenia. Subpsychotic thought disorder; negative schizotypal signs, such as poor rapport and odd behavior; deficient occupational functioning; and social isolation/avoidance best characterized relatives of schizophrenic probands compared with relatives of matched controls.

Adolescent↗
PubMed1995

Examining the validity of DSM-III-R schizoaffective disorder and its putative subtypes in the Roscommon Family Study.

OBJECTIVE: The authors sought to assess whether the DSM-III-R category of schizoaffective disorder differs meaningfully from schizophrenia and affective illness in clinical features, outcome, and familial psychopathology. In addition, the authors evaluated the validity of two proposed subtyping systems for schizoaffective disorder: 1) bipolar versus depressive (based on presence or absence of a full manic syndrome in the past) and 2) good versus poor interepisode recovery. METHOD: In the epidemiologically based Roscommon Family Study, index probands with diagnoses of schizophrenia or affective illness were selected from a case registry. Personal interviews were conducted with 88% of traceable, living probands and 86% of traceable, living first-degree relatives. RESULTS: Probands with schizoaffective disorder differed significantly from both those with schizophrenia and those with affective illness on lifetime psychotic symptoms as well as on outcome and negative symptoms assessed as follow-up. Relatives of probands with schizoaffective disorder had significantly higher rates of affective illness than relatives of schizophrenic probands and significantly higher rates of schizophrenia than relatives of probands with affective illness. Probands with bipolar and depressive schizoaffective disorder did not differ substantially with respect to psychotic symptoms, negative symptoms, outcome, or family history. Schizoaffective disorder probands with good interepisode recovery had fewer negative symptoms and a better outcome than those with poor recovery, but there were no significant differences in family history. Both the epidemiologic and family data are consistent with the hypothesis that schizoaffective disorder results from the co-occurrence of a high liability to both schizophrenia and affective illness. CONCLUSIONS: On the basis of the validators examined, DSM-III-R criteria for schizoaffective disorder define a syndrome that differs meaningfully from both schizophrenia and affective illness. The division of schizoaffective disorder into bipolar and depressive subtypes was, however, not validated. The separation of schizoaffective disorder into subtypes based on level of interepisode recovery defined subtypes that differed clinically but not with respect to familial psychopathology.

Adolescent↗
PubMed1994

Isolation and structure/activity features of halomon-related antitumor monoterpenes from the red alga Portieria hornemannii.

Ten halogenated monoterpenes (2-6 and 8-12) related to the novel antitumor compound halomon (1) or to the carbocyclic analog 7 have been isolated from different geographic collections of the red alga, Portieria hornemannii. Structures were assigned to the basis of spectral analyses (primarily NMR and MS). The absolute configuration of isohalomon (2) was further established by X-ray crystallography. The compounds were comparatively evaluated alongside 1 and 7 in the U.S. National Cancer Institute's in vitro human tumor cell line screening panel. The results provide some interesting initial insights into the structure/activity relationships in this series.

Antineoplastic Agents↗
PubMed1994

Clinical heterogeneity in schizophrenia and the pattern of psychopathology in relatives: results from an epidemiologically based family study.

Individuals with schizophrenia vary widely in their symptoms, course of illness and outcome. Family background is the strongest known risk factor for schizophrenia. We know little of the relationship between clinical variability in this disorder and the level of familial vulnerability to schizophrenia and other major mental disorders. Therefore, in schizophrenic probands meeting DSM-III-R criteria (n = 126) from the epidemiologically based Roscommon Family Study, we systematically assessed 9 major symptoms, course, global outcome, Schedule for Negative Symptoms and the Levels of Functioning Scale. These clinical characteristics were related t the risk of mental disorders in first-degree relatives assessed by personal interview or hospital records (n = 354) utilizing both the "familial/sporadic" and the Cox proportional hazard models. Using either statistical method, no consistent and significant relationship was found between any of our measures of symptoms, course or outcome and the risk for schizophrenia or schizophrenia spectrum disorders in relatives. Similarly, no relationship was found between these clinical measures and the risk for affective illness, alcoholism or anxiety disorders. Our results are not consistent with previously articulated hypotheses that negative symptoms or poor outcome in schizophrenia reflect a high familial liability to illness. While familial factors contribute substantially to an individual's vulnerability to schizophrenia, our results suggest that once an individual is affected, these same factors do not strongly influence either the kinds of symptoms displayed or the course and outcome of the illness.

Adult↗
PubMed1994

An epidemiologic, clinical, and family study of simple schizophrenia in County Roscommon, Ireland.

OBJECTIVE: The authors sought to estimate the prevalence of simple schizophrenia, compare the clinical presentations and courses of simple and "typical" schizophrenia, and examine psychopathology in first-degree relatives of probands with simple schizophrenia, probands with typical schizophrenia, and community comparison subjects. METHOD: The authors followed up all individuals with a recorded diagnosis of schizophrenia (N = 285) and 75% of those with a diagnosis of severe affective illness (N = 99) from the Roscommon County Case Register, which includes all individuals seeking psychiatric care in a rural county in western Ireland. The authors interviewed all available first-degree relatives of these groups and of matched unscreened community comparison subjects. RESULTS: Eleven cases of simple schizophrenia were diagnosed in the probands, for an estimated population prevalence and morbid risk in County Roscommon of 5.3 (SE = 1.6) and 6.2 (SE = 1.9) per 10,000, respectively. Individuals with typical schizophrenia (N = 126) had more marked delusions, hallucinations, and positive thought disorder; individuals with simple schizophrenia had more pronounced negative thought disorder and a more chronic course. Neither social/occupational functioning nor negative symptoms differed between the two groups. The risks for schizophrenia and all nonaffective psychoses were greater in the relatives of the probands with simple schizophrenia than in the relatives of the community comparison subjects. CONCLUSIONS: In this sample, simple schizophrenia was relatively rare, was rather debilitating, and resembled typical schizophrenia in presentation and course except for the absence of positive psychotic symptoms. From a familial perspective, simple schizophrenia appears to be related to typical schizophrenia.

Adult↗
PubMed1994

Outcome and family study of the subtypes of schizophrenia in the west of Ireland.

OBJECTIVE: The authors sought to clarify differences in outcome and familial psychopathology among the classical subtypes of schizophrenia. METHOD: In the epidemiologically based Roscommon Family Study, personal interviews were conducted with 88% of traceable living probands (N = 415) an average of 16 years after illness onset and with 86% of traceable living first-degree relatives (N = 1,753). Probands meeting the DSM-III-R criteria for schizophrenia were subtyped by DSM-III-R and ICD-9. RESULTS: By both diagnostic systems, age at onset differed significantly across subtypes, being earliest in the subjects with the hebephrenic and catatonic subtypes and latest in the paranoid subjects. The probands with the paranoid subtype had substantially better outcome, especially in occupational functioning and capacity for self-care. The DSM-III-R criteria for paranoid schizophrenia were considerably more successful than the ICD-9 criteria in selecting good-outcome cases. Neither the risk for schizophrenia nor the risk for schizophrenia spectrum disorders significantly differed in relatives as a function of the proband subtype. The subtypes of schizophrenia did not "breed true" within families. CONCLUSIONS: Paranoid schizophrenia, especially when narrowly defined, as in DSM-III-R, has a substantially better outcome than other subtypes. From a familial perspective, 1) paranoid schizophrenia is not a milder form of schizophrenia and 2) catatonic schizophrenia is probably closely related to typical schizophrenia. The subtypes of schizophrenia are not, from a familial perspective, etiologically distinct syndromes.

Adult↗
PubMed1993

The Roscommon Family Study. III. Schizophrenia-related personality disorders in relatives.

OBJECTIVES: We sought to clarify the familial relationship between five putative schizophrenia-related personality disorders (schizotypal [SPD], paranoid, schizoid, avoidant, and borderline) and schizophrenia, other nonaffective psychoses, and affective illness. DESIGN: A case-controlled epidemiologic family study using DSM-III-R criteria. PARTICIPANTS: Five hundred thirty-four probands selected from a psychiatric case register or electoral register, of whom 415 were personally interviewed, and 2043 living and traceable relatives, of whom 1753 were personally interviewed. RESULTS: Compared with relatives of unscreened controls, relatives of probands with schizophrenia had a highly significantly increased prevalence of SPD, and modest, but significant, increased prevalences of paranoid, schizoid, and avoidant personality disorders. Borderline personality disorder was rare, with a modest clustering of cases in relatives of affective disorder probands. The prevalence of SPD was also significantly elevated in relatives of probands with SPD and with other nonaffective psychoses but not in relatives of probands with psychotic or nonpsychotic affective illness. In contrast to the pattern seen for schizophrenia, the prevalence rate of SPD was substantially greater in parents than in siblings of schizophrenic probands. CONCLUSIONS: Schizotypal personality disorder has a strong familial relationship with schizophrenia. Paranoid, schizoid, and avoidant, but not borderline, personality disorders may have a significant familial relationship with schizophrenia. Schizotypal personality disorder also reflects the familial liability to other psychotic disorders but probably not to affective illness. Fitness effects may substantially influence the pattern of schizophrenia-related personality disorders in relatives.

Adolescent↗
PubMed1993

The Roscommon Family Study. IV. Affective illness, anxiety disorders, and alcoholism in relatives.

OBJECTIVES: This report seeks to evaluate the specificity of the familial liability to schizophrenia by examining in the relatives of the various proband groups the risk for affective illness (AI), anxiety disorders, and alcoholism. DESIGN: A case-controlled epidemiologic family study using DSM-III-R criteria. PARTICIPANTS: Three hundred eighty-four index probands from a psychiatric case register, 150 unselected control probands from an electoral register and 2043 of their living and traceable relatives, of whom 1753 were personally interviewed. RESULTS: In personally interviewed relatives of schizophrenic probands, the lifetime risk for all AI (24.9% +/- 3.8%) or just bipolar AI (1.2% +/- 0.7%) was very similar to that found in interviewed relatives of controls (22.8% +/- 4.0% and 1.4% +/- 0.7%, respectively). However, the risk for all AI (49.7% +/- 12.9%) or bipolar AI (4.8% +/- 3.2%) was substantially increased in relatives of schizoaffective probands. A substantially higher proportion of relatives of schizophrenic vs control probands who had AI demonstrated psychotic--and specially mood-incongruent psychotic--symptoms when affectively ill. Neither the risk for anxiety disorders nor that for alcoholism was increased in relatives of schizophrenic vs control probands. CONCLUSIONS: The familial liability to schizophrenia possesses some specificity and does not substantially increase the risk to AI, anxiety disorders, or alcoholism. Even when narrowly defined, schizoaffective disorder has a substantial familial link to classic AI. The familial liability to schizophrenia predisposes to psychosis, and especially mood-incongruent psychosis, when affectively ill. Finally, these results do not support the hypothesis that, from a familial perspective, schizophrenia and AI are on a single etiologic continuum.

Adolescent↗
PubMed1992

Characterization of the percepts evoked by discontinuous motion over the perioral skin.

The capacity of human subjects to process information about discontinuous and continuous movement was evaluated. Constant-velocity brushing stimuli were delivered through aperture plates that rested lightly upon the mandibular skin. Each plate consisted of either two spatially separated, slit-like openings or a single continuous, longer opening. It was discovered that percepts of smooth apparent motion were achieved with the split apertures (i.e., from discontinuous movement) for only limited ranges of stimulus velocity. Moreover, the optimal velocity supporting smooth apparent motion increased with the separation between the slit-like openings. In a second series of experiments, subjects' ability to discriminate opposing directions of discontinuous and continuous movement was evaluated. It was found that subjects could derive directional information from percepts elicited by discontinuous movement. However, the capacity to discriminate opposing directions of continuous movement cannot be explained solely in terms of the ability to process information about the change in position of a stimulus from its onset to its offset.

Discrimination Learning↗
PubMed1992

An analysis of the diagnostic accuracy of endoscopic biopsy and cytology in the detection of oesophageal malignancy.

The role of combined cytohistological examination in the differentiation of benign from malignant oesophageal mucosal lesions was studied in 331 patients. Malignancy was confirmed by specimen histopathology in 58 patients. Both endoscopic biopsy and cytology were positive in 41 (71%) patients. Endoscopic biopsy alone suggested malignancy in 10 cases (17%) while cytology was positive after negative biopsy in seven (12%). Cytology yielded four false positive and 10 false negative results giving a sensitivity level of 81%, a specificity of 98% and a positive predictive value for oesophageal malignancy of 92%. Histology on the other hand yielded one false positive and seven false negative results providing a sensitivity of 87%, a specificity of 99% and a positive predictive value of 96%. No patients were left undiagnosed using both diagnostic modalities; cytology increased the diagnostic yield from 87% to 100%. Exfoliative cytology was most valuable in the diagnosis of tumours of the lower one-third of the oesophagus where seven of 31 malignancies (23%) were identified by this method alone (P less than 0.05). Neither the histological type of the tumour nor the morphological appearance was found significantly to affect the diagnostic yield (P greater than 0.05). We conclude that cytological examination should be standard practice in the investigation of oesophageal lesions.

Biopsy↗
PubMed1992

Simulated paraphilias: a preliminary study of patients who imitate or exaggerate paraphilic symptoms and behaviors.

In a consecutive series of admissions to the Johns Hopkins Sexual Disorders Unit, 4 out of 20 patients appeared to have simulated paraphilic symptoms that further assessment indicated were either exaggerated or not present. The paper presents case histories of these 4 patients. A descriptive comparison is made between these patients and control groups of patients who admitted having paraphilic symptoms and a group of patients accused of having paraphilic symptoms but who denied them. Patients who simulated paraphilias tended to be self-referred (75%) and without current legal charges (100%). None of these patients was referred or sought treatment for pedophilia, in contrast to the other two patient groups, in which pedophilia accounted for 75% of the referrals. Several possible explanations for why patients might simulate paraphilias and implications for therapists who evaluate or treat sex offenders are discussed.

Adult↗
PubMed1991

Urinary cytology in the detection of bladder carcinoma.

We have analysed the accuracy of cytological examination of voided urine in a population of 265 patients presenting with suspected bladder lesions. Bladder carcinoma was confirmed by tissue histopathology in 51 patients. Of these, 42 were identified correctly by urinary cytology examination. Overall 34 patients were labelled as frankly malignant on cytology, of whom 2 were negative on final histology. 13 patients had been designated as suspicious however with 3 benign on final histological diagnosis. These data give a sensitivity for diagnosis of bladder cancer by urinary cytology of 82%, a specificity of 97%, a positive predictive value of 94%, and a negative predictive value of 96%.

Adolescent↗
PubMed1991

Corticotropin-releasing hormone inhibits maternal behavior and induces pup-killing.

Behavioral responses to stressors and the effects of stressors on maternal behavior change with mothering experience. Corticotropin-releasing hormone (CRH) is released by stressors and produces stress-like behavioral effects. We tested the effects of ICV infusion of ovine CRH (0.5-4 ug) on pup-directed behaviors in ovariectomized, ovarian steroid-treated virgin rats that were either naive to pups or that had three days of mothering experience. CRH inhibited maternal behavior in naive and experienced rats in a dose-related manner. The magnitude and duration of inhibition, especially at the 1 ug dose, were less in rats with mothering experience. Higher doses of CRH (1 - 4 ug) significantly increased pup-killing in rats that were naive to pups. In contrast, CRH produced no pup-killing in rats with mothering experience.

Animals↗
PubMed1991

Effects of acetate dialysate on transforming growth factor beta 1, interleukin, and beta 2-microglobulin plasma levels.

To evaluate potential adverse effects of acetate use in hemodialysis (HD), we measured plasma interleukin (IL-1 alpha, IL-1 beta, IL-6), TNF alpha, TGF beta 1, and beta 2-microglobulin levels with ELISA assays in normal (N = 9), CRF (N = 6), CAPD (N = 7) and HD (N = 8) subjects and compared the effects of acetate (Ac) and acetate-free (Ac-free) dialysate. TGF beta 1 was the only cytokine consistently detected. Compared to normals (median 57, range 53 to 68 pg/ml, one undetected; N = 8), TGF beta 1 was higher in the CRF (75, 70 to 97 pg/ml, one undetected) and CAPD (75.5, 66 to 116 pg/ml, N = 6) groups (P less than 0.05), and was somewhat higher in the HD (68, 52 to 88 pg/ml) group (P less than 0.10). Acutely, TGF beta 1 pre-HD (70, 63 to 88 pg/ml) increased above normals post AcHD [79.5, 65 to 140 pg/ml uncorrected for ultrafiltration (UF)] and was higher after AcHD versus Ac-free HD both uncorrected (79.5, 65 to 140 pg/ml vs. 70, 52 to 86 pg/ml) and corrected for UF (68, 51 to 115 pg/ml vs. 57, 43 to 69 pg/ml; P less than 0.05). beta 2-microglobulin was not different after AcHD (81.2 +/- 8.0 mg/ml) versus Ac-free HD (72.5 +/- 6.9 mg/ml). Significantly lower serum inorganic phosphorus was also found four hours post-AcHD compared to four hours post-Ac-free HD (0.87 mmol +/- 0.10 SEM vs. 1.05 mmol +/- 0.07 SEM; P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Acetates↗
PubMed1991

Electric field stimulation of human osteosarcoma-derived cells: a dose-response study.

In vitro electrical stimulation of human osteosarcoma-derived cells resulted in increased cell adherence and current directed cell migration. We have developed an electrical exposure system in which two steel electrodes imbedded in media-based agar, poured in a standard culture dish, are used to apply electric field signals to cells in culture without ion contamination from the electrodes. The cells were exposed to a 100 Hz pulsed DC electric signal at peak field strengths of 1, 10, 100, and 625 mV/cm in the culture media. The data showed no change in cell adherence at 1 and 10 mV/cm, an increase in adherence at 100 mV/cm, and a decrease in both adherence and cell proliferation at 625 mV/cm. Electric field stimulation in vivo has been found useful in accelerating the healing of fractures and non-unions, and the repair of surgical and cancer-related skeletal defects.

Biophysical Phenomena↗
PubMed1991

The role of aspiration cytologic examination in the diagnosis of carcinoma of the breast.

A study of 2,000 patients who had undergone fine needle aspiration of a solid lump of the breast was conducted to determine the accuracy of this technique. During the period 1982 to 1989, all patients with a solid mammary mass, presenting to a specialized breast unit were initially investigated by fine needle aspiration cytologic examination (FNAC). To date, we present data on 2,000 consecutive aspirations with matching histologic diagnosis on the excised pathologic specimens. In particular, the relationship between tumor histologic factors and the accuracy of cytologic diagnosis was examined. The sensitivity of FNAC in the diagnosis of a malignant growth was 84 per cent; this represents first aspiration results only. The specificity was more than 99 per cent. The rate of acellular or unsatisfactory aspirations was 12 per cent. We had a positive predictive rate for diagnosis in carcinoma of the breast of almost 95 per cent. The diagnosis of lobular and in situ patterns of disease was questioned, with three of three in situ lesions and ten of 23 lobular lesions missed by FNAC. We do not recommend that FNAC replace excision biopsy and frozen section in the diagnosis of carcinoma of the breast.

Biopsy, Needle↗