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Biomedical subjects

M Moran

Publications and source records attributed to M Moran.

At least 55 records · Page 3Linked to original sources
PubMed1996

The effects of human hippocampal resection on the serial position curve.

The purpose of this study was to examine the contribution of the human hippocampal formation to the classic serial position curve. Seventy-seven patients who underwent anterior temporal lobectomy (ATL) (47 left, 30 right) were administered a list learning task before and after surgery, and changes in the serial position curve were examined. Forty nonsurgical patients with complex partial seizures were tested at comparable intervals and served as controls. Changes in the serial position curve were seen only after left ATL, and almost exclusively among patients without hippocampal sclerosis. Patients without left hippocampal sclerosis, and who therefore underwent resection of hippocampus that was to a considerable degree structurally (and presumably functionally) intact, showed significant declines in recall from the primacy and middle portions of the list compared to all other groups. There was no change in the recency portion of the list. Patients with left hippocampal sclerosis showed only a modest decline in recall from the middle region compared only to the control group, and the right ATL groups did not show any significant changes in serial position recall. These findings demonstrate the contribution of the left hippocampus to those discrete portions of the serial position curve which rely on secondary memory, and have implications for assessing the effects of ATL on memory function.

Adult↗
PubMed1996

Eye movements in spectrum personality disorders: comparison of community subjects and relatives of schizophrenic patients.

OBJECTIVE: The purpose of the current study was to test the specificity of an association between eye tracking abnormality and schizophrenia spectrum personality symptoms in the family members of schizophrenic patients. The studies of biological markers for genetic vulnerability to schizophrenia, which test an association between a biological measure and schizophrenia spectrum personality symptoms, are constrained, since these personality symptoms may lack the specificity for a schizophrenic phenotype. An association between a behavioral measure and these personality symptoms in general can easily be false (i.e., not related to schizophrenic vulnerability). In contrast, a strong deviant finding in the relatives of schizophrenic patients with spectrum personality symptoms, in the presence of a relatively normal finding in spectrum subjects without a known history of schizophrenia, makes the biobehavioral measure an interesting candidate for such investigations. METHOD: Seventy-five subjects recruited from the community who did not have a family history of psychosis completed the study (24 of the 75 had significant schizophrenia spectrum personality symptoms). Thirty-two first-degree relatives of schizophrenic patients (13 with spectrum symptoms) completed the study. Subjects were 18-45 years old and had no DSM-III-R axis I diagnosis. RESULTS: Qualitative smooth pursuit eye movement score was significantly worse in relatives with the spectrum symptoms than in spectrum subjects without a family history of schizophrenia and the nonspectrum relatives. Schizotypal and schizoid symptoms explained a significant amount of the variance in the eye tracking measure in the relatives (31% and 20%, respectively) but not in the community subjects (less than 2%). Relatives of schizophrenic patients with and without the spectrum symptoms had significantly longer antisaccade latency, in spite of comparable latency for visually guided saccades, than the community subjects. CONCLUSIONS: Smooth pursuit abnormality in subjects with schizophrenia spectrum personality disorders is specifically associated with a family history of schizophrenia.

Adolescent↗
PubMed1996

Association of abnormal smooth pursuit eye movements with the deficit syndrome in schizophrenic patients.

OBJECTIVE: The authors' goal was to test the hypothesis that abnormal smooth pursuit eye movements in schizophrenic patients are associated with the deficit syndrome. METHOD: The eye movements of 24 normal comparison subjects, 32 patients with nondeficit schizophrenia, and 11 patients with deficit schizophrenia were tested with infrared oculography using foveapetal step-ramp targets. RESULTS: The group of schizophrenic patients had normal latency to pursuit onset, abnormally decreased open-loop acceleration and abnormally decreased velocity during the periods of closed-loop acceleration and steady-state pursuit. The subgroup of schizophrenic patients with the deficit syndrome had particularly poor performance during the periods of open- and closed-loop acceleration. CONCLUSIONS: Patients with schizophrenia have abnormal smooth pursuit eye movements in response to a step-ramp stimulus, and the defects are particularly pronounced in patients with the deficit syndrome. Abnormal smooth pursuit eye movements in schizophrenia and related disorders have been consistently linked with primary and enduring negative symptoms.

Adult↗
PubMed1996

Isolation of high-molecular-length DNA from human skin.

An agarose plug method for isolating high-molecular-length DNA from mammalian tissues has been developed, including from those that are difficult, such as skin. It gives high yields of DNA that contain a minimum of single-strand breaks and is readily digested by restriction and other nucleases. The method requires only simple equipment and is readily adaptable to field or clinical studies.

Adult↗
PubMed1996

"Diverticula" of anterior mitral valve leaflet as a cause of subvalvular aortic stenosis.

A 77-year-old male patient presented with symptoms of shortness of breath, fatigue, chest pain on exertion and dizziness. Transthoracic echocardiography suggested the presence of a diaphragmatic type of obstruction in the subaortic area of the left ventricular outflow tract. The systolic peak gradient at rest was 34 mmHg with a mean of 23 mmHg. Cardiac catheterization demonstrated rounded radiolucencies in the left ventricular outflow tract in the form of two "pouches" that moved back and forth causing subaortic stenosis. There was also a 70% stenosis of the left anterior descending coronary artery. Left ventricular function was normal. At surgery, a transesophageal echocardiogram demonstrated two distinct pouches arising from the anterior leaflet of the mitral valve. The larger of the two originated near the free edge of the leaflet and was attached via a chord to the membranous septum traversing the subaortic area of the left ventricular outflow tract. The patient underwent a left internal mammary to left anterior descending bypass graft, excision of the larger pouch and over-sewing of the smaller pouch. The excision and repair were performed through the aortic root and aortic valve. The patient made an uncomplicated recovery and on follow up his symptoms disappeared. This case shows the excellent results that can be obtained by surgery of diverticula of the mitral valve causing intermittent subaortic stenosis, a rare pathologic entity, morphologically different from the classical diaphragmatic subaortic stenosis.

Aged↗
PubMed1995

Transferrin-antibody fusion proteins are effective in brain targeting.

In the present study, the receptor binding potential of transferrin (Tf) was linked to an antibody binding specificity. Human Tf was fused to mouse-human chimeric IgG3 at three positions: at the end of heavy chain constant region 1 (CH1), after the hinge, and after CH3. The resulting Tf-antibody fusion proteins were able to bind antigen and the Tf receptor. The CH3-Tf fusion protein showed no complement-mediated cytolysis but possessed IgG receptor I (Fc gamma RI) binding activity. Most importantly, all of the fusion proteins demonstrated significant uptake into brain parenchyma, with 0.3% of the injected dose of the hinge-Tf fusion protein rapidly targeted to the brain. Recovery of iodinated CH3-Tf fusion protein from the brain parenchyma demonstrated that the fusion proteins can cross the blood-brain barrier intact. The binding specificity of these fusion proteins can be used for brain delivery of noncovalently bound ligands, such as drugs and peptides, or for targeting antigens present within the brain.

Animals↗
PubMed1995

Preclinical evaluation of LU 79553: a novel bis-naphthalimide with potent antitumor activity.

LU 79553 is a novel bis-naphthalimide which is highly cytotoxic in vitro with EC50 (concentration required for 50% inhibition of growth) ranging from 2 x 10(-7) to 5 x 10(-10) M. A number of studies were conducted to examine its antitumor activity in human xenograft models. In addition, we wanted to explore the possible schedule dependency of LU 79553 cytotoxicity in these xenograft models. Complete regression of MX-1 (mammary carcinoma) xenografts was observed when LU 79553 was administered i.v. daily for 5 doses at 20 mg/kg (2 cycles starting on Days 6 and 20) or every 3 days for 2 doses at 55 mg/kg (2 cycles starting on Days 6 and 13) or every 7 days for 4 doses. Complete regression was also seen in the MX-1 model when tumors were staged at 1-2 g prior to the initiation of treatment. Regressions (complete or partial) were observed in the LX-1 (lung), CX-1 (colon), DLD (colon), and LOX (melanoma) xenograft models. A significant increase in the median survival time of OVCAR-3- (ovarian carcinoma) bearing mice was noted in LU 79553-treated animals (treated/control = 195%). The excellent activity of this compound in such a wide variety of tumor types suggests LU 79553 merits further investigation in clinical trials.

Amides↗
PubMed1995

Isolation and expression pattern of a cDNA encoding a cathepsin B-like protease from Nicotiana rustica.

Sequence analysis of a 1.33 kb clone from a root cDNA library of Nicotiana rustica revealed an open reading frame encoding a protein of 356 amino acids. The deduced protein has high levels of homology to human cathepsin B protease and a cathepsin B-like cysteine protease from wheat but much lower levels of homology with other plant cysteine proteinases. Southern blotting experiments suggest a limited number of cathepsin B-like genes are present in the genome of N. rustica and also that of N. tabacum. RNA analysis involving a range of tissues, harvested from both Nicotiana species 4-5 h after the beginning of a 16 h photoperiod, revealed the cathepsin B-like gene was being expressed strongly in roots, stem and developing flowers but weakly in mature leaves. Further analysis of RNA extracted from leaf tissue of N. tabacum revealed the gene showed rhythmic expression and also that its expression increased in response to wounding. Analysis of leaf tissues harvested during the latter part of a 16 h photoperiod (11 and 16 h after illumination commenced) showed that transcript levels were two three times higher than in leaf tissue harvested either towards the end of the dark period or 5 h after illumination commenced. When leaf tissue was wounded at 11:00 (5 h after plants were illuminated), and harvested for RNA extraction 6 h later, the level of cathepsin B-like transcript in mesophyll tissue was found to be increased ca. 2-fold relative to the level detected in unwounded controls.

Amino Acid Sequence↗
PubMed1995

Alcohol consumption among HIV-infected patients.

This prospective, cohort study analyzed the prevalence of alcoholism and patterns of alcohol intake over time in a cohort of HIV-infected patients, predominantly homosexual/bisexual men. One hundred eleven HIV-positive subjects were recruited from a comprehensive HIV clinic associated with a large Midwestern university hospital. Each participant completed the Michigan Alcoholism Screening Test (MAST) survey and a standardized quantity-frequency questionnaire on alcohol intake at enrollment. The quantity-frequency scale was repeated every six months for a total of 30 months. Forty-five of the 111 subjects (41%) met the criteria for alcoholism, as defined by a MAST score 5 or higher. There was a significant decrease in alcohol consumption over time, from 6.4 drinks/week in the initial time period to 3.9 drinks/week by the final time period (p < 0.001).

Alcohol Drinking↗
PubMed1995

Determination of the enantiomer of a cholesterol-lowering drug by cyclodextrin-modified micellar electrokinetic chromatography.

The development, optimization and application of a chiral CE (capillary electrophoresis) method for the determination of the enantiomer content of a new cholesterol-lowering drug (BMS-180431-09) is discussed. The chiral CE technique, cyclodextrin-modified micellar electrokinetic chromatography (CD-MEKC), was employed with hydroxypropyl beta-cyclodextrin as the chiral selector in the run buffer. The detection limit of the unwanted enantiomer was about 0.06% w/w. The effect of various parameters on the separation, validation data and examples of the application of the chiral CE method are included.

2-Hydroxypropyl-beta-cyclodextrin↗
PubMed1995

Predictors of response to desipramine in dysthymia.

Little is known about factors that may predict the response of dysthymia or other forms of chronic depression to treatment with antidepressant medication. We investigated several sociodemographic and clinical variables for their relationship to the acute treatment response to desipramine in subjects with DSM-III-R dysthymia. Subjects with DSM-III-R dysthymia were treated with desipramine in an open fashion for 10 weeks. Various clinical and sociodemographic variables were assessed at baseline. Ratings of depressive symptoms and severity and determination of categorical outcome were done during treatment. Baseline extended family adjustment as measured by the Social Adjustment Scale Self-Report was significantly better in the responders compared with the nonresponders (2.1 +/- 0.5 vs. 2.6 +/- 0.8; t = 2.84, df = 52.11, p = 0.006). There was a trend (p = 0.06) for overall baseline social impairment (SAS-SR) to be higher in nonresponders versus responders. Older age was a significant predictor of higher depressive severity (Cornell Dysthymia Rating Scale) and global impairment in the last week of the study. No other variable significantly distinguished responders from non-responders. Although few of the variables that were examined were found to affect acute treatment response, better extended family adjustment as reported on the SAS-SR was a significant predictor of good acute treatment response to desipramine in patients with dysthymia.

Adult↗
PubMed1995

Which way kaikai blo umi? Food and nutrition in the Torres Strait.

The people of the Torres Strait suffer a disproportionate level of diet-related disease, especially diabetes. The Torres Strait Health Strategy identified the difficulty in obtaining healthy food, particularly fruit and vegetables, as a major problem for people living in the Torres Strait. This study examined traditional plant food supply systems and current local production of fruit and vegetables. The supply system of fruit and vegetables from mainland Australia was also examined. Traditional garden food production was seen to continue (mainly to provide food for ceremonial occasions), but had declined because of easy access to store foods, changes in the physical, social and economic environment, limited access to land and water, and quarantine restrictions on movement of garden produce. Supplies of fruit and vegetables from the Australian mainland were infrequent and the prolonged transit time meant that produce was often in poor condition on arrival and prone to continued rapid deterioration due to limited store-level storage facilities. Demand for fresh produce exceeded supply.

Agriculture↗
PubMed1995

Three faces of the health care state.

That health care is a subsystem of the welfare state has dominated the study of states and health care policy. But this conception omits two other faces of the state--as a putatively democratic organization and as the manager of industrial economies in a capitalist world. Policy can be analyzed fruitfully in terms of the tensions between these three faces of the health care state.

Cross-Cultural Comparison↗
PubMed1995

Meningeal melanocytoma. An uncommon diagnostic pitfall in surgical neuropathology.

OBJECTIVE: To describe the neuropathologic findings in four cases of meningeal melanocytoma, a rare benign melanocytic tumor of the central nervous system. DESIGN: Retrospective analysis of surgical pathology and autopsy material. RESULTS: Grossly, all four tumors were well-circumscribed pigmented lesions, and three of four were attached to dura. Microscopically, the neoplasms were composed of spindle cells with epithelioid foci. Mitoses were not seen and only one case exhibited minimal necrosis. Immunohistochemistry and electron microscopy demonstrated the melanocytic nature of the lesions; all four cases showed S100 protein and neuron-specific enolase staining, and three cases exhibited melanoma-specific antigen staining. Immunostaining for epithelial markers and vimentin was uniformly negative. The single case in which electron microscopy was performed demonstrated premelanosomes. CONCLUSIONS: Meningeal melanocytoma is a benign pigmented neoplasm that can easily be confused with melanoma, especially on frozen section analysis. Practicing surgical pathologists should be aware of this entity.

Adolescent↗
PubMed1994

Functional properties of antibody insulin-like growth factor fusion proteins.

Genetic engineering and expression techniques have been used to produce antibody growth factor fusion proteins. Insulin-like growth factors (IGFs) 1 and 2 have been fused to mouse-human chimeric IgG3 at the end of CH1, immediately after the hinge, and at the end of CH3. Fusion heavy chains of the expected molecular weight were expressed, assembled with a co-expressed light chain, and secreted. The resulting molecules continued to bind antigen; they also bound the growth factor receptors, albeit with decreased affinity. The molecule with IGF1 attached after CH3 (CH3-IGF1) had reduced ability to carry out complement-mediated cytolysis. In contrast the molecule with IGF2 attached after CH3 (CH3-IGF2) showed an approximately 50-fold increase in its ability to effect complement-mediated cytolysis and so should be an effective cytolytic agent. Both CH3-IGF1 and CH3-IGF2 bound Fc gamma RI with affinity similar to that of IgG3. The growth factor fusion proteins showed small but significant uptake into the brain parenchyma.

Animals↗
PubMed1994

Experimental photoaging in C3H/HeN, C3H/HeJ, and Balb/c mice: comparison of changes in extracellular matrix components and mast cell numbers.

Chronic exposure of human or murine skin to ultraviolet B (UVB) radiation alters dermal extracellular matrix composition and increases the number of mast cells and inflammatory cells. Experiments were designed to test the possible role of UVB-induced tumor necrosis factor-alpha in these photoaging changes based on reports that C3H/HeN, but not C3H/HeJ or Balb/c mice, produce excess TNF-alpha in response to UVB exposure. Pigmented C3H/HeN and C3H/HeJ strains were exposed to a total of 75 J/cm2 of UVB radiation, and unpigmented Balb/c mice were exposed to 19 J/cm2. The UVB-induced increases in collagen, glycosaminoglycans, and neutrophil number were similar or the same in all three strains. The elastin increase was greater in C3H/HeJ than in C3H/HeN mice. The most striking difference between the strains was a 7.7-fold UVB-induced increase in mast cells in C3H/HeN mice compared to no increase in irradiated C3H/HeJ mice and a 2.3-fold increase in Balb/c mice. These results suggest that excess TNF-alpha (or other mediator) produced in C3H/HeN skin (but not C3H/HeJ skin) in response to UVB exposure is involved in the mast cell increase and partial inhibition of elastin increase, but that neither these mediators nor mast cell products are important mediators for the chronic UVB-induced increases in neutrophils, glycosaminoglycans, and collagen. When a possible source of the excess TNF-alpha was investigated, it was found that isolated epidermal cells from all three strains produced increases in TNF-alpha in response to UVB radiation. These results, as well as the previous results showing differences between these strains in UVB-induced effects on cutaneous immune function, are consistent with a model in which UVB-induced mediators from the epidermis stimulate another cell type to produce excess TNF-alpha (and other mediators) in the C3H/HeN but not C3H/HeJ or Balb/c mice.

Animals↗