PubMed Health⌕ Search

Biomedical subjects

S S Dalal

Publications and source records attributed to S S Dalal.

16 recordsLinked to original sources
PubMed2006

High gamma power is phase-locked to theta oscillations in human neocortex.

We observed robust coupling between the high- and low-frequency bands of ongoing electrical activity in the human brain. In particular, the phase of the low-frequency theta (4 to 8 hertz) rhythm modulates power in the high gamma (80 to 150 hertz) band of the electrocorticogram, with stronger modulation occurring at higher theta amplitudes. Furthermore, different behavioral tasks evoke distinct patterns of theta/high gamma coupling across the cortex. The results indicate that transient coupling between low- and high-frequency brain rhythms coordinates activity in distributed cortical areas, providing a mechanism for effective communication during cognitive processing in humans.

Adult↗
PubMed2004

NUTMEG: a neuromagnetic source reconstruction toolbox.

We have developed an analysis toolbox called NUTMEG (Neurodynamic Utility Toolbox for Magnetoencephalography) for reconstructing the spatiotemporal dynamics of neural activations and overlaying them onto structural MR images. The toolbox runs under MATLAB in conjunction with SPM2 and can be used with the Linux/UNIX, Mac OS X, and even Windows platforms. Currently, evoked magnetic field data from 4-D Neuroimaging, CTF, and KIT systems can be imported to the toolbox for analysis. NUTMEG uses an eigenspace vector beamforming algorithm to generate a tomographic reconstruction of spatiotemporal magnetic source activity over selected time intervals and spatial regions. The MEG coordinate frame is coregistered with an anatomical MR image using fiducial locations and, optionally, head shape information. This allows the reconstruction to be superimposed onto an MRI to provide a convenient visual correspondence to neuroanatomy. Navigating through the MR volume automatically updates the displayed time series of activation for the selected voxel. Animations can also be generated to view the evolution of neural activity over time. Since NUTMEG displays activations using SPM2's engine, certain SPM functions such as brain rendering and spatial normalization may be applied as well. Finally, as a MATLAB package, the end user can easily add customized functions. Source code is available at http://bil.ucsf.edu/ and distributed under a BSD-style license.

Electroencephalography↗
PubMed2001

Human collagenase (matrix metalloproteinase-1) expression in the lungs of patients with emphysema.

Pulmonary emphysema is believed to result from an imbalance between proteolytic enzymes and their inhibitors. Multiple studies have examined the presence of various proteases within the bronchoalveolar lavage fluid from patients with chronic obstructive pulmonary disease (COPD). However, to date extensive examination of the lung parenchyma for the expression of destructive enzymes has not yet been determined. The following study examines the lung parenchyma of 23 patients with emphysema and 8 normal control samples for the expression of matrix matalloproteinase-1 (MMP-1), MMP-12, and MMP-9. We report here that interstitial collagenase (MMP-1) RNA, protein, and activity are present in the lung parenchyma of patients with emphysema and not in the lung of normal control subjects. In contrast, metalloelastase (MMP-12) expression is absent in these samples. Immunohistochemistry studies localized MMP-1 to the Type II pneumocyte in patients with emphysema and not normal control subjects or smokers without emphysema. This observation demonstrates that the lung is altered in emphysema such that the Type II pneumocyte secretes MMP-1 and suggests that MMP-1 may be an important enzyme involved in the destruction of the lung in the human disease. In addition, the induction of a proteolytic enzyme within the Type II pneumocyte suggests that the cells within the lung itself are capable of producing degradative enzymes in this disease process.

Adult↗
PubMed2000

Disruption of the myocardial extracellular matrix leads to cardiac dysfunction.

MMP activity with disruption of structural collagen has been implicated in the pathophysiology of dilated cardiomyopathy. To examine the role of this enzyme in cardiac function, a transgenic mouse was created that constitutively expressed human collagenase (MMP-1) in the heart. At 6 months of age, these animals demonstrated compensatory myocyte hypertrophy with an increase in the cardiac collagen concentration due to elevated transcription of type III collagen. Chronic myocardial expression of MMP-1 produced loss of cardiac interstitial collagen coincident with a marked deterioration of systolic and diastolic function at 12 months of age. This is the first animal model demonstrating that direct disruption of the extracellular matrix in the heart reproduces the changes observed in the progression of human heart failure.

Age Factors↗
PubMed1997

Tissue, temporal and inducible expression pattern of haptoglobin in mice.

Haptoglobin (Hp) is a member of the acute phase plasma proteins previously thought to be synthesized solely by the adult liver. The present study analyzes the tissue and temporal expression pattern of endogenous haptoglobin in the mouse and acute phase inducibility in various tissues. The liver is found to be the major site of haptoglobin expression but significant expression levels were also observed in the lung and skin. Acute phase induction by bacterial lipopolysaccharide (LPS) demonstrated that haptoglobin was induced not only in the liver but also in other tissues, including lung, skin, spleen, and kidney. Temporal analyses demonstrated that haptoglobin is expressed during embryogenesis in the liver and is inducible in various tissues surveyed throughout development. Transgenic mice that harbored a 1.05-kilobase (kb) region of the human haptoglobin promoter linked to two different reporter genes gave rise to lung-specific expression in the majority of transgenic lines with minimal liver expression. However, when induced with lipopolysaccharide, the 1.05-kb fragment contained the necessary elements for a response comparable to endogenous expression levels. In conclusion, these studies demonstrate that haptoglobin is not an adult liver specific gene, and its role as an acute phase reactant may well be more diverse than previously suspected.

Acute-Phase Reaction↗
PubMed1995

Collagenase expression in transgenic mouse skin causes hyperkeratosis and acanthosis and increases susceptibility to tumorigenesis.

In a series of transgenic mice, the human tissue collagenase gene was expressed in the suprabasal layer of the skin epidermis. Visually, the mice had dry and scaly skin which upon histological analysis revealed acanthosis, hyperkeratosis, and epidermal hyperplasia. At the ultrastructural level, intercellular granular materials were absent in the transgenic skin epidermis but contact was maintained through the intact desmosomes. Despite a diversity of underlying etiologies, similar morphological hyperproliferative changes in the epidermis are observed in the human skin diseases of lamellar ichthyosis, atopic dermatitis, and psoriasis. Subsequent experiments demonstrate that when the transgenic mouse skin was treated once with an initiator (7,12-dimethyl-benz[a]anthracene) and then twice weekly with a promoter (12-O-tetradecanoylphorbol-13-acetate), there was a marked increase in tumor incidence among transgenic mice compared with that among control littermates. These experiments demonstrate that by overexpressing the highly specific proteolytic enzyme collagenase, a cascade of events leading to profound morphological changes which augment the sensitivity of the skin towards carcinogenesis is initiated in the epidermis.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1994

Rapid isolation of tissue-specific and developmentally regulated brain cDNAs using RNA arbitrarily primed PCR (RAP-PCR).

RNA arbitrarily primed PCR (RAP-PCR) was used to isolate cDNAs that represent developmentally regulated brain-specific genes. Five clones with a restricted pattern of expression were identified and sequenced. Four cDNAs had no obvious homology to the sequences in GenBank. One clone had over 95% homology to a Ca2+/calmodulin-insensitive adenylyl cyclase, a recently cloned gene that was isolated from rat brain and was shown to be expressed only in adult brain and lung. Two novel cDNAs were investigated further by Northern blot analysis and were found to be expressed differentially during development; their expression was confined to the forebrain in the adult mouse. Further characterization by in situ hybridization showed that the mRNA corresponding to one clone was localized to a limited number of differentiating functional structures in the developing nervous system. In the adult brain, this message is confined to the forebrain with the highest level of expression in the cortex. These data suggest that the product of this gene is involved in the establishment of neuronal networks during brain development and in synaptic plasticity in the mature cortex. This work demonstrates that RAP-PCR is a powerful method for the simultaneous detection of differences between multiple RNA populations and, as such, can be used to study differential gene expression in the brain.

Animals↗
PubMed1992

Collagenase expression in the lungs of transgenic mice causes pulmonary emphysema.

Transgenic mice were generated that expressed a human collagenase transgene in their lungs under the direction of the haptoglobin promoter. Histological analysis demonstrated disruption of the alveolar walls and coalescence of the alveolar spaces with no evidence of fibrosis or inflammation. This pathology is strikingly similar to the morphological changes observed in human emphysema and therefore implicates interstitial collagenase as a possible etiological agent in the disease process. Although elastase has been proposed as the primary enzyme responsible for emphysematous lung damage, this study provides evidence that other extracellular matrix proteases could play a role in emphysema. In addition, these transgenic mice are a defined genetic animal model system to study the pathogenesis of emphysema.

Animals↗
PubMed1992

Arbitrarily primed PCR fingerprinting of RNA.

Fingerprinting of RNA populations was achieved using an arbitrarily selected primer at low stringency for first and second strand cDNA synthesis. PCR amplification was then used to amplify the products. The method required only a few nanograms of total RNA and was unaffected by low levels of genomic double stranded DNA contamination. A reproducible pattern of ten to twenty clearly visible PCR products was obtained from any one tissue. Differences in PCR fingerprints were detected for RNAs from the same tissue isolated from different mouse strains and for RNAs from different tissues from the same mouse. The strain-specific differences revealed are probably due to sequence polymorphisms and should be useful for genetic mapping of genes. The tissue-specific differences revealed may be useful for studying differential gene expression. Examples of tissue-specific differences were cloned. Differential expression was confirmed for these products by Northern analysis and DNA sequencing uncovered two new tissue-specific messages. The method should be applicable to the detection of differences between RNA populations in a wide variety of situations.

Animals↗
PubMed1984

Metabolic rate and thyroid status in rats fed diets of different protein-energy value: the importance of free T3.

Oxygen consumption and thyroid hormone status have been investigated in relation to dietary protein and energy intake in young growing rats fed a control diet of 18% protein as well as diets containing 9 and 4.5% protein fed ad libitum and an 18% protein diet fed at a restricted intake for up to 14 days. Measurements of growth rate, food intake and oxygen consumption indicated that the rats fed a 4.5% protein diet ad libitum and those fed restricted amounts of an 18% protein diet have behaved similarly with severely arrested growth and reduced rates of oxygen consumption and food intake. However, the rats fed the 9% protein diet ad libitum differed from the control group only in terms of a reduced growth rate. Among all the rats thyroid hormone status was associated with the metabolic rate only in the case of the concentration of free L-3,3',5-triiodothyronine (T3), which was reduced in the groups fed 4.5% protein and 18% protein (restricted). Total T3 was actually increased in the rats fed 9% and 4.5% protein and unchanged in the restricted group. These differences in the concentrations of free and total T3 appeared to reflect the fact that the binding capacity for T3 increased with decreasing levels of dietary protein. It is concluded therefore that measurement of free rather than total T3 is the appropriate index of physiological thyroid status in protein-energy malnutrition, at least in the rat.

Animals↗
PubMed1982

Muscle protein synthesis in the streptozotocin-diabetic rat. A possible role for corticosterone in the insensitivity to insulin infusion in vivo.

The effect of insulin infusion in vivo on muscle protein synthesis was investigated in rats. In 10-days-streptozotocin-diabetic rats infused in vivo with amino acids and glucose, the rate of protein synthesis per unit of RNA (RNA activity) was markedly decreased. Pre-treatment with large doses of insulin at 17 and 1 h before the infusion fully restored RNA activity to normal. Infusion of insulin for 6 h with amino acids and glucose did not restore RNA activity to normal in the diabetic rats. However, in diabetic-adrenalectomized rats similar infusions of insulin fully restored RNA activity to normal. Measurements of plasma corticosterone concentrations indicated a 50% increase in the diabetic rats. Since pre-treatment with corticosterone suppressed the stimulatory effect of insulin infusion on RNA activity in adrenalectomized rats, and since corticosterone treatment for 6 days suppressed RNA activity even though insulin concentrations were elevated, it is suggested that increased concentrations of corticosterone are responsible for the lag in response to insulin in the diabetic rat. This means that the catabolic effects of glucocorticoids must be also considered together with the catabolic effect of insulin lack in diabetes.

Adrenalectomy↗