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Biomedical subjects

K Isaacs

Publications and source records attributed to K Isaacs.

18 recordsLinked to original sources
PubMed2000

Safety and efficacy of recombinant human interleukin 10 in chronic active Crohn's disease. Crohn's Disease IL-10 Cooperative Study Group.

BACKGROUND & AIMS: Interleukin (IL)-10 is a cytokine with potent anti-inflammatory properties. We investigated the safety and efficacy of different doses of human recombinant (rhu)IL-10 in patients with Crohn's disease (CD). METHODS: A prospective, multicenter, double-blind, placebo-controlled study was conducted in 329 therapy-refractory patients with CD. Clinical improvement was defined by a reduction of the Crohn's Disease Activity Index (CDAI) by 100 points or more and clinical remission by a decrease of the CDAI to <150 points. At selected centers, patients underwent ileocolonoscopies and activation of the nuclear factor-kappa B (NF-kappa B) system was assessed in biopsy specimens. RESULTS: Subcutaneous treatment with rhuIL-10 over 28 days induced a fully reversible, dose-dependent decrease in hemoglobin and thrombocyte counts but no clinically significant side effects. No differences in the induction of remission were observed between rhuIL-10 groups (1 microg, 18% [9.6-29.2]; 4 microg, 20% [11.3-32.2]; 8 microg, 20% [11.1-31.8]; 20 microg, 28% [18-40.7]; and placebo, 18% [9.6-29.6]). Clinical improvement was observed in 46% (33.7-59) in the 8-microg/kg rhuIL-10 group in comparison with 27% (17-39.6) in patients taking placebo. Responders to rhuIL-10 showed inhibition of NF-kappaB p65 activation in contrast to nonresponders. CONCLUSIONS: Up to 8 microg/kg of rhuIL-10 was well tolerated. A tendency toward clinical improvement but not remission was observed in the 8-microg/kg dose group. Further studies should delineate which subgroups of patients with CD benefit from rhuIL-10 therapy.

Adult↗
PubMed1998

Pattern and morphogenesis in skin.

Models dealing with the development of hair and feather follicles commonly predict that the factors initiating morphogenesis also specify patterns of follicle distribution. The factors have been postulated as chemical or mechanical instabilities which, at certain threshold concentrations, determine both the location of follicles and their form. The models tend to focus on the earliest waves of induction, where follicles develop at separate, non-randomly spaced initiation sites in skin. However, in many animals, there are later waves of initiation, some of which give rise to compound follicles. These are bundles of follicles that arise by branching from the necks of those formed earlier and share a common pilary canal when mature. In some species, compound follicles make the greatest numerical contribution to the follicle population. Measurements of the frequencies of single and branched follicles in sheep selection lines with different follicle densities (from previous studies by Moore et al.) revealed that the follicles which formed first during foetal life (primary and original secondary populations) were established at separately identifiable sites in the skin, called here "initiation sites". However, there were also later waves of development, contributing follicles exclusively by the process of branching (the derived secondary population). Final follicle densities were not correlated with the densities of initiation sites. The observations suggested that mechanisms specifying the positional values of initiation sites differed from those determining follicle number. The final densities of the follicle populations in the sheep lines were also highly negatively correlated with the diameters of the wool fibres grown. The close statistical relationship suggested that the two parameters were developmentally linked. However, whereas fibre characteristics are realised when the follicle is mature, density is established earlier, during foetal life. We have reconciled these observations with the following hypothesis: a population of cells, committed to a follicular pathway of development, differentiates in the skin at or before the first wave of initiation. Subpopulations of the committed cells subsequently participate in each follicle initiation event, the number in each subpopulation ultimately determining fibre dimensions. Follicle initiation continues until most or all of the original population have been utilised. Transplantation and skin recombinant studies have demonstrated that the cells forming the dermal papilla of the follicle participate in follicle initiation and have inductive effects on epidermal tissue. Papilla size is also correlated with fibre diameter in the mature follicle. These attributes are consistent with those described for the committed cell population.

Animals↗
PubMed1998

Interactions between epidermal growth factor and the Tabby mutation in skin.

Mutations of the X-linked genes Tabby (Ta) in mice and EDA in humans result in developmental and functional abnormalities, primarily in the skin and hair follicles. Although both genes are believed to encode membrane-associated proteins, it has been suggested that, in the mouse, the mutation is linked to a deficiency of epidermal growth factor (EGF). This study investigated relationships between the skin abnormalities of Ta mice and the EGF signal pathway. The distribution of endogenous EGF in tissues of Ta/Y and +/Y animals was examined and, because of its reported morphogenetic actions and ability to overcome receptor signalling defects in vivo, the effects of exogenous EGF on the hair follicle population were determined. EGF levels were similar in a number of tissues of Ta/Y and +/Y mice, but amounts in Ta/Y submaxillary glands were reduced, probably due to a smaller gland size. Exogenous EGF inhibited hair follicle development and decreased follicle density in both genotypes. It was concluded from comparisons of the distributions of EGF and its effects in skin with those in mice bearing mutations in the EGF signal pathway that the normal phenotype results from interactions between EGF and the Ta peptide in skin.

Animals↗
PubMed1996

Pneumatosis intestinalis. Two case reports and a retrospective review of the literature from 1985 to 1995.

Pneumatosis intestinalis (PI) is characterized by subserosal or submucosal gas-filled cysts of the gastrointestinal tract. The course may be benign or may lead to the need for urgent surgery. Knowledge of the differential diagnosis, course, and treatment modalities are key in providing optimal care to patients who present with this entity. In this article, two cases of "benign" pneumatosis seen at our institution over a one-month period are presented, along with a retrospective review of the English literature from January 1985 to March 1995. Incidence, symptoms, gross and microscopic appearance, radiographic appearance, etiology, differential diagnosis and therapy are reviewed.

Aged↗
PubMed1995

Crohn's disease. Pilot study comparing MRI of the abdomen with clinical evaluation.

Fourteen patients underwent magnetic resonance imaging (MRI) examination (16 studies) and clinical evaluation concurrently. MRI studies included gadolinium enhancement and TI-weighted fat-suppressed spin echo. Separate investigators determined the severity of disease on MR images and on clinical evaluation in a blinded fashion. MRI studies were evaluated for percentage of mural contrast enhancement, wall thickness, and length of diseased bowel. An MR product was generated using these parameters. Clinical evaluation used the Crohn's Disease Activity Index (CDAI) and modified Index of the International Organization for the Study of Inflammatory Bowel Disease (IOIBD). Linear correlation was found between the MR product and clinical indexes of disease activity. The correlation between MR product and the modified IOIBD index was statistically significant (R(2) = 0.633, p = 0.0012). The correlation of MR product and CDAI was less close (R(2) = 0.274, p = 0.0373). Among individual MR parameters, length of diseased bowel showed the greatest correlation with CDAI (R(2) = 0.537, p = 0.012). Percentage contrast enhancement and bowel wall thickness showed significant correlation to the modified IOIBD index (R(2) = 0.739, p = 0.021) but not to the CDAI (R(2) = 0.004, p = 0.825). The results of this study show that the product of mural contrast enhancement, wall thickness, and length of diseased bowel correlated with clinical indexes of disease activity in Crohn's disease. Our findings suggest that MRI may be useful in evaluating the severity of Crohn's disease and may provide information complementary to clinical evaluation.

Adult↗
PubMed1994

Sex and gender bias in anatomy and physical diagnosis text illustrations.

OBJECTIVE: To examine the sex and gender distribution of illustrations in two atlases, five anatomy texts, and five physical diagnosis texts. DESIGN: Of 4060 illustrations that were identifiable by sex and gender in 12 commonly used anatomy and physical diagnosis textbooks, 3827 were categorized by two reviewers as female, male, or neutral. RESULTS: Females were represented, on average, in 21.2% of the anatomy text illustrations; males were represented, on average, in 44.3%; 34.4% of the illustrations were neutral. Of the nonreproductive anatomy illustrations, a mean of 11.1% (range, 4.6% to 23.8%) depicted women and 43.1% (range, 35.4% to 56.2%) depicted men. Of nonreproductive anatomy illustrations, a mean of 45.8% (range, 27.2% to 59.9%) were neutral. Overall, the physical diagnosis text illustrations demonstrated a more equal sex and gender distribution (21.5% female and 24.8% male). However, in the reproductive chapters of the physical diagnosis texts, females were depicted in a mean of 71.1% (range, 63.2% to 79.0%) of the illustrations, while in the nonreproductive chapters, females were depicted in 8.8% of total illustrations. CONCLUSIONS: In anatomy and physical diagnosis texts, women are underrepresented in illustrations of nonreproductive anatomy. The finding that males are depicted in a majority of nonreproductive anatomy illustrations may perpetuate the image of the male body as the normal or standard model for medical education.

Female↗
PubMed1993

Distribution of acidic and basic fibroblast growth factors in ovine skin during follicle morphogenesis.

Acidic and basic fibroblast growth factors (aFGF and bFGF) have been localized by immunochemistry in ovine skin during wool follicle morphogenesis. At 40 days of gestation, prior to the appearance of follicle primordia, bFGF immunoreactivity was detected in the intermediate and periderm layers of the epidermis and at the dermal-epidermal junction. Antibodies to aFGF did not bind to skin at this age. During early follicle formation, at 76 days of gestation, both FGFs were found in the epidermis and associated with the follicle primordia. Antibodies to aFGF, in particular, bound to the basal cells of the epidermis and the follicle cell aggregations. With the development of epidermal plugs, bFGF was confined to the intermediate layers of the epidermis and the dermal-epidermal junction, whereas aFGF staining was associated with the cells of the epidermis and the plugs. At 90 days, when many different stages of follicle development were in evidence, immunoreactivity for both FGFs was associated with the cells of the elongating epidermal column, particularly those adjacent to the dermal-epidermal junction. During follicle maturation, bFGF was found in the suprabasal layer of the epidermis, in the outer root sheath of the follicle and in the basement membrane zone surrounding the bulb matrix. Conversely, strong staining for aFGF was observed in the epidermis and pilary canal contiguous with the epidermis, and in cells of the upper bulb matrix of the follicle in the region of the keratogenous zone. Western blotting of extracts of mature follicles that had been isolated from the skin showed the presence of a major aFGF immunoreactive band with an apparent molecular mass of 27 kDa.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Localization of epidermal growth factor immunoreactivity in sheep skin during wool follicle development.

Interactions among the cells and matrices of the epidermis and mesenchyme of skin are essential for hair follicle initiation and development. The identification of receptors for epidermal growth factor (EGF) on epithelial components of the follicle during growth has suggested that the ligand participates in some of these events. We have used affinity-purified antibodies together with an alkaline phosphatase detection procedure to investigate the distribution of EGF in the skin of the sheep during wool follicle formation. Immunoreactivity was restricted to the periderm and intermediate layers of fetal epidermis at 55 d of gestation, when the first wave of wool follicles are initiated. This particular distribution persisted during subsequent development but never became associated with the basal cells of the epidermis. The activity was lost around 118 d, coinciding with sloughing of the periderm. No immunoreactivity was found in the plugs or the dermal condensations of the developing follicles. At approximately 105 d of gestation, however, reactions were detected in the outer root sheath as the follicles matured and in the differentiating cells of the sebaceous glands. A similar distribution pattern was also noted at 140 d, just prior to birth, and in adult animals, indicating that EGF was sequestered and perhaps synthesized within the follicle. The presence of immunoreactive material was also associated with the pilary canals and the skin surface, suggesting that this may have had its origin in the sebaceous glands. We examined this using a radioreceptor assay for EGF. Material washed from the skin surface and sebaceous gland extracts were found to displace 125I-EGF from rat liver membranes, in parallel with mouse EGF.

Animals↗
PubMed1991

Hair growth induction: roles of growth factors.

The hair follicles of eutheria arise during fetal life as a consequence of interactions between the cells and matrices of the epidermis and mesenchyme. In some instances, communication may be mediated by growth factors, receptors, and similar molecules. We have focused on epidermal growth factor and fibroblast growth factor, since both are expressed in skin, where they are presumed to perform regulatory functions. In sheep, EGF receptors are located on skin epithelia. An EGF-like protein was detected by immunochemistry in fetal epidermis but was not associated with the cells of developing wool follicles. During subsequent development the molecule was associated with the sebaceous glands and the outer root sheath. If the ORS may be considered a source of stem cells for the proliferating matrix, EGF may act as a differentiation factor, determining cell fates by cell contact mechanisms similar to those in invertebrates. FGF was localized in the epidermis and basal lamina and in follicle plugs during morphogenesis. At maturity, FGF was found in the ORS and in the region of the basal lamina of the follicle bulb, suggesting a role in bulb proliferation and fiber growth.

Aging↗
PubMed1988

A protocol to evaluate the fibrogenic potential of inhaled materials.

A protocol to provide a more rapid assessment of the fibrogenic potential of an inhaled particulate has been developed. Young rats are exposed nose-only for 6 h/day, 7 days a week for 28 days to a respirable aerosol of the test compound. After exposure the rats are kept for up to 1 year, followed by histopathological assessment of the lung. Interim sacrifices could allow an estimate of the rate and severity of the development of any fibrogenic lesion. The protocol has been evaluated for chrysotile asbestos, alpha-quartz and titanium dioxide using rats of both sexes and two different ages at first exposure. The results indicate that there are no significant differences in either the rate, type or extent of lesion provoked by a 28-day exposure period when compared with the more conventional 1-year exposure period studies. It can be concluded that neither sex nor age at first exposure cause any biologically significant differences in response, although young rats would be used in practice. Only one sex need be investigated. The protocol offers considerable benefits over conventional inhalation studies for fibrogenicity (where a 1-year exposure period followed by a further 1-year holding period is usual) by virtue of time, specificity (in the absence of continued exposure the development of any lesion can be studied free from initial inflammatory response) and cost, and could be incorporated into a standard subacute inhalation study design. The results obtained are also of more physiological relevance than studies based on intratracheal instillation.

Administration, Inhalation↗
PubMed1983

Hepatic plasma membranes from genetically obese (ob/ob) mice: studies on fluorescence polarization, phospholipid composition and 5'-nucleotidase activity.

Hepatic plasma membrane lipids of lean (+/?) and obese (ob/ob) mice have been investigated using 1,6-diphenylhexatriene (DPH). Arrhenius plots of DPH fluorescence polarization in membranes showed the breakpoint in obese mice was reduced from 21 to 15 degrees C, whereas the breakpoint of 5'-nucleotidase activity was raised from 23 to 32 degrees C. Arrhenius break temperatures of DPH polarization and 5'-nucleotidase activity responded differently to housing mice at 34 degrees C and triiodothyronine (T3) treatment. Studies of DPH polarization in liposomes and phospholipid fatty acid composition suggested that differences in sphingomyelin acyl composition determine Arrhenius characteristics of hepatic 5'-nucleotidase in lean and obese mice.

5'-Nucleotidase↗
PubMed1981

MMPI correlates of affective disorders.

Compared 24 unipolar depressives with 24 chronic intermittent depressives on the MMPI. The mean profiles did not differ significantly. However, an MMPI clinician was able to sort the profiles, at an above-chance level, into two groups. The rules for such classification are stated. The results are contrasted with the findings of significant differences between unipolar and bipolar depressives. The hypothesis is offered that unipolar and chronic depressives may not differ on severity of symptomatology.

Depressive Disorder↗
PubMedDate not supplied

A possible effect of testosterone on the adenosine 3'-5' cyclic monophosphate levels in rat cerebral cortex. A brief note.

Based on a correlation of serum testosterone levels and cortical cyclic-AMP concentrations in a normal aging population of male CD Fischer rats and a demonstration of decreased cortical cyclic-AMP subsequent to injection of testosterone, it was concluded that a cause and effect relation between hormone concentrations and brain cyclic nucleotide levels is tenable.

Aging↗