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Biomedical subjects

J H Grant

Publications and source records attributed to J H Grant.

At least 19 recordsLinked to original sources
PubMed2001

The transforming growth factor-beta 3 knock-out mouse: an animal model for cleft palate.

The recent report of a transforming growth factor-beta 3 (TGF-beta 3) knock-out mouse in which 100 percent of the homozygous pups have cleft palate raised the question as to the potential usefulness of these animals as a model for cleft palate research. The specific aim in this study was to carefully document the anatomy of the cleft palate in the TGF-beta 3 knock-out mice as compared with wild type controls. Special attention was paid to the levator veli palatini muscle, the tensor veli palatini muscle, and their respective innervation. Because the TGF-beta 3 knock-out is lethal in the early perinatal period and because the heterozygotes are phenotypically normal, polymerase chain reaction was required to genotype the animals before mating. Time-mated pregnancies between proven heterozygotes were then delivered by cesarean section at gestational day 18.5 to prevent maternal cannibalism of homozygote pups. All delivered pups were killed and their tails processed by polymerase chain reaction to verify genotype. The heads were then fixed and sectioned in axial, coronal, or sagittal planes. Sections were stained with hematoxylin and eosin or processed for immunohistochemistry with nerve specific protein gene product 9.5 and calcitonin gene-related peptide antibodies. Sections were analyzed in a serial fashion. Nine wild type control animals were analyzed along with nine TGF-beta 3 knock-out homozygotes. Time matings between proven heterozygotes yielded wild type pups, heterozygote pups, and homozygote knock-out pups in the expected mendelian ratios (28 percent to 46 percent to 26 percent; n = 43). The results demonstrated 100 percent clefting in the homozygous TGF-beta 3 knock-out pups. Complete clefting of the secondary palate was seen in four of nine and incomplete clefting was seen in five of nine. The levator veli palatini and tensor veli palatini muscles were demonstrated coursing parallel to the cleft margin in all cleft mice. The orientation of these muscles differs from the normal transverse sling of the levator veli palatini muscle and the normal palatine aponeurosis of the tensor veli palatini muscle at the soft palate in control animals. Innervation of the levator veli palatini muscle by cranial nerve IX and the tensor veli palatini muscle by cranial nerve V were demonstrated in both cleft and control animals by use of immunohistochemistry with nerve-specific antibodies. Demonstration of a teratogen-free, reproducible animal model of clefting of the palate with a known, single-gene etiology is an important step in the systematic understanding of a congenital defect whose multifactorial etiology has hampered previous research efforts. This study presents a detailed anatomic description of such a model, including a description of the muscular anatomy and the innervation of the muscles of the palate. Because of early perinatal mortality, this model has limited applications for postnatal studies.

Animals↗
PubMed2001

The maximally vascularized central pedicle breast reduction: evolution of a technique.

A retrospective review of patient medical records was used to evaluate a surgical procedure for reduction mammaplasty. Information obtained during this review was then used to determine areas of possible improvement in patient selection and in surgical technique. Modifications were made, and a second series of patients was treated according to the new selection criteria, and by a modified surgical technique. The medical records of the second series of patients were reviewed. The two series of patients are compared. The initial series includes a retrospective review of data collected on 43 consecutive patients treated for bilateral macromastia using the central pedicle breast reduction technique of Hester and colleagues. The results of this initial series of patients were reviewed and presented at the Northwest Society of Plastic Surgeons Meeting; Lanai, HI, in 1995. Data obtained from that review, resulted in modifications in patient selection criteria and in operative technique by the senior author (RPR). An additional 110 consecutive patients have been treated using this modified protocol. The authors review the same data for the second series of patients and compare the results of the two series. They illustrate the use of the central pedicle technique in 153 patients. They have used the central pedicle reduction mammaplasty technique of Hester and colleagues as a model to demonstrate evolution in a surgical technique after evaluation of data from the medical record. A 50% reduction in complications and a 35% reduction in operative time were obtained.

Adolescent↗
PubMed1998

Limb-salvage in reconstruction of recalcitrant pressure sores using the inferiorly based rectus abdominis myocutaneous flap.

Pressure sore closure is frequently a reconstructive challenge. This challenge is particularly evident in cases of multiply recurrent sores. In such settings, there are often opportunities to manage the recurrent wounds either by repeated advancement of previous flaps or by design of alternative ones. However, these interventions are not always feasible, and limb amputation with total thigh flap closure must be considered. A review of operative experience with seven such complex pressure sores in seven patients is presented. Each patient had previously suffered a permanent thoracic-level spinal cord injury. Prior attempts at wound closure were unsuccessful. Despite consideration of all described locoregional flaps, no limb-sparing procedure could be designed satisfactorily. As an alternative to either hip disarticulation and total thigh flap coverage or distant free-tissue transfer, we reconstructed the debrided ulcer beds with inferiorly based rectus abdominis myocutaneous flaps. Six of the seven wounds healed primarily, whereas one required repeated debridement and the addition of a gracilis muscle flap to achieve complete closure. Postoperative follow-up has ranged from 6 to 45 months. Each patient has returned to his baseline preoperative activity level with no clinical compromise of abdominal wall function. All wounds have healed. Successful application of the inferiorly based vertical rectus abdominis myocutaneous flap for cases of both recalcitrant ischial and trochanteric pressure sores is demonstrated and its consideration is advocated if no reconstructive options short of extremity amputation and total thigh flap coverage exist for such challenging sores.

Activities of Daily Living↗
PubMed1992

5-Azacytidine treatment of HA-A melanoma cells induces Sp1 activity and concomitant transforming growth factor alpha expression.

Evidence indicates DNA methylation as a part of the regulatory machinery controlling mammalian gene expression. The human melanoma cell line HA-A expresses low levels of transforming growth factor alpha (TGF-alpha). TGF-alpha mRNA accumulated, however, in response to DNA demethylation induced by a nucleoside analog, 5-azacytidine (5-azaC). The importance of DNA methylation in the TGF-alpha promoter region was examined by a transient transfection assay with luciferase reporter plasmids containing a portion of the TGF-alpha promoter. 5-azaC treatment of HA-A cells before the transfection caused a significant increase in the luciferase activity. Since input plasmids were confirmed to remain unmethylated, DNA demethylation of the TGF-alpha promoter itself does not account for the observed increase in TGF-alpha mRNA. Using an electrophoretic mobility shift assay, enhanced formation of protein-TGF-alpha promoter complex was detected in response to 5-azaC treatment. This 5-azaC-induced complex was shown to contain the transcription factor Sp1 by the following criteria: the protein-DNA complex formed on the TGF-alpha promoter contained immunoreactive Sp1; the mobility of the complex in an electrophoretic mobility shift assay was similar to that formed by recombinant Sp1; and DNase I footprinting analysis demonstrated that the 5-azaC-induced complex produced a footprint on the TGF-alpha promoter identical to that of authentic Sp1. These observations suggest that 5-azaC induces TGF-alpha expression by augmenting the Sp1 activity. However, neither the Sp1 mRNA nor its protein was induced by 5-azaC. These results suggest that in HA-A cells, TGF-alpha expression is down-modulated by DNA methylation. In addition, this process may involve the specific regulation of Sp1 activity without altering the amount of the transcription factor.

Azacitidine↗
PubMed1986

A study of the human immune response to Lolium perenne (rye) pollen and its components, Lol p I and Lol p II (rye I and rye II). I. Prevalence of reactivity to the allergens and correlations among skin test, IgE antibody, and IgG antibody data.

In a stratified random sample of 320 white adults, the prevalence of puncture skin test positivity (ST +) to Lolium perenne (rye grass)-pollen extract (LPE) was 16%. Fifteen percent of all subjects (or 84% of subjects classified LPE IgE antibody positive [Ab +]) was classified IgE Ab + to highly purified Lol p I (Rye I), and 4% of all subjects (or 26% of subjects classified LPE IgE Ab +) was classified IgE Ab + to highly purified Lol p II (Rye II). These data and similar results obtained in an allergy-enriched group of 361 subjects are consistent with previous studies that Lol I is a major allergen and Lol II is a minor allergen of LPE. Whether we studied LPE, Lol I, or Lol II, responder subjects were younger than nonresponder subjects and more male than female subjects were responders. We then investigated the quantitative interrelationships among ST, IgE, and IgG Ab responsiveness to LPE, Lol I, and Lol II in the allergy-enriched group. For each allergen, log-log correlations were strong and significant for ST versus IgE Ab and for IgE Ab versus IgG Ab. All subjects IgE Ab + to Lol I or Lol II were IgG Ab + to that allergen, supporting other evidence for a commonality in the genetic control influencing the production of IgE and IgG Abs to a given allergen. Log-log correlations among ST end points, IgE Ab levels, or IgG Ab levels were strong for LPE versus either Lol I or Lol II but weak between Lol I and Lol II, consistent with the reported lack of cross-reactivity between Lol I and Lol II. Despite these findings, almost all Lol II + subjects were Lol I + by ST (98%), IgE Ab (91%), and IgG Ab (83%), suggesting that the Ia-restricted immune recognition of both these molecules is at least in part under a common genetic control.

Adult↗
PubMed1973

Pornography.

Explore the source record for details and available documents.

Erotica↗
PubMedDate not supplied

Expression of Melan-A in Spitz, pigmented spindle cell nevi, and congenital nevi: comparative immunohistochemical study.

The expression of the antibody Melan-A in 27 benign melanocytic skin lesions (10 congenital nevi, 10 Spitz nevi, and 7 pigmented spindle cell nevi) was compared to that of S100 protein and HMB-45. To evaluate the role of Melan-A in differentiating melanocytic and nonmelanocytic lesions we assessed a number of benign nonmelanocytic skin lesions including neurofibromas, granular cell tumors, and dermatofibromas. Melan-A had an identical staining pattern to S100 protein in the melanocyte population of all lesions, but had the advantage of only staining cells of melanocytic lineage and no other cell types. HMB-45, although staining the junctional components of all lesions with a junctional component, showed varied intensity and distribution in the dermal components. Melan-A is much cleaner than S100 protein, having no background staining, and in skin appears to be specific for melanocytes. The nonmelanocytic lesions did not express Melan-A.

Antigens, Neoplasm↗
PubMedDate not supplied

Cones of skin occur where hypertrophic scar occurs.

Hypertrophic scarring is devastating for the patient, however the pathophysiology and treatment remain unknown after decades of research. The process follows deep dermal injury, occurs only on certain body parts, does not occur in the early fetus or in animals, and is a localized event. This suggests that an anatomic structure in human, deep dermis may be involved. The dermis is a matrix perforated by cones containing many structures including skin appendages and fat domes. We hypothesized that studying the cones might reveal a structure related to scarring. We examined tangential wounds from various body parts on human cadavers along with skin histology from various human body parts, the early fetus, partial thickness burns, hypertrophic scars, and two other species-rats and rabbits. We found that the cones may in fact be the structure. They exist where hypertrophic scar occurs-cheek, neck, chest, abdomen, back, buttock, arm, forearm, dorsal hand, thigh, leg, dorsal foot, helix and ear lobe. They do not exist where hypertrophic scar does not occur-scalp, forehead, concha, eyelid, palm, early fetus, and in rat, or rabbit. It also became apparent that the cones have been omitted from most considerations of skin histology. We suggest that the cones need to be studied in relation to hypertrophic scarring and restored to skin diagrams.

Adult↗
PubMedDate not supplied

Adrenal cytomegaly: quantitative assessment by image analysis.

Adrenal cytomegaly was found in 23 or 0.8% of 2711 pediatric autopsies, including a 13-year-old girl with leukemia and a 20-year-old woman with cystic fibrosis. Cytomegaly of pancreatic islet and acinar cells and pituitary cells was also noted. DNA quantitation by image analysis indicates that cytomegalic cells of the adrenal cortex, pancreas, and pituitary contain increased amounts of DNA (hyperdiploid aneuploid), with adenocytes containing over 25 times the normal amount of DNA in some instances. These data and morphological features suggest that cytomegaly is a reflection of polyploidy due to either partial DNA replication or partial DNA replication plus other modes of polyploidization. Although the mechanism(s) by which these changes evolve remains unknown, regressive processes do not seem to be directly involved. We speculate that polyploidization is, in this setting, a response to physiological demand, a concept that also has relevance to the interpretation of morphology and DNA ploidy profiles of endocrine tumors.

Adolescent↗