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Biomedical subjects

Stephen Cohen

Publications and source records attributed to Stephen Cohen.

11 recordsLinked to original sources

A demographic analysis of vertical root fractures.

Teeth with vertical root fractures (VRFs) have complete or incomplete fractures that extends through the enamel, dentin and pulp, down the long axis of the tooth. Several different variables were investigated and statistically evaluated as to their correlation with the presence of VRFs. Specifically analyzed were gender, tooth location, age, radiographic and clinical findings, bruxism, and pulpal status. The data were collected from three different endodontists, from three different geographic locations, comprising a total of 227 teeth. Although VRFs may occur in conjunction with any of the parameters investigated, only certain factors were found to occur in a significant number of cases. The results indicate that VRFs are statistically more prevalent in mandibular molars and maxillary premolars. They are associated with periradicular bone loss, pain to percussion, extensive restorations, and seem to occur more often in females and older patients. However, VRFs are not necessarily related to periapical bone loss, a widening of the periodontal ligament space, associated periodontal pockets, a sinus tract, particular pulpal status, or bruxism.

Adult↗

A human colorectal explant culture to evaluate topical microbicides for the prevention of HIV infection.

A human colorectal explant culture was developed to assess the safety and efficacy of topical microbicides proposed for use in humans. Because any product marketed for vaginal application will likely be used for anal intercourse, it is important to evaluate these products in colorectal explant tissue. Microbicides tested included cellulose acetate 1,2-benzenedicarboxylate (CAP), PRO 2000, SPL7013, Vena Gel, and UC781, along with their accompanying placebos. Colorectal tissues were exposed to microbicides overnight and either fixed in formalin to evaluate toxicity by histological analysis or placed in 1-(4,5-dimethylthiazol-2-yl)-3,5-diphenylformazan (MTT) to quantitatively determine tissue viability. Histological analysis showed minimal toxicity for CAP, UC781, and Vena Gel. Shedding of epithelium with intact lamina propria occurred for the PRO 2000 and SPL7013 products, and shedding of epithelium and necrosis of the lamina propria occurred in explants cultured with nonoxynol-9. The MTT assay confirmed these results for PRO 2000 (4% and 0.5%), SPL7013 (and placebo), and nonoxynol-9 but also demonstrated reduced viability for CAP. However, viability of tissues treated with all products was not significantly different from that of the medium control. Efficacy of the microbicides was evaluated by measuring human immunodeficiency virus type 1 (HIV-1) infection of explants in the absence or presence of products. All microbicide formulations tested were highly effective in preventing HIV infection. However, explants treated with some of the placebo formulations also exhibited a lower level of infection. Most of the products developed for vaginal application showed minimal toxicity and were effective in reducing HIV-1 infection in colorectal tissues. These results suggest that this model is useful for evaluating the safety and efficacy of topical microbicides when used rectally.

Anti-Infective Agents↗

The growth regulators warts/lats and melted interact in a bistable loop to specify opposite fates in Drosophila R8 photoreceptors.

Color vision in Drosophila relies on the comparison between two color-sensitive photoreceptors, R7 and R8. Two types of ommatidia in which R7 and R8 contain different rhodopsins are distributed stochastically in the retina and appear to discriminate short (p-subset) or long wavelengths (y-subset). The choice between p and y fates is made in R7, which then instructs R8 to follow the corresponding fate, thus leading to a tight coupling between rhodopsins expressed in R7 and R8. Here, we show that warts, encoding large tumor suppressor (Lats) and melted encoding a PH-domain protein, play opposite roles in defining the yR 8 or pR8 fates. By interacting antagonistically at the transcriptional level, they form a bistable loop that insures a robust commitment of R8 to a single fate, without allowing ambiguity. This represents an unexpected postmitotic role for genes controlling cell proliferation (warts and its partner hippo and salvador) and cell growth (melted).

Animals↗

C. elegans serine-threonine kinase KIN-29 modulates TGFbeta signaling and regulates body size formation.

BACKGROUND: In C. elegans there are two well-defined TGFbeta-like signaling pathways. The Sma/Mab pathway affects body size morphogenesis, male tail development and spicule formation while the Daf pathway regulates entry into and exit out of the dauer state. To identify additional factors that modulate TGFbeta signaling in the Sma/Mab pathway, we have undertaken a genetic screen for small animals and have identified kin-29. RESULTS: kin-29 encodes a protein with a cytoplasmic serine-threonine kinase and a novel C-terminal domain. The kinase domain is a distantly related member of the EMK (ELKL motif kinase) family, which interacts with microtubules. We show that the serine-threonine kinase domain has in vitro activity. kin-29 mutations result in small animals, but do not affect male tail morphology as do several of the Sma/Mab signal transducers. Adult worms are smaller than the wild-type, but also develop more slowly. Rescue by kin-29 is achieved by expression in neurons or in the hypodermis. Interaction with the dauer pathway is observed in double mutant combinations, which have been seen with Sma/Mab pathway mutants. We show that kin-29 is epistatic to the ligand dbl-1, and lies upstream of the Sma/Mab pathway target gene, lon-1. CONCLUSION: kin-29 is a new modulator of the Sma/Mab pathway. It functions in neurons and in the hypodermis to regulate body size, but does not affect all TGFbeta outputs, such as tail morphogenesis.

Amino Acid Sequence↗

Complete recovery from refractory immune thrombocytopenic purpura in three patients treated with etanercept.

Management of patients with immune thrombocytopenic purpura (ITP) who have persistent, severe, and symptomatic thrombocytopenia following splenectomy is difficult and empirical. No single agent or regimen provides long-term success for most patients, and for most treatments it is difficult to assess whether benefits outweigh risks. We report three consecutive patients with critical chronic refractory ITP, who responded promptly and completely following treatment with etanercept, an inhibitor of tumor necrosis factor-alpha. These patients had failed 6-11 previous treatments. In the first patient, etanercept was given for its approved indication: a flare of co-existing rheumatoid arthritis. The next two patients were treated with etanercept because of successful outcomes in the previous patients. Although etanercept appeared to be effective treatment for ITP in these 3 patients, the experimental nature of this treatment and the potential risks must be emphasized. On the basis of these case reports, a clinical trial has been initiated to systematically evaluate the efficacy and risks of etanercept in the management of children and adults with chronic ITP.

Adolescent↗

Genetic screen for small body size mutants in C. elegans reveals many TGFbeta pathway components.

In the nematode Caenorhabditis elegans, a TGFbeta-related signaling pathway regulates body size and male tail morphogenesis. We sought to identify genes encoding components or modifiers of this pathway in a large-scale genetic screen. Remarkably, this screen was able to identify essentially all core components of the TGFbeta signaling pathway. Among 34 Small mutants, many mutations disrupt genes encoding recognizable components of the TGFbeta pathway: DBL-1 ligand, DAF-4 type II receptor, SMA-6 type I receptor, and SMA-2, SMA-3, and SMA-4 Smads. Moreover, we find that at least 11 additional complementation groups can mutate to the Small phenotype. Four of these 11 genes, sma-9, sma-14, sma-16, and sma-20 affect male tail morphogenesis as well as body size. Two genes, sma-11 and sma-20, also influence regulation of the developmentally arrested dauer larval stage, suggesting a role in a second characterized TGFbeta pathway in C. elegans. Other genes may represent tissue-specific factors or parallel pathways for body size control. Because of the conservation of TGFbeta signaling pathways, homologs of these genes may be involved in tissue specificity and/or crosstalk of TGFbeta pathways in other animals.

Animals↗

Vertical root fractures: clinical and radiographic diagnosis.

BACKGROUND: Early detection and management of vertical root fractures, or VRFs, remain a vexing issue that has caused needless suffering for patients as well as for dentists. The authors present techniques to aid the dentist in recognizing VRFs. METHODS: During a five-year period, the authors examined 36 patients who had VRFs. Absent control subjects and a larger number of patients, the authors did not design this investigation for statistical analysis. They diagnosed VRFs through dental histories and clinical and radiographic examinations. RESULTS: The study revealed VRFs in 36 teeth, two of which were vital and 34 of which were nonvital (that is, endodontically treated). The 34 VRFs resulted from excessive operative procedures performed in the root canal after endodontic therapy. Thirty-one of these 34 VRFs were caused by poorly designed dowels (too long, too wide or both) or inappropriate selection of the tooth as a bridge abutment; two VRFs were caused by a restoration that exerted lateral pressure on the axial walls of the preparation; and one VRF was caused by overzealous endodontic forces. The VRFs in the two vital teeth were in men who had a history of bruxism or clenching. CONCLUSIONS AND CLINICAL IMPLICATIONS: VRFs can be detected early by listening to the patient's chief complaints, carefully examining periapical and bitewing radiographs and performing a thorough clinical examination.

Adult↗

Treatment of crown fractures with exposed pulps.

Traumatic injuries are a common cause of pulpal damage in anterior teeth. Crown fractures with exposed pulps represent 18 percent to 20 percent of the traumatic injuries that involve the teeth. This clinical study comprised 36 patients, who were referred for 40 crown fractures with pulp exposures. There were 39 maxillary incisors and one mandibular incisor. The partial pulpotomy (Cvek's technique) consists of amputating exposed pulp tissue to a depth of 1 to 2 mm below the point of pulp exposure. After partial pulpotomy, the pulpal wound is covered with calcium hydroxide; and the cavity is sealed with glass ionomer cement or a composite crown. Clinical and radiographic assessment of the hard-tissue barrier was done after three months. Patients were monitored for periods ranging from one to 12 years. The purpose of this clinical report was to evaluate Cvek's technique in the management of coronal fractures with pulp exposures and the long-term outcome of the partial pulpotomy in immature and mature teeth. In virtually all of the cases, this treatment was successful. Careful partial pulpotomy remains a prudent treatment choice with proper case selection.

Adolescent↗

Early radiographic diagnosis of inflammatory root resorption.

Inflammatory root resorption (IRR) is a common sequelae to oral trauma. Anticipating root resorption after trauma and taking some preventive measures may avoid this outcome. Endodontics and radiographic examination play an important role in the early diagnosis and treatment of root resorption. Subtle radiographic clues can lead to timely implementation of appropriate treatment (if any) according to the kind of resorption discovered. This article describes the most current classification of inflammatory root resorption (usually following trauma) and utilizes a clinical study to provide radiographic clues for its early detection.

Adolescent↗