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Biomedical subjects

B D Caldwell

Publications and source records attributed to B D Caldwell.

9 recordsLinked to original sources

Molecular quantification of human beta-glucuronidase levels in a patient with Vohwinkel's syndrome.

The skin must undergo the process of keratinization in order to perform its functions. During the process of differentiation, certain genes are activated while others are repressed, leading to changes in structural proteins and enzymes and in the synthesis of various lipids. An error in any of these steps can ultimately impair the process of keratinization. Vohwinkel's syndrome is the direct result of a defect in keratinization. Patients who have this epidermolytic palmoplantar keratoderma present clinically with hyperkeratosis of the stratum corneum. Hyperkeratosis has been linked to an increase in beta-glucuronidase levels. The authors studied the absolute concentration of human beta-glucuronidase in a patient with Vohwinkel's syndrome as determined through a double-antibody sandwich enzyme-linked immunosorbent assay and a Western blot assay of the blood, urine, and skin of the patient.

Adult↗

Fracture mechanics. A comparison study of torsional stress on bone.

Fractures that result from torsional loading of shafts in mechanical systems of nonbiologic materials generate a fracture line that forms a 45 degrees angle to an axis that is perpendicular to the direction of torsional loading on the shaft. As tension and compression are applied to these isotropic substances, the angle of fracture increases and decreases, respectively. Understanding how these forces, particularly compressive forces, generate elongation of a spiral fracture increases the ability to predict the extent of injury to bone. Fibular and metatarsal fractures are of primary importance to the podiatric physician, but any spiral fracture may be subject to torsional loading. Thus the principles stated here apply to the entire skeletal system. The purpose of this article is to provide a better understanding of the mechanics behind the causes and characteristics of fractures and to explore whether these same factors apply to the fracture mechanics of bone.

Animals↗

The novel kinase peptidylglycine alpha-amidating monooxygenase cytosolic interactor protein 2 interacts with the cytosolic routing determinants of the peptide processing enzyme peptidylglycine alpha-amidating monooxygenase.

The cytosolic domain of the peptide-processing integral membrane protein peptidylglycine alpha-amidating monooxygenase (PAM; EC 1.14. 17.3) contains multiple signals determining its subcellular localization. Three PAM cytosolic interactor proteins (P-CIPs) were identified using the yeast two hybrid system (Alam, M. R., Caldwel, B. D., Johnson, R. C., Darlington, D. N., Mains, R. E., and Eipper, B. A. (1996) J. Biol. Chem. 271, 28636-28640); the partial amino acid sequence of P-CIP2 suggested that it was a protein kinase. In situ hybridization and immunocytochemistry show that P-CIP2 is expressed widely throughout the brain; PAM and P-CIP2 are expressed in the same neurons. Based on subcellular fractionation, the 47-kDa P-CIP2 protein is mostly cytosolic. P-CIP2 is a highly selective kinase, phosphorylating the cytosolic domain of PAM, but not the corresponding region of furin or carboxypeptidase D. Although P-CIP2 interacts with stathmin, it does not phosphorylate stathmin. Site-directed mutagenesis, phosphoamino acid analysis, and use of synthetic peptides demonstrate that PAM-Ser(949) is the major site phosphorylated by P-CIP2. Based on both in vitro binding experiments and co-immunoprecipitation from cell extracts, P-CIP2 interacts with PAM proteins containing the wild type cytosolic domain, but not with mutant forms of PAM whose trafficking is disrupted. P-CIP2, through its highly selective phosphorylation of a key site in the cytosolic domain of PAM, appears to play a critical role in the trafficking of this protein.

Amino Acid Sequence↗

The risk of tetanus in podiatric medicine.

Although tetanus is a preventable disease, several cases are reported to the Centers for Disease Control and Prevention each year. Many conditions treated by podiatric physicians carry the risk of infection by Clostridium tetani, and it is advisable for podiatrists to update a patient's tetanus immunization status if the patient presents with a tetanus-prone wound.

Adult↗

Novel proteins that interact with the COOH-terminal cytosolic routing determinants of an integral membrane peptide-processing enzyme.

The steady state distribution of membrane forms of peptidylglycine alpha-amidating monooxygenase (PAM) in the secretory pathway of neurons and endocrine cells depends on signals in its cytosolic COOH-terminal domain (CD). Mutagenesis studies yielded catalytically active PAM proteins that are not properly localized or internalized. Employing the yeast two-hybrid system, we isolated two distinct cDNAs whose protein products showed a strong interaction with the CD of PAM. The interaction of these novel PAM COOH-terminal interactor proteins (P-CIPs) did not occur with a misrouted CD mutant as bait in the yeast system. Both proteins, P-CIP2 and P-CIP10, were expressed as fusion proteins that interacted in vitro with solubilized integral membrane PAM. P-CIP2 was homologous to several serine/threonine and dual specificity protein kinases, while P-CIP10 contained spectrin-like repeats. Endogenous P-CIP2 was localized to the Golgi region of AtT-20 corticotrope tumor cells, and expression of integral membrane PAM disrupted the distribution of endogenous P-CIP2. Both P-CIP2 and P-CIP10 mRNAs were found to be expressed in rat brain neurons also expressing PAM proteins. P-CIP2 and P-CIP10 may be members of a family of cytosolic proteins involved in the routing of membrane proteins that function in the regulated secretory pathway.

Amino Acid Sequence↗

Genetics of split hand and split foot. A case study.

Split hand and split foot is an autosomal dominant disorder that displays several genetic phenomena. These include variable expressivity, reduced penetrance, and segregation distortion. Although not fully understood at the molecular level, all are important in determining transmission of the gene thought to be mapped to the long arm of chromosome 7 (7q21.3-q22.1). These phenomena, therefore, have significant implications for inheritance of split hand and split foot and for proper referral for genetic counseling.

Chromosome Aberrations↗

Microembolization from atheroembolic disease or aneurysm. A case study.

Cyanosis of the digits may have several etiologies ranging from trauma to connective tissue disease; however, the most common cause of the so-called blue toe syndrome is atheroembolic disease or aneurysm and is frequently misdiagnosed on initial presentation. Pedal pulses are often palpable which may misdirect the physician from a diagnosis of vascular pathology. Furthermore, the proximal source of embolic shower may be far from the sight of symptoms. Noninvasive vascular testing, peripheral angiography, abdominal and popliteal ultrasonography, and echocardiography are all techniques that may be beneficial in discovering the origin of emboli. Atheroembolisms and aneurysms can be limb-threatening or life-threatening and hence early diagnosis is imperative.

Adult↗

Hand-foot-and-mouth disease.

Hand-foot-and-mouth disease is a highly contagious disease most often seen in children during the summer. It is caused most commonly by the virus coxsackie A16, but other enteroviruses have been implicated. It presents with low grade fever, and a vesicular eruption on the hands, feet, and mouth. More serious manifestations are seen less commonly. Diagnosis is most often clinical and treatment is symptomatic in nature. The infection in a male adult is presented.

Child, Preschool↗

Kaposi's sarcoma versus bacillary angiomatosis.

Persons with acquired immune deficiency syndrome (AIDS) are subject to a host of pathologic entities secondary to a depressed immune system. Kaposi's sarcoma frequently presents in this immunocompromised population and, therefore, diagnosis seems clinically straightforward. However, because of the prevalence of a strikingly similar infectious disease known as bacillary angiomatosis, skin biopsy of one or more lesions is crucial.

AIDS-Related Opportunistic Infections↗