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Biomedical subjects

A D Hofmann

Publications and source records attributed to A D Hofmann.

At least 19 recordsLinked to original sources

Xenopus embryonic spinal neurons express potassium channel Kvbeta subunits.

Developmental regulation of voltage-dependent delayed rectifier potassium current (I(Kv)) of Xenopus primary spinal neurons regulates the waveform of the action potential. I(Kv) undergoes a tripling in density and acceleration of it activation kinetics during the initial day of its appearance. Another voltage-dependent potassium current, the A current, is acquired during the subsequent day and contributes to further shortening of the impulse duration. To decipher the molecular mechanisms underlying this functional differentiation, we are identifying potassium channel genes expressed in the embryonic amphibian nervous system. Potassium channels consist of pore-forming (alpha) as well as auxiliary (beta) subunits. Here, we report the primary sequence, developmental localization, and functional properties of two Xenopus Kvbeta genes. On the basis of primary sequence, one of these (xKvbeta2) is highly conserved with Kvbeta2 genes identified in other species, whereas the other (xKvbeta4) appears to identify a new member of the Kvbeta family. Both are expressed in developing spinal neurons during the period of impulse maturation but in different neuronal populations. In a heterologous system, coexpression of xKvbeta subunits modulates properties of potassium current that are developmentally regulated in the endogenous I(Kv). Consistent with xKvbeta4's unique primary sequence, the repertoire of functional effects it has on coexpressed Kv1alpha subunits is novel. Taken together, the results implicate auxiliary subunits in regulation of potassium current function and action potential waveforms in subpopulations of embryonic primary spinal neurons.

Amino Acid Sequence↗

Overexpression of potassium channel RNA: in vivo development rescues neurons from suppression of morphological differentiation in vitro.

Neuronal differentiation often proceeds differently in vitro than it does in vivo. Previous work demonstrated that overexpression of potassium channel RNA reduces the number of morphologically identifiable neurons that appear in cultures prepared from neural plate stage (17-1/2 hr) embryos (Jones and Ribera, 1994). Here, we report that morphological differentiation of neurons in situ is only slightly affected by overexpression of potassium channels. Endogenous factors appear to compensate for the effect of channel overexpression. Consistent with this view, when cultures are prepared from older neural tube embryos (22-24 hr), more neurons containing excess potassium channel RNA differentiate morphologically in vitro. Exposure in situ to a rapid intracellular calcium chelator, but not to tetrodotoxin, omega-conotoxin or a slow calcium chelator, prevents the compensation provided by extended development in vivo. Typically, RNA overexpression is limited to half of the embryo in order to provide an internal control. However, when potassium channel RNA is overexpressed throughout the embryo, few neurons differentiate morphologically in vitro, even if cultures are prepared from older neural tube embryos. Thus, recovery is possible if a minimum of 5 hr of further development in vivo is allowed under conditions in which rapid elevations of intracellular calcium are permitted and half of the nervous system has normal levels of potassium channel RNA. These results suggest that different or additional mechanisms operate in situ than in vitro to promote morphological differentiation of neurons.

Animals↗

"Red herrings," adolescents, and testicular tumors.

Testicular tumors, although rare in the general population, comprise the most common class of solid tumors in males aged 15-34 years. Although commonly appearing as a painless scrotal mass, one-third of testicular tumor cases are accompanied by pain or other atypical symptoms that may confound diagnosis, particularly if the clinician is misdirected by other issues. In this case report of an adolescent male with embryonal cell carcinoma of the right testis, a premorbid history of psychological problems, and immature, complaining behavior led to an improper assessment of the significant clues in the patient's oral history and a delay in diagnosis.

Adolescent↗

Psychological factors in diabetes mellitus. A review of the literature with emphasis on adolescence.

In this thorough review of the literature of the past 100 years concerning psychological factors in diabetes mellitus, interpretation is channeled toward adolescence. In addition, emphasis is given to the major role that emotional components play in the development and maintenance of the brittle teenage diabetic. The integration of adolescent developmental issues of into physician treatment plans is stressed.

Adolescent↗

A perspective on the brittle teenage diabetic.

The brittle teenage diabetic presents a difficult problem well known to clinicians. It is the authors' contention that its major component is psychological and not biological, and that much of this poor control can be avoided by proper developmental planning from the onset of disease. Failure to modify transactional health care models appropriate for the child to that appropriate for the adolescent accounts for much of this difficulty. Anticipatory long-range planning is outlined to aid the physician in allowing the youth to isolate and insulate his diabetes from becoming either a focus for control contests and power struggles or a maladaptive, manipulative regressive behavior. The reasonable goal is to prevent any further hospitalizations for ketoacidosis or hypoglycemia beyond the first admission for diagnosis and initial stabilization. Five illustrative cases augment this discussion.

Adolescent↗

Chorioretinitis in the adolescent: two case presentations with discussion.

Two cases of chorioretinitis in adolescence demonstrate the characteristic course of events. It is typically caused by Toxoplasma gondii and is usually acquired congenitally. Toxocara infection must be considered in younger children. Other etiologic agents are rarely implicated in children and youth. Diagnosis of toxoplasmic chorioretinitis is based on a characteristic history of visual disturbance and specific funduscopic appearance, along with confirmatory serological studies. Management is complex, utilizing pyrimethamine (Daraprim), sulfadiazine, and prednisone in combination for several weeks or months. The combined long-term care by the physician generalist and ophthalmologist is essential. Recognition of adolescent developmental issues is important to insure optimal compliance. The prognosis is guarded, with 5% to 30% recurrence rates noted after treatment. Severe visual impairment may be seen.

Adolescent↗

The impact of illness in adolescence and coping behavior.

The emotional impact of serious illness or injury bears just as much potential for being disabling to an adolescent as does the condition itself. It is also these concerns and the possibilities for difficult behavior on the part of teenagers on the ward which frequently cause staff members to feel at a loss when caring for this reputedly difficult age group. But if one carefully examines the specific developmental stresses of illness and the various coping mechanisms by which the youth may counter them, a logical management approach emerges. To a large degree this approach depends on compensation, intellectualization, displacement and constructive denial but also recognizes that destructive denial, regression and projection do normally and naturally occur at various points in the course of illness and hospitalization and that panic and acting out may also readily occur, but less frequently. The deterence of the more deleterious responses and promotion of the more felicitious dependes on a ward setting which provides for the adolescent's growing need for independence and self-determination; for continued reassurance about body image integrity, for resumption of mastery and control; and for the maintenance or restoration of his sense of self-worth. These goals are achieved by encouraging the youth to be an active partner in his own care; to share in decisions made about his condition; to pursue just as much independent self-management as he can; to actively engage in establishing a peer group with other adolescents in the ward; to continue with his education, socialization, personal interests and outside peer contacts as much as possible; and to feel that the staff respects his dignity and privacy, likes him as a person and appreciates the courage and effort with which he is facing a difficult time.

Adolescent↗