Biomedical subjects

K Harum

Publications and source records attributed to K Harum.

4 recordsLinked to original sources

PubMed2001

Sculpting the developing brain.

The developing brain experiences major construction during fetal life and for at least the first decade of childhood. Many more neurons and synoptic connections are produced than are needed for later function, and the mature brain is what remains after these excess building materials are "sculpted" away. This process is thought to be the basis for the developing brain's plasticity, or the capacity to adapt its behavior and circuitry to stimulation from the external environment. Plastic reorganization of the brain is now being studied in children and adults with new noninvasive tools such as functional brain magnetic resonance imaging. This exploratory tool and other new clinical methods demonstrate how the brain's functional "maps" undergo major reorganization in response to early environmental changes. The neurobiology of brain reorganization during development is also being studied with use of new insights into the molecular mechanisms for activity-dependent neuronal plasticity. Clinical disorders such as lead poisoning, metabolic and epileptic encephalopathies, and psychosocial deprivation may arise from disrupted brain plasticity. Several mental retardation syndromes and cognitive disorders recently recognized as being secondary to genetic disruption of intracellular signaling cascades may also disrupt this process. Understanding how the brain's circuitry is sculpted during development provides an important perspective for thinking about neurodevelopmental disorders.

Brain↗

PubMed1998

Inherited duplication Xq27-qter at Xp22.3 in severely affected males: molecular cytogenetic evaluation and clinical description in three unrelated families.

We describe the clinical phenotype in four males from three families with duplication (X)(qter-->q27::p22.3-->qter). This is an unusual duplication of the distal long arm segment, Xq27-qter, onto the distal short arm of the X chromosome at Xp22.3, as shown by fluorescent in situ hybridization analysis with multiple X-specific probes. The patients are young male offspring of three unrelated, phenotypically normal carrier women. The affected males have similar clinical manifestations including severe growth retardation and developmental delay, severe axial hypotonia, and minor anomalies. Such clinical similarity in three unrelated families demonstrates that this chromosome abnormality results in a new and distinct clinical phenotype. Replication studies, performed on two of the mothers, provided evidence that inactivation of the abnormal X chromosome permitted the structural abnormality to persist in these families for a generation or more in females without phenotypic expression.

Adult↗

PubMed1997

Cryptic terminal rearrangement of chromosome 22q13.32 detected by FISH in two unrelated patients.

Two unrelated patients with cryptic subtelomeric deletions of 22q13.3 were identified using FISH with the commercially available Oncor probe, D22S39. Proband 1 was found to have a derivative chromosome 22 resulting from the unbalanced segregation of a t(1;22)(q44;q13.32) in her mother. Additional FISH analysis of proband 1 and her mother placed the breakpoint on chromosome 22 in this family proximal to D22S55 and D22S39 and distal to D22S45. We have mapped D22S39 to within 170 kb of D22S21 using pulsed field gel electrophoresis. D22S21 is genetically mapped between D22S55 and D22S45. These data indicate that the deletion in proband 1 is smaller than in eight of nine reported del(22)(q13.3) patients. Probands 1 and 2 share features of hypotonia, developmental delay, and expressive language delay, also seen in previously reported del(22)(q13.3) patients, although proband 1 appears to be more mildly affected. Proband 1 is also trisomic for the region 1q44-->qter. This very small duplication has been previously reported only once and the patient had idiopathic mental retardation. This is the first report where 22q13.3 terminal deletion patients have been identified through the use of FISH, and the first report of a deletion of this region occurring because of missegregation of a parental balanced cryptic translocation. We feel that investigation of the frequency of del(22)(q13.3) in the idiopathic mentally retarded population is warranted and may be aided by the ability to use a commercially available probe (D22S39), which is already currently in use in a large number of cytogenetic laboratories.

Adult↗

PubMed1993

Anatomic and biomechanical properties of human lumbar dura mater.

Determinants of dural defects subsequent to deliberate or accidental dural puncture include the equipment, techniques, and the inherent anatomic and biomechanical properties of dura mater. These properties were studied in specimens of human and canine lumbar dura mater in an attempt to delineate the structure of the tissue and to characterize its behavior in biomechanical terms. Human dura had a longitudinal orientation on gross appearance, and was confirmed microscopically to be composed of longitudinal lamella of collagen and elastin fibers. Longitudinal tensile strength and stiffness were greater than transverse tensile strength and stiffness, which is consistent with the dura's apparent anatomic structure and functional requirements. Additional biomechanical testing of the dura demonstrated the property of relaxation which is a characteristic of a viscoelastic material. Significant differences were observed between human and canine dural properties, suggesting limited value of this animal model. Integration of these observed anatomic and biomechanical properties of the lumbar dura provides a greater understanding of dural puncture and may explain previous and often confusing clinical and experimental findings.

Adolescent↗