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Biomedical subjects

L N Johnson

Publications and source records attributed to L N Johnson.

196 records · Page 11Linked to original sources
PubMedDate not supplied

The design of potential antidiabetic drugs: experimental investigation of a number of beta-D-glucose analogue inhibitors of glycogen phosphorylase.

alpha-D-glucose is a weak inhibitor (Ki = 1.7 mM) of glycogen phosphorylase (GP) and acts as physiological regulator of hepatic glycogen metabolism; it binds to GP at the catalytic site and stabilizes the inactive T state of the enzyme promoting the action of protein phosphatase 1 and stimulating glycogen synthase. The three-dimensional structures of T state rabbit muscle GPb and the GPb-alpha-D-glucose complex have been exploited in the design of better regulators of GP that could shift the balance between glycogen synthesis and glycogen degradation in favour of the former. Close examination of the catalytic site with alpha-D-glucose bound shows that there is an empty pocket adjacent to the beta-1-C position. beta-D-glucose is a poorer inhibitor (Ki = 7.4 mM) than alpha-D-glucose, but mutarotation has prevented the binding of beta-D-glucose in T state GP crystals. A series of beta-D-glucose analogues has been designed and tested in kinetic and crystallographic experiments. Several compounds have been discovered that have an increased affinity for GP than the parent compound.

Crystallography↗
PubMedDate not supplied

Ocular invasion in mucormycosis.

The histopathologic findings in a case of ocular invasion in rhinocerebral mucormycosis are described. The findings of hyphae in the inner sclera and marked involvement of the posterior ciliary arteries suggested an arterial route of ocular invasion by fungus. Only five other cases of rhinocerebral mucormycosis with ocular fungal invasion have been reported to our knowledge. All six patients died from the infection. As a group, these cases suggest that the presence of ocular infiltration by fungus may indicate poor prognosis in rhinocerebral mucormycosis.

Aneurysm, Infected↗
PubMedDate not supplied

Seizures and cortical blindness after meglumine (hypaque) administration: a variant of autonomic dysreflexia.

Autonomic dysreflexia (AD) is a syndrome that consists of facial flushing, excessive sweating, nasal congestion, throbbing headache and paroxysmal hypertension which may occur in response to bladder distension in patients with spinal cord lesions above the T6 level. We report the case of a C2 quadriplegic patient who developed clinical features of AD along with cortical blindness and seizures after administration of meglumine (Hypaque) for diagnostic cystogram.

Adult↗
PubMedDate not supplied

Millisecond X-ray diffraction and the first electron density map from Laue photographs of a protein crystal.

Attempts to use X-ray crystallography to extract three-dimensional information on transient phenomena in crystals have been hampered primarily by long data collection times. Here we report on the first difference Fourier map obtained from Laue diffraction photographs of a protein crystal, glycogen phosphorylase b. Data collection time was 3 s using the high-intensity white X-radiation generated on the wiggler magnet of the Daresbury Synchrotron Radiation Source (SRS), but data acquisition in the millisecond-submillisecond range is possible. The method presented here uses a simple difference technique and was designed to analyse structural changes relative to a known starting structure. The combination of this approach with cine techniques allows the recording of three-dimensional motion pictures at atomic resolution and opens up new areas in structural biology and chemistry.

Electrons↗