Mechanism of action of Escherichia coli formamidopyrimidine N-glycosylase: role of K155 in substrate binding and product release.

Escherichia coli formamidopyrimidine N-glycosylase (fpg) is a DNA glycosylase with an associated beta,delta-lyase activity. We have recently shown that the highly conserved lysine residue K155 is important for base recognition. Incubation of a double-stranded DNA containing an abasic site with the wild-type fpg protein generated only beta,delta-product.

[Disk surgery--neurosurgery, orthopedic surgery or both?].

Bibliometric methods have been used to study the distribution of research literature on disc surgery between neurological and orthopaedic departments globally and within each of the Nordic countries. Worldwide, the total number of indexed papers was found to be almost twice as great for neurosurgical as for orthopedic institutions. Though figures for the Nordic countries were lower, they manifested the same trend, except those for Sweden where orthopaedic surgeons appear to do more research than neurosurgeons in this field.

Mechanism of action of base release by Escherichia coli Fpg protein: role of lysine 155 in catalysis.

Fpg protein (formamidopyrimidine/8-oxoguanine DNA N-glycosylase) is a DNA repair enzyme that catalyzes the removal of oxidized purines, most notably the mutagenic 7-hydro-8-oxoguanine (8oxoGua) lesion, by an N-glycosylase action. Additionally, Fpg protein catalyzes beta and delta elimination reactions subsequent to removal of the base lesions, as well as the analogous chemistry at abasic sites (AP sites). In this report, we show that of the two lysines that are conserved among the various putative prokaryotic Fpg proteins, a site specific alteration in one of them (lysine 155 changed to alanine) displays meaningful changes in substrate activities.

A common mechanism of action for the N-glycosylase activity of DNA N-glycosylase/AP lyases from E. coli and T4.

Duplex oligonucleotides containing the base lesion analogs, O-methylhydroxylamine- and O-benzylhydroxylamine-modified abasic (AP) sites, were substrates for the DNA N-glycosylases endonuclease III, formamidopyrimidine DNA N-glycosylase and T4 endonuclease V. These N-glycosylases are known to have associated AP lyase activities. In contrast, uracil DNA N-glycosylase, a simple N-glycosylase which does not have an associated AP lyase activity, was unable to recognize the modified AP sites.

Damage, repair, and mutagenesis in nuclear genes after mouse forebrain ischemia-reperfusion.

To determine whether oxidative stress after cerebral ischemia-reperfusion affects genetic stability in the brain, we studied mutagenesis after forebrain ischemia-reperfusion in Big Blue transgenic mice (male C57BL/6 strain) containing a reporter lacI gene, which allows detection of mutation frequency. The frequency of mutation in this reporter lacI gene increased from 1.5 to 7.

From ion currents to genomic analysis: recent advances in GABAA receptor research.

The gamma-aminobutyric acid type A (GABAA) receptor represents an elementary switching mechanism integral to the functioning of the central nervous system and a locus for the action of many mood- and emotion-altering agents such as benzodiazepines, barbiturates, steroids, and alcohol. Anxiety, sleep disorders, and convulsive disorders have been effectively treated with therapeutic agents that enhance the action of GABA at the GABAA receptor or increase the concentration of GABA in nervous tissue. The GABAA receptor is a multimeric membrane-spanning ligand-gated ion channel that admits chloride upon binding of the neurotransmitter GABA and is modulated by many endogenous and therapeutically important agents.

Does a routine operation for intracranial aneurysm incur brain damage?

A biochemical marker of brain cell damage, the BB-isozyme of the intracellular enzyme Creatine Kinase (CK), was used to evaluate any possible injury to the brain, caused by an operation for a ruptured intracranial aneurysm (SAH). CSF-CK BB was assessed before and at intervals after operation in a series of 60 patients, aged 29-71 (mean 51 years) operated on for intracranial aneurysms, all but one after SAH. The m/f ratio was 18/42.

Neurosurgical publications in European journals.

The number of papers published in European neurosurgical journals during the last decade (1980-90) was analysed using online databases. Thirteen journals devoted to neurosurgery were published in Europe at that time. In five of them neurosurgery appears together with other specialties.

Relation between sensory disturbance and outcome after retrogasserian glycerol rhizotomy.

The relation between postoperative sensory deterioration and surgical outcome in 54 patients treated by retrogasserian glycerol rhizotomy for trigeminal neuralgia was studied. The facial sensibility was assessed one day and three months postoperatively. Thresholds for perception and pain were determined quantitatively using transcutaneous electrical stimulation and clinically by light touch and pinprick tests.

Percutaneous stereotactic brain tumour biopsy and cyst aspiration with a non-invasive frame.

A non-invasive Stereoadapter was used for stereotactic CT-guided percutaneous brain biopsy in 18 patients with 16 solid tumours and four cysts. The Stereoadapter was mounted on the patient's head using ear plugs and a nasion support. After the CT study, the Stereoadapter was detached.

Relationship between CT attenuation changes and post-traumatic CSF-CKBB-activity after severe head injury in man.

In order to evaluate if it is practically possible to assess the volume of contused brain tissue from the CT pictures, a comparison has been carried out between the size of the cerebral contusion(s)--as estimated from the CT scans--and the post-traumatic CSF-CKBB activity, in a series of 29 patients with severe head injury. A clearance curve for the elimination of CKBB from the CSF was constructed. The relation between contusion volume and CSF-CKBB-activity was not statistically significant, while the relationships between contusion volume and outcome, and between CSF-CKBB, as estimated at 6 hours after from the clearance curve, and outcome, were.

The use of chordotomy to treat pain from gynecologic cancer.

Tumor growth in the pelvis with nerve involvement causes severe pain which is notoriously resistant to pharmacological treatment. Chordotomy is a classical method for the relief of pain. This is a retrospective study of 24 chordotomy cases, operated on at the department of Neurosurgery, and independently evaluated at the department of Gynecologic Oncology.

Nerve crush--a possible treatment of peripheral neuralgia.

Twenty-three patients with neuralgic pain (mean duration 3 years) were treated with crushing instead of sectioning the peripheral nerve. There was immediate relief of pain in 19 patients (83%). With the return of skin sensation the pain recurred after 3-4 months in 4 patients and within 2.

CKBB-enzyme activity in serum in neonates born after vaginal delivery and cesarean section.

Creatine kinaseBB has been analysed in blood from the umbilical cord and from venous blood within 24 hours after birth in infants without any signs of perinatal asphyxia. S-CKBB activity was found to be much higher than in adults and older children. 25% of the children born after normal vaginal delivery showed very high S-CKBB activities, higher than any of the children born by elective cesarean section.

Internal neurolysis or ligament division only in carpal tunnel syndrome. II. A 3 year follow-up with an evaluation of various neurophysiological parameters for diagnosis.

48 patients with clinical and neurophysiological signs of carpal tunnel syndrome were randomized to any of two operative methods: Internal neurolysis of the median nerve with a microsurgical technique, or simple division of the carpal ligament (flexor retinaculum). After a minimum follow-up period of 3 years 81% of the patients did not report any complaints at all, and all patients considered themselves improved after operation. There was no difference between the operation groups.

CSF brain creatine kinase levels and lactic acidosis in severe head injury.

The posttraumatic creatine kinase-BB isoenzyme (CKBB) activity and lactate concentration in ventricular cerebrospinal fluid (CSF) have been studied in 29 patients with severe head injuries. The CKBB activity reaches its maximum a few hours after trauma, and has a monoexponential drop with a half-time of approximately 10 hours. Ventricular CSF lactate concentration continues to rise in patients with a poor outcome, and decreases only slowly and inconsistently in most of the other patients.

DNA degradation by bleomycin: evidence for 2'R-proton abstraction and for C-O bond cleavage accompanying base propenal formation.

Reaction of poly(dA-[2'S-3H]dU) with activated bleomycin yields [3H]uracil propenal that completely retains the tritium label. In contrast, we have previously shown that reaction of poly(dA-[2'R-3H]dU) with activated bleomycin affords unlabeled uracil propenal [Wu, J. C.