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Biomedical subjects

J G McComb

Publications and source records attributed to J G McComb.

At least 73 records · Page 4Linked to original sources
PubMed1994

Evidence for transcapillary transport of reduced glutathione in vascular perfused guinea-pig brain.

Using a vascular brain perfusion model in the guinea-pig, the net uptake of [35S]-GSH by the brain was found to be linear and similar in various regions during 10 min perfusion. Dual labeled [35S and 3H] GSH taken up by the brain had the same isotope ratio as the injected stock whether or not gamma- glutamyl transferase was inhibited. Greater than 96% of brain uptake of [35S]-cysteine-labeled GSH and [3H]-glycine-labeled GSH were in intact form. Transcytosis of [35S]-GSH from lumen into brain parenchyma was demonstrated using a capillary depletion technique. Both GSH and GSH-monoethyl ester inhibited [35S]-GSH transport. Thus, we have demonstrated blood-brain barrier extraction of circulating GSH in a brain perfusion model, and the transcytosis of intact GSH into the brain parenchyma without breakdown.

Animals↗
PubMed1994

Nicotine downregulates alpha 2 isoform of Na,K-ATPase at the blood-brain barrier and brain in rats.

Effects of chronic nicotine treatment on the relative levels of expression of Na,K-ATPase alpha and beta subunit isoforms were determined in rat cerebral microvessels and capillary-depleted brain homogenates by Western blot analysis. Nicotine, 4.5 mg/kg/day, was administered s.c. by osmotic mini-pumps for 14 days. Expression of alpha 2 isoform in microvessels and brains of nicotine-treated rats was reduced to 0.26 and 0.58 of control levels, respectively. Expression of alpha 1, alpha 3, beta 1 or beta 2 was unchanged. Nicotine decreased cerebromicrovascular and brain Na,ATPase enzymatic activities by 22% and 17%, respectively. It is suggested that chronic exposure to nicotine reduces expression of functional Na,K-ATPase at the blood-brain barrier and brain by downregulating the alpha 2 isoform.

Animals↗
PubMed1994

Blood-to-lens transport of reduced glutathione in an in situ perfused guinea-pig eye.

Transport mechanisms of reduced glutathione (GSH) in intact eye are poorly understood. In this study, an in situ vascular eye perfusion (VEP) model was used to characterize the transport kinetics of circulating GSH into the aqueous humor and lens in guinea pigs. Radiolabeled [35S]GSH or [3H]GSH and [14C]sucrose (an extracellular space marker) were exposed to the blood-aqueous barrier up to 10 min, and uptake of tracers by the aqueous humor and lens was determined in the presence of different concentrations of unlabeled peptide as GSH, a gamma-glutamyl compound as a derivative of GSH (GSH monoethyl ester), and an inhibitor of gamma-glutamyl transpeptidase (GGT) activity. Plasma-aqueous and aqueous-lens compartmental unidirectional transport constant, K(in), and the initial rapid volume of distribution, Vi, were estimated by multiple-time-point graphic analysis. Our results indicated that both labeled GSH and sucrose entered the aqueous humor slowly at comparable rates with respective blood-aqueous K(in) values of 1.34 +/- 0.12 and 1.25 +/- 0.08 min-1 x 10(3). In contrast to blood-aqueous transport, GSH uptake by the lens was rapid, and the respective aqueous-lens K(in) values for labeled GSH and sucrose were 79.3 +/- 4.1 and 3.5 +/- 0.7 min-1 x 10(3). Over 94% of plasma-derived GSH remained in its original molecular form of GSH in the lens, during the 10 min perfusion both with and without the GGT inhibitor, serine borate. The amount of [35S]GSH in lens anterior epithelium (dpm mg-1) was more than three times that of aqueous humor (dpm microliter-1) within only 10 min of VEP. There was also significant accumulation of [35S]GSH in the interior cortex, as indicated by 10-min cortex/aqueous ratio of 0.65. A specific GGT independent GSH transport system was demonstrated in the lens in situ, with a Km of 26 +/- 3 microM, and Vmax of 34 +/- 3 pmol min-1 g-1 of whole lens tissue water. The lenticular influx of GSH was inhibited by GSH monoethyl ester with an affinity that was half that for GSH. It is concluded that: (a) uptake of plasma-derived GSH into the aqueous humor is by simple diffusion, and (b) cellular uptake of GSH by the lens is carrier-mediated via mechanism that is separate from the transpeptidation metabolic pathway.

Animals↗
PubMed1994

Occipital reduction-biparietal widening technique for correction of sagittal synostosis.

In the older infant with a marked skull deformation from sagittal synostosis a midline craniectomy will not produce an optimal cosmetic result as the brain grows at a much reduced rate and cannot provide the impetus for passive correction of the deformity. An operative technique is described whereby the occipital prominence is reduced, the biparietal diameter widened, and the height of the calvarium lowered at the vertex. Although the frontal bossing is not directly addressed the changes in the remainder of the calvarium render the bossing of little cosmetic relevance and has not been a long-term problem in the group of patients treated with this technique. The amount of manipulation, operative time, and blood loss with the procedure is comparable to others reported. This technique does not have the potential to raise intracranial pressure if one takes care to avoid undue compression on the major dural venous sinuses. There have been no significant bony defects and no patient has required reoperation. The cosmetic results have been excellent.

Cephalometry↗
PubMed1994

Subcutaneous palisading granuloma of the scalp in childhood.

Subcutaneous palisading granulomas, lesions characterized by collagen necrosis and chronic inflammatory changes, may present as ill-defined, immobile, nontender masses of the scalp. They are frequently multiple and may vary in size over time. Imaging studies rarely show involvement of the calvarium. The histological pattern of palisading histiocytes around necrobiotic granulomas is seen in association with a variety of systemic illnesses but more commonly occurs as an isolated entity in childhood. They are unlikely to herald rheumatological disease unless the erythrocyte sedimentation rate is elevated. In the presence of juvenile rheumatoid arthritis, histological confirmation is usually not indicated. If the lesions are not associated with any other clinical symptoms excisional biopsy may be indicated to establish a diagnosis. The nodules need not be removed as they will spontaneously regress.

Child, Preschool↗
PubMed1994

The endoscopic stylet: technical notes.

The use of a small-diameter, rigid ventriculoscope as a stylet to place a catheter optimally within cerebrospinal fluid-containing spaces, is described.

Cerebrospinal Fluid Shunts↗
PubMed1994

Galactose-induced cataract formation in guinea pigs: morphologic changes and accumulation of galactitol.

PURPOSE: To develop and characterize a new model of galactose-induced cataract formation in young, 3- to 4-week-old Hartley guinea pigs. METHODS: Experimental animals were fed 50% galactose in powdered guinea pig chow containing 0.5 g ascorbate/kg diet. Control animals were fed normal powdered guinea pig chow (0.5 g ascorbate/kg diet). Lenses from all animals were subjected to photo-slit-lamp examination, light microscopic analysis, and high-pressure liquid chromatography (HPLC) analysis of polyol content. RESULTS: Photo-slit-lamp examination indicated initial opacities in equatorial subcapsular region between 3 and 5 days in all galactose-fed animals (20/20); opacities progressed toward the anterior pole when diet was extended to 14 days. Histologic analysis of the equatorial changes confirmed progressive cataract formation consisting of small intra-fibrillar vacuoles in the pre-equatorial region (3 days), an increased number of enlarged and coalesced vacuoles (6 days), and progressive tissue swellings with cellular disruption and signs of epithelial multilayering (14 days). The anterior epithelium showed increased cell height and swelling after 3 days of the galactose diet. HPLC analysis of lens tissue indicated progressive accumulation of galactitol, 18 mM after 3 days, which plateaued to about 30 mM between 6 and 14 days. The level of myo-inositol dropped from a control value of 2.8 +/- 0.7 mM to 1.5 +/- 0.7 mM after 3 days, and was nearly undetectable after 14 days of the galactose diet. CONCLUSIONS: The current study suggests that the guinea pig model may serve as a valuable new tool to study sugar-induced cataract formation and to characterize the early morphologic and biochemical events in cataractogenesis.

Animals↗
PubMed1993

Blood-brain barrier transport of circulating Alzheimer's amyloid beta.

The origin of amyloid beta (A beta) deposited in brain and cerebral blood vessels of patients with Alzheimer's Disease (AD) is not known. In this study, we tested whether soluble A beta (sA beta) can cross the blood-brain barrier (BBB). An in vivo vascular brain perfusion model and capillary depletion technique in guinea-pigs were used to determine cerebral capillary sequestration and blood-brain transport of a synthetic peptide identical with residues 1-40 (SP-40) of A beta. A saturable, specific binding of SP-40 has been demonstrated at the luminal side of the BBB, with the Kd of 25 +/- 2 nM, and Bmax of 188 +/- 11 fmol/min/g of isolated microvessels. A specific transcellular BBB transport of SP-40 into brain parenchyma exhibited the Km of 49 +/- 10 nM, and Vmax of 111 +/- 19 fmol/min/g of capillary depleted brain. We concluded that the BBB has the capability to control the cerebrovascular sequestration and blood-to-brain transport of circulating sA beta. Hence, sA beta can contribute to both cerebrovascular and parenchymal amyloid formation.

Amyloid beta-Peptides↗
PubMed1993

Differential expression of Na,K-ATPase alpha and beta subunit isoforms at the blood-brain barrier and the choroid plexus.

The relative levels of expression of Na,K-ATPase alpha and beta subunit isoforms were determined in rat cerebral microvessels, choroid plexus, and capillary-depleted brain homogenates by Western blot analysis. Three alpha (alpha 1, alpha 2, alpha 3) and two beta (beta 1, beta 2) subunits were detected in brain as previously reported. All 3 alpha and 2 beta isoforms were also found in microvessels. The choroid plexus expressed alpha 1, beta 1, and beta 2, while alpha 2 and alpha 3 were not found. Autoradiographic signals were normalized to a constant amount of protein from the 3 tissues to calculate relative levels of expression. Expression of alpha 1, alpha 2, and alpha 3 was higher in microvessels than in the brain, by 1.7-, 1.2-, and 1.2-fold, respectively, but expression of beta 1 and beta 2 was 5.5-fold lower. alpha 1 was 4-fold higher in the choroid plexus than in the brain, while expression of beta 1 and beta 2 was 15- and 5.5-fold lower, respectively. Na,K-ATPase enzymatic activities in microvessels and choroid plexus homogenates were similar and 5-fold lower than in brain homogenate. We conclude that: (a) expression of functionally active Na,K-ATPase isoenzymes in microvessels and choroid plexus is restricted in comparison to the brain possibly due to a limited pool of beta 1 and beta 2 subunits; (b) six structurally distinct Na,K-ATPase isoenzymes may be expressed in cerebral microvessels and two in the choroid plexus.

Animals↗
PubMed1993

Penetrating craniocerebral injury resultant from gunshot wounds: gang-related injury in children and adolescents.

We prospectively and retrospectively reviewed a series of 780 patients who presented to the University of Southern California/Los Angeles County Medical Center with a diagnosis of gunshot wound to the brain during an 8-year period. Of these, 105 were children ranging in age from 6 months to 17 years. Injuries were gang related in 76 (72%) children and adolescents. Stepwise linear regression analysis was used to formulate a predictive model of outcome in this population. Patient age (F = 10.92), sex (F = 9.32), occipital entry site (F = 8.17), bihemispheric injury (F = 8.50), and admission Glasgow Coma Scale (F = 69.91) were all found to correlate with outcome (P < 0.05). Significant differences between pediatric and adult populations were noted in transit time, entrance site, and age-related outcome. Occipital or assassination-type wounds were most common in children. In addition, a younger age was associated with poor outcome (P < 0.0001). We describe both the economic and racial trends in our population of patients in addition to weapon type and toxicological evaluation. The Department of Neurological Surgery is becoming directly involved in providing information to children at the junior high school level regarding gang activity and brain and spinal cord injury. In conjunction with the Community Youth Gang Services Organization and Think First Organization, we are attempting to integrate prevention through education and community mobilization. This is a plan aimed at informing and recovering the youth affected by gangs.

Adolescent↗
PubMed1992

Transport, uptake, and metabolism of blood-borne vasopressin by the blood-brain barrier.

Transport, binding, and metabolism of [phenylalanyl-3,4,5,-3H(N)]arginine vasopressin (AVP) by the blood-brain barrier (BBB) was studied in adult guinea-pigs by means of a novel vascular brain perfusion (VBP)/capillary depletion technique and HPLC. A time-dependent, progressive brain uptake of 3H-radioactivity was measured over the 10 min period of VBP both in brain homogenates and in brain tissue depleted of cerebral microvessels. The unidirectional blood-to-brain transport constant, K(IN), estimated by multiple-time tissue uptake analysis of the homogenate and postcapillary supernatant, indicated that the BBB transfer rate for [3H]AVP (K(IN) = 2.37 +/- 0.25 microliters min-1 per gram brain homogenate) was almost 10 times higher than for simultaneously perfused [14C]sucrose, a cerebrovascular space marker. In contrast to homogenate and postcapillary supernatant, the [3H]radioactivity determined in the vascular pellet after dextran density centrifugation of the brain homogenate was very low and only somewhat higher than for [14C]sucrose. HPLC analysis of the perfused brain tissue revealed time-dependent degradation of the blood-borne neuropeptide. The percentage of intact [3H]AVP as determined in the postcapillary supernatant progressively declined during brain perfusion, from 49% at 1 min to 11.9% at 10 min. The major detectable labeled metabolite was [3H]phenylalanine, the labeled amino acid residue of [3H]AVP. The aminopeptidase inhibitor bestatin (0.5 mM), perfused simultaneously with [3H]AVP by the VBP technique, did not alter tissue uptake of [3H]AVP, indicating that there was no significant hydrolysis of peptide by the luminal BBB surface.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

An in situ perfused guinea-pig eye model for blood-ocular transport studies: application to amino acids.

A technique for in situ vascular eye perfusion (VEP) in the guinea-pig has been developed for measurements of the blood-ocular transport kinetics of substrates under controlled conditions of arterial inflow. The blood-aqueous and blood-vitreous barriers remained intact to the vascular space marker [3H]dextran (MW 70 kDa) with the perfusion pressure maintained between 80 and 100 mmHg. Several 3H-, 14C- or 35S-labeled amino acids, and 3H- or 14C-labeled sucrose (extracellular space marker) were used to validate the VEP model for transport kinetic studies. Multiple time-point graphic analysis was used to estimate the compartmental unidirectional blood-ocular transport constants, K(in), within the 20 min period of the VEP experiment. Blood-to-aqueous humor K(in) values for [3H]serine, [14C]N-methyl-alpha-aminoisobutyric acid (MeAIB) and [3H] or ]14C]sucrose were 3.57 +/- 0.38, 1.21 +/- 0.13 and 1.13 +/- 0.17 microliters min-1 g-1, respectively. The respective blood-to-lens K(in) values for labeled serine, MeAIB and sucrose were 1.71 +/- 0.19, 0.09 +/- 0.03 and 0.03 +/- 0.002 microliters min-1 g-1. The uptake of newly secreted amino acids from the aqueous humor in the lens followed the order: [35S]methionine greater than [3H]serine greater than or equal to [35S]cysteine greater than or equal to [3H]alanine greater than [14C]cycloleucine greater than or equal to [14C]MeAIB greater than or equal to [3H] or [14C]sucrose. The data indicate lack of a rapid blood-to-lens uptake of two model amino acids defining the A and L amino acid carriers.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗
PubMed1992

Benign cerebellar astrocytomas of childhood.

Benign cerebellar astrocytomas of childhood are potentially surgically curable lesions. Histologically, these neoplasms can be divided into pilocytic and diffuse astrocytomas. Whether there is a difference in the recurrence rate between these two tumor types after a surgical resection is not clear. In addition, the role of immediate postoperative imaging in predicting a recurrence has not been established. To answer these questions, we have reviewed the charts of 23 patients with benign cerebellar astrocytomas treated at Childrens Hospital of Los Angeles over a 10-year period (1977-1987). Of the 23 tumors, 15 were pilocytic and 8 were diffuse. All patients underwent an attempted gross total surgical removal of the tumor, and all patients had a postoperative computed tomographic (CT) scan with and without intravenously administered contrast material performed within 72 hours of the operation. Based on the postoperative CT scan, 12 patients had residual tumors. Seven of the subtotally resected tumors were pilocytic (7 of 15), and 5 were diffuse (5 of 8). Interestingly, the surgeon believed that a gross total resection had been obtained in 9 of these patients. There have been 4 recurrences in these 23 patients, with a mean follow-up of 4.9 years. All recurrences were in patients with subtotal resections. Of the 11 patients with a total resection of the tumor, 7 developed a small rim of enhancement on subsequent scans an average of 5 months after the operation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

Management of symptomatic chronic extra-axial fluid collections in pediatric patients.

The records of 103 pediatric patients having symptomatic chronic extra-axial fluid collections treated at Children's Hospital of Los Angeles from 1977 to 1988 were reviewed. Patients were treated with observation, serial percutaneous needle drainage, drainage through burr holes, drainage into a closed external drainage system, or subdural to peritoneal shunt. If the initial treatment was not effective, additional forms of treatment were instituted. Shunts, ultimately used in 73% of the patients, proved to be the most effective treatment. Of the group with shunts, the extra-axial fluid was unilateral in 20% and bilateral in 80%. In those patients with bilateral effusions, no difference in efficacy of shunts was seen in patients treated with bilateral versus unilateral shunts. Of the 75 patients with shunts, 12% required a shunt revision for progressive or recurrent symptoms. Shunt infections occurred in 3% of the patients, necessitating removal of the shunt and treatment with antibiotics. Eosinophilia in the subdural fluid was associated with shunt obstruction requiring revision. The shunt was never removed in 51% of patients with no untoward effects. This study demonstrates that the most efficacious treatment of symptomatic chronic extra-axial fluid collections in children is a unilateral subdural to peritoneal shunt. The shunt need not be removed after resolution of the fluid collections.

Adolescent↗
PubMed1992

Spinal arachnoid cysts in the pediatric age group: an association with neural tube defects.

Between 1979 and 1991, spinal arachnoid cysts were found in 11 patients aged 19 months to 18 years (mean age 5 1/2 years). Of the 11 patients, six had a myelomeningocele and one diastematomyelia. The presenting symptoms included radicular pain (one patient), progressive weakness (three), increasing scoliosis (one), worsening spasticity (three), and recurrent urinary tract infections and progressive constipation (one). Two patients showed no symptoms from the spinal arachnoid cyst. The distribution of lesions was as follows: cervicomedullary (one patient), cervical (one), cervicothoracic (two), thoracic (four), lumbar (two), and sacral (one). Four of the 11 arachnoid cysts (all intradural) were located anterior to the spinal cord, three of which were in children with a myelomeningocele. Only two of the cysts were extradural; both were found in the lumbosacral region, and one was associated with diastematomyelia. Eight patients were treated with fenestration and/or resection of the cyst wall. Three patients with anterior cysts were treated with shunts, a cyst-to-pleural space shunt in two and a cyst-to-subarachnoid space shunt in one. All of the patients either improved or exhibited an arrest in the progression of their symptoms. Spinal arachnoid cysts are a treatable cause of progressive neurological deficits and, in this series, were frequently found in patients with neural tube defects.

Adolescent↗