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Biomedical subjects

B Clark

Publications and source records attributed to B Clark.

At least 73 records · Page 4Linked to original sources
PubMed1992

Striatal monoamine neurotransmitters and metabolites in dominantly inherited olivopontocerebellar atrophy.

We measured the levels of the monoamine neurotransmitters and metabolites in striatum of 14 patients with end-stage dominantly inherited olivopontocerebellar atrophy (OPCA). On average, dopamine levels were reduced in putamen (-53%), caudate (-35%), and nucleus accumbens (-31%). However, individual patient values showed a wide variation, indicating that mild to moderate striatal dopamine loss is a common but not constant feature of OPCA. Seven patients had marked putamen dopamine loss (-62% to -81%) but without evidence of correspondingly severe substantia nigra cell damage; this suggests the possibility of a "dying-back" phenomenon in which nerve terminal loss precedes cell body degeneration. Severe substantia nigra cell loss with almost total (-95% to -99%) putamen and caudate dopamine depletion was present in two patients; however, none of the 14 patients had had a clinical diagnosis of parkinsonism or was receiving antiparkinsonian medication. Mean striatal serotonin levels were normal, whereas concentrations of the serotonin metabolite 5-hydroxyindoleacetic acid were elevated by 47% to 63%; this suggests increased activity of raphe dorsalis serotonin neurons innervating the striatum, which might aggravate the functional consequences of the dopamine deficit.

Biogenic Amines↗
PubMed1992

Transmitter-operated channels in rabbit retinal astrocytes studied in situ by whole-cell patch clamping.

Glutamate and GABA open ion channels in the membranes of astrocytes found on the vitreal surface of the rabbit retinal visual streak. The glutamate-operated channels are opened by kainate, quisqualate, and AMPA, but not by NMDA, aspartate, or the metabotropic agonist 1-aminocyclopentane-1 S,3R-dicarboxylic acid. The effects of glutamate and its analogs can be blocked by 20 microM 6-cyano-7-nitroquinoxaline-2,3-dione. The conductance increase evoked by 10 microM glutamate, a concentration of this transmitter near to that found in the vitreous humor that bathes these cells, was equivalent to 22% of the cell's resting conductance. The conductance increase evoked by 1 microM GABA, a concentration near that found in the vitreous, was equivalent to 131% of the cell's resting conductance. The effects of GABA can be blocked by bicuculline. These data show that GABA, and non-NMDA-type glutamate receptors play an important part in determining the resting potential of visual streak astrocytes in situ and that these channels may be of general importance for the functions of astrocytes in vivo.

Animals↗
PubMed1991

Congenital ossifying fibroma (osteofibrous dysplasia) of the tibia--a case report.

Ossifying fibromas of the long bones of the leg are benign lesions occurring in the pediatric age group identical in histological appearance to the similarly named tumor of the jaw in adults. Most frequently presentation occurs after minor trauma with symptoms of a swelling of the tibia or fibula which may be painful. Pathological fracture or limp are also occasional presentations. Congenital cases are extremely rare. We describe an otherwise normal male neonate who presented at birth with a bowed right lower leg. The limb was 1 cm shorter than the other side, with tibia vara and a firm mass situated anteriorly. X-ray showed a mixed lytic and sclerotic lesion in the proximal metaphysis of the tibia. Biopsy showed collagenous stroma containing spindle cells and irregular trabeculae of woven bone rimmed by plump osteoblasts. As the appearances were typical of an ossifying fibroma (osteofibrous dysplasia) no surgical treatment was given. The patient was well with no growth of the tumor and with radiological evidence of healing at 1 year follow up. This case is presented to draw attention to the clinicopathological features of this unusual lesion which must be considered in the differential diagnosis of congenital lesions of the tibia.

Bone Neoplasms↗
PubMed1991

Comparison of clinical, radionuclide, and radiographic features of osteoarthritis of the hands.

Simultaneous clinical, scintigraphic, and macroradiographic assessments were carried out on 32 patients with hand osteoarthritis and the results at entry and one year reported. The presence and growth of osteophyte correlated with symptoms and a positive scan. The scan did not detect the radiographic features of juxta-articular radiolucencies, subchondral sclerosis, or cartilage thinning. Osteophytes, particularly when fast growing, produce pain, a 'hot' scan, and may predict disintegration of joint architecture.

Arthrography↗
PubMed1991

Sequences of taxol and cisplatin: a phase I and pharmacologic study.

Untreated and minimally pretreated solid tumor patients received alternating sequences of taxol and cisplatin. Sequential dose escalation of each agent using taxol doses of 110 or 135 mg/m2 and cisplatin doses of 50 or 75 mg/m2 resulted in four dosage permutations that induced grades 3 and 4 neutropenia in 72% to 84% and 50% to 53% of courses, respectively. Neutropenia was brief, and hospitalization for neutropenia and fever was required in 13% to 24% of courses. However, further escalation of taxol to 170 or 200 mg/m2 induced grade 4 neutropenia in 79% to 82% of courses. At the highest taxol-cisplatin dose level (200 mg/m2 to 75 mg/m2), the mean neutrophil count nadir was 98/microL, and hospitalization for neutropenia and fever was required in 64% of courses. The sequence of cisplatin before taxol, which has less antitumor activity in vitro, induced more profound neutropenia than the alternate sequence. Pharmacologic studies indicated that this difference was probably due to 25% lower taxol clearance rates when cisplatin preceded taxol. Although neurotoxicity was initially thought to be a potentially serious effect of the combination, mild to modest neurotoxicity occurred in only 27% of patients. Adverse effects also included myalgias, alopecia, vomiting, diarrhea, bradycardia, and asymptomatic ventricular tachycardia. Objective responses were noted in melanoma, as well as non-small-cell lung, ovarian, breast, head and neck, colon, and pancreatic carcinomas. Based on these results, the sequence of taxol before cisplatin at doses of 135 and 75 mg/m2, respectively, is recommended for phase II/III trials, with escalation of taxol to 170 mg/m2 if treatment is well tolerated.

Adult↗
PubMed1991

Mentors and role models for women in academic medicine.

Senior mentors and role models have a positive influence on the career advancement of junior professionals in law, business, and medicine. In medicine an increasing number of women are pursuing academic careers, but available senior mentors to provide career guidance are often lacking. We report on the results of a national survey of 558 full-time faculty women, aged 50 years and younger, in departments of medicine in the United States, regarding their experience with role models and mentors. Women with mentors report more publications and more time spent on research activity than those without mentors. Women with a role model reported higher overall career satisfaction. This report, with illustrative examples, may be helpful to other women pursuing academic careers and to physicians who serve as mentors or role models to others.

Data Collection↗
PubMed1991

Toward a rational therapeutic strategy for arachnoiditis. A possible role for d-penicillamine.

Twenty-six patients (13 men and 13 women), ranging in age from 38 to 75 years, with surgical and/or radiculographic evidence of chronic adhesive spinal arachnoiditis (CASA) were admitted to a randomly allocated, double-blind, 6-month crossover trial of d-penicillamine (500 mg/day) versus matching placebo. Assessments using subjective and objective criteria at 3-month intervals demonstrated no statistically significant effect with either d-penicillamine or placebo or between them. Thirteen of the 17 patients completing the trial expressed no clear preference. One patient preferred placebo. The remaining three patients who expressed strong preference for d-penicillamine (supported by objective data) subsequently maintained improvement on long-term therapy for up to 5 years. It is concluded that there may be a small subgroup of patients with CASA who might benefit from d-penicillamine therapy.

Adult↗
PubMed1990

Quantitative microfocal radiographic assessment of progression in osteoarthritis of the hand.

We studied 32 patients with osteoarthritis who had 5x macroradiographs taken of their wrists and hands at 6-month intervals over an 18-month period. The higher magnification and resolution of microfocal radiography permitted the quantitative detection of progressive changes in 4 different features: subchondral sclerosis, the number and size of osteophytes, juxtaarticular radiolucencies, and joint space narrowing. Compared with normal control subjects, subchondral cortical thickness was greater in all patients at entry and showed a variable degree of change over the study period. Osteophytes and juxtaarticular radiolucencies were present in all patients at study entry; by the end of the study, osteophytes had increased in number and area, and juxtaarticular radiolucencies had increased in area, but not in number. At entry, 44% of the patients had joint space narrowing significantly greater than that in the control subjects; by 18 months, this proportion increased to 65%. No correlation was found between subchondral sclerosis, osteophytes, juxtaarticular radiolucencies, and joint space narrowing. We conclude that in osteoarthritis of the hand, the bony changes have progressed significantly before the occurrence of radiographically evident joint space narrowing indicative of cartilage thinning.

Aged↗
PubMed1990

Differential binding of P. aeruginosa and S. aureus to corneal epithelium in culture.

Adherence of bacteria to corneal epithelium is a prerequisite for corneal infection. We used two methods to study the binding of Pseudomonas aeruginosa and Staphylococcus aureus to rabbit corneal epithelial cells in culture. In the first method, rabbit corneal epithelial cells grown on glass slides were incubated with P. aeruginosa or S. aureus (10(7) CFU/ml) at room temperature for 90 min, and the bacterial binding to the epithelial cells was examined by light microscopy. Both P. aeruginosa and S. aureus bound to epithelial cells. P. aeruginosa was bound to the cell periphery whereas S. aureus was bound randomly to the cell surface. In the second method, suspension cultures of corneal epithelial cells were used. In contrast to the findings in cultures on slides, binding pattern with cells in suspension was similar for both species and resembled that for S. aureus in cultures on slides. A much greater number of P. aeruginosa (186 +/- 11 bacteria/epithelial cell) than S. aureus (30 +/- 1.5 bacteria/epithelial cell) bound to epithelial cells grown on glass slides. In contrast, a similar number of P. aeruginosa (25 +/- 5.1) and S. aureus (20 +/- 4.7) bound to epithelial cells grown in suspension cultures. Using either method, Escherichia coli and Streptococcus pyogenes did not bind significantly (less than 5/cell) to corneal epithelial cells. The above methods should prove useful for characterization of bacterial binding to corneal epithelial cells in culture.

Animals↗
PubMed1989

Biological function of the rotavirus protein VP4: observations on porcine isolates from China.

Rotaviruses isolated from pigs in China were grown in MA104 cells. One tissue-culture-adapted isolate consisted of two subpopulations (variants), the RNA profiles of which differed in the relative migration of RNA segment 4 only. The variants were separated by plaque purification and by recovery from limiting dilutions and remained genetically stable. The variant possessing the slower migrating RNA segment 4, called 4S, grew faster and formed large plaques after 4-6 days incubation, whereas the variant possessing the faster migrating RNA segment 4, called 4F, grew more slowly and formed only microscopic plaques after 10-14 days incubation. The protein product of the 4F RNA occurred in much lower concentration in infected cells than the product of the 4S RNA. The RNA segments 4 of the two variants were found to be closely related when tested by dot hybridization under stringent conditions. The 4S RNA is more resistant to denaturation with methyl mercuric hydroxide than is the 4F RNA. The relevance of these findings to the biological functions of rotaviruses is discussed.

Animals↗
PubMed1989

Gene UL11 of herpes simplex virus type 1 encodes a virion protein which is myristylated.

We have investigated whether herpes simplex virus (HSV) contains structural polypeptides which are modified by myristic acid. We demonstrate that herpes simplex virions contain a family of myristylated proteins, Mr approximately 13,000 to 16,000. These were mapped, using HSV-1/HSV-2 intertypic recombinants, to 0.130 to 0.204 map units on the virus genome. Using anti-peptide sera, raised against the carboxyterminus of the predicted UL11 gene product, we have established that the myristylated virion polypeptides are products of the viral gene UL11.

DNA, Viral↗
PubMed1989

Clinicopathological and radiological features of two cases of intraventricular meningioma in childhood.

The clinical, radiological and pathological features of two cases of intraventricular meningioma in a 9-year-old boy and a 9-year-old girl are reported. Presenting features included headache, vomiting and somnolence with no localizing neurological signs on physical examination. Neither patient showed evidence of neurofibromatosis. CT scans were helpful in establishing the preoperative diagnoses with uniformly hyperdense, well-circumscribed lesions showing bright enhancement after contrast within the lateral and third ventricles respectively. Histological examination revealed mixed fibroblastic/angioblastic and fibroblastic patterns, with typical electron-microscopic and immunohistochemical features of meningioma. Successful surgical removal was achieved in both cases.

Cerebral Angiography↗
PubMed1989

HLA serologic epitopes.

A total of 25,000 antisera from parous women was evaluated for antibody specificity toward HLA epitopes in the A,B, and C loci. It was determined that most of the reactivity patterns against a large panel could be accounted for by the amino acid substitutions at the known residues. It has been surprising that each of the variable amino acids at each residue against which antisera have been found belonged on either the A, B, or C locus.

Amino Acid Sequence↗
PubMed1989

Overview and epitope matching.

1. Kidney graft survival rates have stabilized over the past 4 years, suggesting that gains achieved with CsA have plateaued. The overall 1-year graft survival is 77% for first cadaver donor transplants, 90% for parental donors, and 93% for HLA-identical sibling donors. Patient survival for all categories is now over 95%. 2. The UNOS 6-antigen match program has resulted in outstanding graft survivals. Of 88 kidneys which were transplanted into first graft recipients, the 6-antigen match kidney had a 1-year graft survival of 91% compared to 74% for the contralateral kidney transplanted locally (p less than 0.008). 3. In highly sensitized patients with more than 80% PRA the shipped 6-antigen matched kidney had a 91% 1-year graft survival rate compared to 72% survival in comparable control patients from the registry (p less than 0.005). In patients with less than 80% PRA, 6-antigen matched kidneys had 90% 1-year graft survival compared to 80% in controls (p less than 0.00001). 4. The spread of 1-year graft survival rates at 68 centers that performed more than 100 transplants was 63-94%. The cumulative graft survival of 6-antigen matches performed at 129 different centers was 90%. Thus, the strong center effect was neutralized by the use of matched transplants. 5. In contrast to the 1% of patients who would receive O-B,DR mismatched transplants on a random basis, if kidneys were shared in the national pool, 74% could receive such a transplant. We therefore propose that a keep one-share one policy be adopted for all kidneys harvested in the United States. If no 0-B,DR mismatched patient is available, both kidneys will be kept by the harvesting center. Since 63% of kidneys are currently being shared with other centers for various reasons, the 75% sharing suggested by the new system should not impose a hardship on transplant centers. The UNOS payback agreement will be replaced by this agreement by which shipping will be done only to achieve excellent matches. 6. In order to achieve a better method of excluding the worst mismatches, an attempt was made to develop a new method of mismatching using amino acid sequences of the HLA specificities. Donor and recipient types can be converted to amino acid sequences and the mismatching done on the basis of amino acids of mismatch at each residue or position. For each residue, specific combinations of amino acid substitutions were examined individually to determine their effect on graft survival. From these studies, a list of "immunogenic" amino acids was prepared, and graft survival was then computed for increasing numbers of amino acids of mismatch.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1989

Protein-related abnormalities in keratoconus.

Two-dimensional electrophoretic maps of extracts from eleven normal and eleven keratoconus corneas were compared. Of the eleven corneas analyzed, eight were pooled and the remaining three were analyzed individually. Several differences were demonstrated between electrophoretic patterns of normal and keratoconus corneas. In keratoconus corneas, 1) two abnormal components (MW 54kD and 26kD) were observed; 2) three normal corneal components (MW 12kD, 14kD, and 39kD) were present in significantly higher amounts; and 3) three normal corneal proteins (MW 66kD, 55kD, and 13kD) were present in reduced amounts. The molecular weight and isoelectric point of one of the normal corneal proteins that we found to be reduced in keratoconus corneas were close to that of a subunit of prolyl-4-hydroxylase, an enzyme required for hydroxylation of proline residues of collagen. The possibility the abnormal proteins detected in the keratoconus corneas were derived from those normal corneal proteins which were absent or were present in reduced amounts in the keratoconus corneas remains to be established. This study may provide protein markers for elucidation of the biochemical abnormality in keratoconus.

Adult↗