PubMed Health⌕ Search

Biomedical subjects

S P Johnson

Publications and source records attributed to S P Johnson.

At least 19 recordsLinked to original sources
PubMed2000

The role of good form in young Infants' perception of partly occluded objects.

Young infants have been reported to perceive the unity of a center-occluded object when the visible ends of the object undergo common motion, but not on the basis of stationary information (e.g., P. J. Kellman & E. S. Spelke, 1983). We investigated the possibility that 4-month-old infants will attend to and utilize the global configuration (i.e., the "good form") of a partly occluded, moving object to perceive its unity and coherence behind the occluder. In the first experiment, infants viewed a partly occluded circle or cross that translated laterally. Infants who habituated in the minimum number of trials ("fast habituators") showed a reliable posthabituation preference for a broken object over a complete object, indicating perception of unity in the habituation display. Slow habituators exhibited no posthabituation preference. In the second experiment, infants were presented with small ring and cross displays, and the infants looked longer at the broken object. There were no reliable differences in performance between fast and slow habituators. A control group demonstrated no reliable posthabituation preference. In three additional conditions, infants viewed either a partly occluded half ring or a display in which two rod parts were either relatable and nonaligned or nonrelatable. The results indicated that curvature per se provided information in support of completion, in addition to global configuration and motion. Implications for theories of infants' visual development are discussed.

Case-Control Studies↗
PubMed2000

Schedule-dependent activity of irinotecan plus BCNU against malignant glioma xenografts.

PURPOSE: To further evaluate the activity of irinotecan (CPT-11) plus 1,3-bis-(chloroethyl)-1-nitrosourea (BCNU) in the treatment of central nervous system tumor-derived xenografts in athymic nude mice. METHODS: We report studies evaluating the schedule-dependence of this regimen in the treatment of the malignant glioma xenograft D-54 MG. RESULTS: The combination of BCNU and CPT-11 showed the highest enhancement index (2.0-3.3) when BCNU was given on day 1 and CPT-11 was given on days 1-5 and 8-12. Delay of CPT-11 administration to day 3 or day 5 substantially decreased activity with enhancement indices of 1.6-1.8 and 0.6-1.0, respectively. Delay of BCNU administration to day 8 also reduced the CPT-11 activity with enhancement indices of 1.2-1.4. CONCLUSIONS: These results suggest that the presence of a BCNU-induced adduct or possibly crosslink prior to administration of CPT-11 is critical for enhanced activity. Although the mechanism of this enhancement is not currently known, a phase I trial of CPT-11 plus BCNU for adults with recurrent malignant glioma based on these results is in progress.

Animals↗
PubMed2000

Amoxicillin pharmacokinetics in harbor seals (Phoca vitulina) and northern elephant seals (Mirounga angustirostris) following single dose intravenous administration: implications for interspecific dose scaling.

The pharmacokinetics of sodium amoxicillin after a single intravenous dose of 20 mg/kg were determined in ten harbor seals (Phoca vitulina) and ten northern elephant seals (Mirounga angustirostris). The seals ranged in age from 1 to 6 months and the mean weights were 11.7 kg (range, 9.5-18.5 kg) for harbor seals and 47.1 kg (range, 39.5-61.4 kg) for elephant seals. The median half-life of amoxicillin (quartiles) in harbor seals, 1.5 (1.0-3.1) h. was not statistically different from that of elephant seals, 2.0 (1.4-3.8) h, nor were the differences between the terminal elimination rate constants between the two species. The only statistically significant differences between species were for area-under-the-curve (AUC), and total systemic clearance. The lack of statistical significance for differences in the volume of distribution at steady-state (Vss) may have been due to minor differences in the time frame of data collection and dose administered between the two groups. A true physiologic difference in drug handling, possibly related to renal perfusion or tubal secretory efficiency could affect amoxicillin kinetics in these species, and longer administration intervals may be appropriate for elephant seals as compared to harbor seals when administering multiple dose amoxicillin therapy at 20 mg/kg.

Amoxicillin↗
PubMed2000

Schedule-dependent activity of temozolomide plus CPT-11 against a human central nervous system tumor-derived xenograft.

Temozolomide, an imidazole tetrazinone, and CPT-11, a camptothecin derivative, have previously been shown to have anti-central nervous system tumor activity in laboratory and clinical studies. The current experiments were designed to evaluate the activity of temozolomide plus CPT-11 against a malignant glioma-derived xenograft, D-54 MG, growing s.c. in athymic nude mice. The initial schedule of i.p. drug administration was temozolomide at 0.1 LD10 on day 1 and CPT-11 at 0.1 LD10 on days 1-5 and 8-14. The combination of these two agents produced greater than additive activity against D-54 MG. This enhanced activity was maintained when the initial administration of CPT-11 was delayed to day 3 or day 5. However, when CPT-11 was administered first on day 1 using 0.5 LD10 (for the single dose schedule) followed by temozolomide (0.1 LD10) 5 h, 3 days, or 5 days later, the enhancement of activity was substantially reduced. These results demonstrate that the combination of temozolomide plus CPT-11 displays a schedule-dependent enhancement of antitumor activity, suggest a mechanistic explanation for the enhanced activity, and provide the rationale for a Phase I trial of this regimen.

Animals↗
PubMed2000

Infants' perception of transparency.

Four- and 7-month-old infants' perception of transparency was investigated with computer-generated achromatic or color displays depicting a semitransparent box occluding the center of a rod. Following habituation, infants viewed test displays consisting of either a two-color rod (corresponding to the habituation display's proximal characteristics) or a solid rod (corresponding to the distal characteristics of the event depicted by the habituation display). Looking-time results from 4-month-olds suggested perception of transparency in color displays but not in an achromatic display. An additional condition indicated that transparency perception may rely on the visibility of background texture through the transparent surface. Seven-month-olds, in contrast, provided some evidence of transparency perception in the achromatic display. Implications for the development of infants' responses to object properties and perceptual segregation are discussed.

Age Factors↗
PubMed1999

Synchronous change and perception of object unity: evidence from adults and infants.

Adults and infants display a robust ability to perceive the unity of a center-occluded object when the visible ends of the object undergo common motion (e.g. Kellman, P.J., Spelke, E.S., 1983. Perception of partly occluded objects in infancy. Cognitive Psychology 15, 483-524). Ecologically oriented accounts of this ability focus on the primary of motion in the perception of segregated objects, but Gestalt theory suggests a broader possibility: observers may perceive object unity by detecting patterns of synchronous change, of which common motion is a special case. We investigated this possibility with observations of adults and 4-month-old infants. Participants viewed a center-occluded object whose visible surfaces were either misaligned or aligned, stationary or moving, and unchanging or synchronously changing in color or brightness in various temporal patterns (e.g. flashing). Both alignment and common motion contributed to adults' perception of object unity, but synchronous color changes did not. For infants, motion was an important determinant of object unity, but other synchronous changes and edge alignment were not. When a stationary object with aligned edges underwent synchronous changes in color or brightness, infants showed high levels of attention to the object, but their perception of its unity appeared to be indeterminate. An inherent preference for fast over slow flash rates, and a novelty preference elicited by a change in rate, both indicated that infants detected the synchronous changes, although they failed to use them as information for object unity. These findings favor ecologically oriented accounts of object perception in which surface motion plays a privileged role.

Adult↗
PubMed1999

Multiple DNA repair mechanisms and alkylator resistance in the human medulloblastoma cell line D-283 Med (4-HCR).

PURPOSE: We have previously reported preferential repair of DNA interstrand crosslinks in the 4-hydroperoxycyclophosphamide-resistant human medulloblastoma cell line D-283 Med (4-HCR). We now report further studies that explored the potential mechanisms underlying this repair. METHODS: Limiting dilution assays and Western, Southern, and Northern blots were used to compare specific differences between D-283 Med (4-HCR) and its parental line D-283 Med. RESULTS: D-283 Med (4-HCR) was cross-resistant to melphalan and 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), with O6-alkylguanine-DNA alkyltransferase (AGT) levels of 466+/-164 fmol/mg protein; AGT levels in the parental line, D-283 Med, were 76+/-96 fmol/mg. The increase in AGT activity was not a result of gene amplification. Depleting AGT with O6-benzylguanine partially restored sensitivity to BCNU. Both cell lines were deficient in the human mismatch protein MutLalpha. ERCC4 mRNA and poly(ADP-ribose) polymerase levels were similar in both cell lines, and ERCC1 mRNA levels were 2- to 2.5-fold lower in D-283 Med (4-HCR). Topoisomerase I levels were 2- to 2.5-fold higher in D-283 Med compared with D-283 Med (4-HCR). CONCLUSION: These results, while illustrating the multiple differences between D-283 Med and D-283 Med (4-HCR), do not explain the enhanced DNA interstrand crosslink repair seen in D-283 Med (4-HCR).

Antineoplastic Agents, Alkylating↗
PubMed1999

Modulation of cyclophosphamide activity by O6-alkylguanine-DNA alkyltransferase.

PURPOSE: The human medulloblastoma cell line D283 Med (4-HCR), a line resistant to 4-hydroperoxycyclophosphamide (4-HC), displays enhanced repair of DNA interstrand crosslinks induced by phosphoramide mustard. D283 Med (4-HCR) cells are cross-resistant to 1,3-bis(2-chloroethyl)- -nitrosourea, but partial sensitivity is restored after elevated levels of O6-alkylguanine-DNA alkyltransferase (AGT) are depleted by O6-benzylguanine (O6-BG). Studies were conducted to define the activity of 4-HC and 4-hydroperoxydidechlorocyclophosphamide against D283 Med (4-HCR) after AGT is depleted by O6-BG. METHODS: Limiting dilution and xenograft studies were conducted to define the activity of 4-HC and 4-hydroperoxydidechlorocyclophosphamide with or without O6-BG. RESULTS: The activity of 4-HC and 4-hydroperoxydidechlorocyclophosphamide against D283 Med (4-HCR) was increased after AGT depletion by O6-BG preincubation. Similar studies with Chinese hamster ovary cells, with or without stable transfection with a plasmid expressing the human AGT protein, revealed that the AGT-expressing cells were significantly less sensitive to 4-HC and 4-hydroperoxydidechlorocyclophosphamide. Reaction of DNA with 4-HC, phosphoramide mustard, or acrolein revealed that only 4-HC and acrolein caused a decrease in AGT levels. CONCLUSIONS: We propose that a small but potentially significant part of the cellular toxicity of cyclophosphamide in these cells is due to acrolein, and that this toxicity is abrogated by removal of the acrolein adduct from DNA by AGT.

Animals↗
PubMed1998

Young infants' perception of illusory contours in dynamic displays.

Ninety-six 4-month-old infants were habituated to one of three computer-generated displays depicting two rod parts above and below an occluding box. In the first display, the surfaces and boundaries of the rod and box were specified by dense surface texture. Their depth segregation was specified by accretion and deletion of background texture and motion shear. In the second display, the unity of the rod parts and box, and their depth segregation, were specified only by illusory contours. In the third display, the boundaries of the rod and box were specified by illusory contours, perceptible only via spatiotemporal integration of accretion and deletion of sparse-background-texture elements. Infants appeared to perceive object unity, and segregate the rod and box surfaces, in all three displays, indicating use of illusory contours to perceive bounded surfaces in depth. The results suggest a cognitive contribution to perception of some illusory contours, abilities which seem to be present by at least 4 months of age.

Cognition↗
PubMed1998

Effect of anatomic distribution of pulmonary emboli on interobserver agreement in the interpretation of pulmonary angiography.

OBJECTIVE: This study examines the anatomic distribution of emboli on pulmonary angiography and attempts to determine the relationship of vessel size to interobserver agreement, two factors having important implications in comparing pulmonary angiography with cross-sectional imaging for pulmonary embolism. MATERIALS AND METHODS: One hundred twenty-five consecutive pulmonary angiograms were reviewed retrospectively by three interventional radiologists. Initial interpretations were recorded and compared to determine interobserver agreement on a per-patient and per-embolus basis. Discordant interpretations were reviewed by all radiologists for a consensus interpretation. RESULTS: Unanimous per-patient agreement occurred in 91% (114/125) of initial interpretations. The largest artery containing acute pulmonary embolism was segmental or larger in 24 patients (83% of patients with acute positive findings, 19% of all patients) and subsegmental in only five patients (17% and 4%, respectively). On a per-patient basis, initial interobserver agreement averaged 45% and unanimous consensus agreement was achieved for 79% of patients having isolated subsegmental pulmonary embolism. Consensus readings altered initial per-patient interpretations for 30% of patients having only subsegmental pulmonary embolism; per-embolus interpretations were altered for 37% of all subsegmental emboli. CONCLUSION: Subsegmental emboli occurring as isolated findings are relatively rare. Approximately one third of subsegmental emboli and one third of patients having isolated subsegmental emboli may be initially misdiagnosed on pulmonary angiography. Objections to cross-sectional imaging for pulmonary embolism based on the inability to detect subsegmental pulmonary embolism when compared with pulmonary angiography should be reexamined with this data in mind.

Angiography↗
PubMed1998

Causes of erroneous white blood cell counts and differentials in clinically healthy young northern elephant seals (Mirounga angustirostris).

From 1993 to 1995, approximately 10% of the clinically healthy northern elephant seals (Mirounga angustirostris) at The Marine Mammal Center in California exhibited a large unexplained increase in their white blood cell (WBC) count. In these animals, WBC counts ranged from 28,780 to 125,000/mm3, with a mean of 50,087/mm3. Significant correlations between the leukocytosis and weight gain and day of admittance were identified, but no correlation existed between leukocytosis and general state of health, sex, length of stay, or diet. Bone marrow contamination of blood samples, erroneous automated leukocyte counts, and leukogram changes consistent with subclinical inflammation were the major factors contributing to the elevated WBC counts in these apparently clinically healthy animals.

Animals↗
PubMed1998

Analysis of DNA mismatch repair proteins in human medulloblastoma.

During replication, the primary function of the eukaryotic DNA mismatch repair (MMR) system is to recognize and correct mismatched base pairs within the DNA helix. Deficiencies in MMR have been reported previously in cases of hereditary nonpolyposis colorectal cancer and sporadic tumors occurring in a variety of tissues including gliomas. Furthermore, recent evidence indicates that the MMR system may be involved in mediating therapeutic sensitivity to alkylating agents. In this study, 22 neoplastic tissue samples from 22 patients who underwent surgical resection for medulloblastoma, a common cerebellar tumor of childhood, were assayed for the presence or absence of MMR polypeptides using Western blot and immunohistochemical techniques. Results from these experiments indicate that the MMR system is not commonly deficient in medulloblastoma.

Adaptor Proteins, Signal Transducing↗
PubMed1998

Antimicrobial susceptibility of bacteria isolated from pinnipeds stranded in central and northern California.

Over a 2-yr period (1994-1995), the antimicrobial susceptibilities of 129 bacterial isolates recovered from live stranded California sea lions (Zalophus californianus), harbor seals (Phoca vitulina), and northern elephant seals (Mirounga angustirostris) were studied. Nineteen genera of bacteria were isolated from various sites of inflammation; abscesses and umbilici were the most common sites. Seventy-two percent of the bacterial isolated were gram negative, and the Enterobacteriaceae (Escherichia coli, Proteus spp., Klebsiella spp., Salmonella spp.) accounted for 75% of the gram-negative isolates. All of the gram-positive isolates were either Enterococcus spp. or Staphylococcus aureus. Multiple drug resistance was present in all but one of the bacterial isolates. The gram-positive bacteria were most susceptible to amoxicillin-clavulanic acid (77% of 36 isolates) and least susceptible to lincomycin (18% of 11 isolates). The gram-negative bacteria were most susceptible to amikacin (91% of 91 isolates) and least susceptible to clindamycin (3% of 109 isolates).

Abscess↗
PubMed1997

Methylator resistance mediated by mismatch repair deficiency in a glioblastoma multiforme xenograft.

A methylator-resistant human glioblastoma multiforme xenograft, D-245 MG (PR), in athymic nude mice was established by serially treating the parent xenograft D-245 MG with procarbazine. D-245 MG xenografts were sensitive to procarbazine, temozolomide, N-methyl-N-nitrosourea, 1,3-bis(2-chloroethyl)-1-nitrosourea, 9-aminocamptothecin, topotecan, CPT-11, cyclophosphamide, and busulfan. D-245 MG (PR) xenografts were resistant to procarbazine, temozolomide, N-methyl-N-nitrosourea, and busulfan, but they were sensitive to the other agents. Both D-245 MG and D-245 MG (PR) xenografts displayed no O6-alkylguanine-DNA alkyltransferase activity, and their levels of glutathione and glutathione-S-transferase were similar. D-245 MG xenografts expressed the human mismatch repair proteins hMSH2 and hMLH1, whereas D-245 MG (PR) expressed hMLH1 but not hMSH2.

Animals↗
PubMed1997

Stent deformation and intimal hyperplasia complicating treatment of a post-carotid endarterectomy intimal flap with a Palmaz stent.

We report a case of common carotid artery Palmaz stent placement for treatment of an intimal flap after surgical endarterectomy. Despite technical success with an excellent immediate result, a significant stenosis detected by duplex sonographic examination developed at 10 months. This stenosis, the result of stent compression and intimal hyperplasia, illustrates the previously theoretic risk associated with placement of the balloon-expandable stent in a compressible site such as the cervical carotid artery. In addition, we demonstrate that significant intimal hyperplasia may occur after carotid artery stent placement, potentially limiting long-term patency.

Aged↗
PubMed1997

Welfare implications of gas stunning pigs: 3. The time to loss of somatosensory evoked potentials and spontaneous electrocorticogram of pigs during exposure to gases.

Changes in the spontaneous electrocorticogram (ECoG) and somatosensory evoked potentials (SEPs) were recorded in 12 pigs in each of three gas killing treatments. The treatments were 90% argon in air with 2% residual oxygen; a mixture of 30% carbon dioxide and 60% argon in air with 2% residual oxygen; or 80-90% carbon dioxide in air. The mean times to loss of SEPs were 15, 17 and 21 s, respectively. The mean time to loss of SEPs recorded during killing with a high concentration of carbon dioxide was significantly longer than those recorded for the other two gas killing treatments (P < 0.05). Slow waves (high amplitude and low frequency) appeared on average 15 s after exposure to argon. In some pigs killed with the carbon dioxide-argon mixture, a decrease in the frequency of electrical activity was apparent, although slow waves did not appear during killing with a higher concentration of carbon dioxide. A suppressed ECoG (reduction in amplitude of signals) was recorded at 22 and 20 s respectively, during exposure to the carbon dioxide-argon mixture and 80-90% carbon dioxide in air, but the onset of ECoG suppression could not be determined exactly during exposure to 90% argon in air. The time to onset of an isoelectric ECoG was 54, 39d and 32 s after exposure to argon, carbon dioxide-argon mixture and a high concentration of carbon dioxide, respectively. The mean time to the onset of an isoelectric ECoG during exposure to argon was significantly longer than that recorded for the other two gas killing treatments (P < 0.05). Based on the time to loss of SEPs, it is concluded that during killing with a high concentration of carbon dioxide, pigs would have to endure a moderate to severe respiratory distress induced with this gas for a considerable period of time prior to the loss of brain responsiveness. Argon-induced anoxia appears to be the first choice from a welfare point of view for killing pigs, based on its lack of aversive properties and its effectiveness in rapidly abolishing brain responsiveness. A mixture of 30% carbon dioxide and 60% argon in air is considered to be more humane than using a high concentration of carbon dioxide, as the time to loss of brain responsiveness is similar to that using 90% argon in air.

Animal Welfare↗