Biomedical subjects
K Campbell
Publications and source records attributed to K Campbell.
Differential regulation of neuropeptide mRNA expression in intrastriatal striatal transplants by host dopaminergic afferents.
The effects of dopamine-specific manipulations on neuropeptide gene expression in intrastriatal grafts of fetal striatal tissue were studied by quantitative in situ hybridization histochemistry, using 35S-labeled oligonucleotide probes. Messenger RNA transcripts for the striatal neuropeptides preproenkephalin (PPE) and preprotachykinin (PPT) were detected in neurons forming discrete patches in the striatal grafts. The relative abundance of PPE and PPT mRNA-expressing neurons within the graft patches (51-54%) was similar to that found in normal caudate-putamen. In specimens with intact dopamine afferents the expression of PPE mRNA in grafted neurons was similar to that found in normal caudate putamen, whereas the hybridization signal for PPT mRNA was 27% higher in the graft neurons than in the normal caudate-putamen. Removal of host dopaminergic afferents by 6-hydroxydopamine lesions of the ipsilateral mesostriatal dopamine pathway increased the hybridization signal for PPE mRNA both in the grafts (+84%) and in the spared ipsilateral host caudate-putamen (+125%), whereas the PPT signal was reduced by 53% in the grafts and by 51% in the remaining host caudate-putamen. Similarly, chronic treatment of grafted animals with the dopamine receptor antagonist haloperidol (2 mg/kg per day for 10 days) produced a 146% increase in the PPE signal in the grafts and a 175% increase in the intact contralateral caudate-putamen, whereas the signal for PPT mRNA was again decreased by 52% and 51% in the grafts and host caudate-putamen, respectively. These results show that the host nigrostriatal dopamine pathway differentially regulates enkephalin and substance P gene expression within striatal grafts and thereby exerts a tonic functional influence over grafted striatal neurons.
Collateral sensitivity to nitrosoureas in multidrug-resistant cells selected with verapamil.
We have examined the effects of the nitrosoureas, streptozotocin (STZ) and 1,3-bis(chloroethyl)-1-nitrosourea (BCNU), on a human multiple myeloma cell line, RPMI 8226, and its drug-resistant variants. Cell lines selected for doxorubicin (DOX) resistance alone displayed a STZ and BCNU cytotoxicity profile similar to that of the parent cell line. In contrast, two of the drug-resistant variants selected with DOX plus verapamil, an agent which inhibits P-glycoprotein-mediated multidrug resistance, displayed a collateral sensitivity to STZ and BCNU. Verapamil was included in the selection protocol because it has been shown to inhibit the P-glycoprotein-mediated multidrug resistance phenotype and is now in clinical trials as a chemosensitizing agent. The collateral sensitivity to these nitrosoureas seen in the DOX plus verapamil-selected cell lines is due to the functional loss of a DNA repair molecule, O6-Methylguanine DNA methyltransferase (MGMT). The functional loss of MGMT is secondary to the loss of MGMT gene expression. The loss of MGMT gene expression is not due to loss or gross rearrangement of the MGMT-coding region. If this selection pressure applied in vitro reflects the in vivo situation, then new chemotherapeutic strategies may be devised to exploit this phenomenon. These cell lines will serve as useful models for delineating mechanisms which govern MGMT expression.
Nonoperative management of unilateral neonatal hydronephrosis.
We followed nonoperatively 45 neonates with unilateral hydronephrosis and suspected ureteropelvic junction obstruction for 30 months, regardless of the degree of hydronephrosis, shape of diuretic renogram washout curve or initial degree of functional impairment. Of the patients 30 had mild hydronephrosis and no renal deterioration, while 15 had severe hydronephrosis, an obstructed diuretic renogram and markedly decreased hydronephrotic kidney function. During followup percentage and absolute renal function rapidly increased in all patients, hydronephrosis improved in 7 and contralateral compensatory hypertrophy did not develop in any. These findings help to define the natural history of untreated hydronephrosis, suggest that many newborn kidneys with severe hydronephrosis are not obstructed despite even profound initial decreases in renal function and demonstrate that traditional tests for diagnosing obstruction are inaccurate in this age group. Therefore, the methods for assessing obstruction and the indications for surgical intervention in these patients require reexamination.
The evoked K-complex: all-or-none phenomenon?
The functional significance and topographical variation of the different components of the evoked K-complex were examined. In the first experiment, the intensity of the stimulus (80 and 60 dB SPL) and its rise-and-fall time (2 and 20 milliseconds) were manipulated during nonrapid eye movement sleep. In the second experiment the tonal frequency (500, 1,000 and 2,000 Hz) of the stimulus was manipulated. In the first experiment, nine stimuli were presented every 10 seconds, whereas in the second, 20 consecutive stimuli were presented. The evoked K-complex consisted of two different negative components peaking at approximately 350 and 550 milliseconds, respectively, and followed by a positive component peaking at approximately 900 milliseconds. K-complexes were easier to elicit for high-intensity fast rise-and-fall time stimuli than for low-intensity slow rise-and-fall time stimuli. The probability of occurrence was not affected by the tonal frequency of the stimulus. When a K-complex was evoked, the amplitude and latency of N350, N550 and P900 remained invariant regardless of its intensity, rise-and-fall or its tonal frequency. The N550-P900 portion of the K-complex therefore appears to be an all-or-none phenomenon. On trials in which a K-complex could not be elicited, N350 was still visible although much attenuated. In these trials, its amplitude was further reduced when stimulus intensity was lowered. N350 might need to reach a certain critical threshold before the much larger N550-P900 complex is elicited.
An injection of meperidine and an anti-nausea agent such as promethazine or prochlorperazine.
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The use of laboratory tests in a psychiatric hospital.
Little attention has been paid to the use of laboratory tests in psychiatric hospitals. This paper reviews studies of the use and abuse of laboratory tests in general medicine. It examines five different sets of test results performed over a three month period at a mid-sized psychiatric hospital. The paper concludes that, on the whole, the laboratory was used efficiently and effectively. However, some testing patterns need to be re-evaluated.
Nursing and midwifery: an opinion.
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Molecular cloning of putative odorant-binding and odorant-metabolizing proteins.
Olfactory reception occurs via the interaction of odorants with the chemosensory cilia of the olfactory receptor cells located in the nasal epithelium. The cDNA clones from mRNA specific to olfactory mucosa were studied. One of these clones, OBPII, encodes a secretory protein with significant homology to odorant-binding protein (OBP), a protein with broad odorant-binding ability, and is expressed in the lateral nasal gland, which is the site of expression of OBP. The OBPII sequence also shows significant homology to the VEG protein, which is thought to be involved in taste transduction. OBPII is a new member of the lipophilic molecule carrier protein family. The second cDNA clone encodes a novel homologue of glutathione peroxidase, an enzyme involved in cellular biotransformation pathways. Its expression appears to be localized to the Bowman's glands, the site of several previously identified olfactory-specific biotransformation enzymes.
Sequence of a truncated LINE-like retroposon dispersed in the genome of Culex mosquitoes.
The Juan elements belong to a family of reiterated sequences scattered through the genome of Culex mosquitoes. The nucleotide sequence of three Juan copies has been determined. The results show that the Juan elements are truncated retroposon-like elements belonging to LINEs.
Non-steroidal anti-inflammatory drugs and complicated diverticular disease: a case-control study.
Fifty patients with severe complications of diverticular disease were compared with two groups of 50 controls, matched for age and sex. The first control group (A) was randomly selected from all emergency hospital admissions, and the second group (B) from patients with uncomplicated diverticular disease. Of the 50 study patients, 24 (48 per cent) were taking non-steroidal anti-inflammatory drugs (NSAIDs) at the time of admission compared with nine (18 per cent) of control group A and ten (20 per cent) of control group B. Both of these differences were statistically significant, indicating a strong association between the ingestion of NSAIDs and the development of severe complications of diverticular disease.
The mouse IgH 3'-enhancer.
A lymphoid-specific transcription enhancer element has recently been identified at the far 3' end of the rat immunoglobulin heavy chain (IgH) locus. Sequence analysis presented here reveals that this enhancer is flanked by a 350-bp invert repeat, giving a structure reminiscent of a transposable element. We therefore screened for the equivalent enhancer in the mouse to determine whether its presence was conserved during evolution. A mouse homologue was indeed identified and is located 16 kb downstream of the C alpha 1 exon. It is also flanked by invert repeats and these are not repeated throughout the genome. The mouse and rat enhancers retain high sequence homology. As regard activity, the IgH 3'-enhancer is lymphoid specific. However, this activity was detected in two plasmacytoma lines tested but not in two B cell lymphomas nor in HeLa cells suggesting that the enhancer may only play a stage-specific role during lymphocyte differentiation. As regards function within the IgH locus, we found that inclusion of the mouse IgH 3'-enhancer (in addition to the intron-enhancer) on mu gene expression plasmids effected a small increase in mu mRNA levels in stable plasmacytoma transfectants.
Ovarian neoplasms and the risk of adnexal torsion.
Previous reports examining adnexal torsion suggested that benign ovarian neoplasms are more likely to undergo torsion than malignant ovarian neoplasms. To our knowledge, this clinical observation has not been quantified. To examine this hypothesis, we reviewed our experience with ovarian neoplasms found at the time of surgery over a 10-year period. Benign ovarian neoplasms had a 12.9-fold increased risk of undergoing adnexal torsion when compared with malignant ovarian neoplasms (95% confidence interval, 10.2 to 15.9). The histologic type of ovarian neoplasm does not appear to affect the rate of adnexal torsion. Adnexal torsion rarely involves cancer.
Congenital heart disease, parental stress, and infant-mother relationships.
The effect of congenital heart disease on early social relationships was assessed by observing 42 infants with the disease and 46 healthy infants in a standardized laboratory setting with their mothers. Significantly fewer infants with congenital heart disease, in comparison with healthy peers, were considered to have secure relationships with their mothers. The quality of the infant-mother relationship in the group with congenital heart disease was not related to parents' reports of their own stress or psychologic well-being. Severity of illness did not have a direct effect on the quality of the infant-mother relationship, but securely attached infants showed more subsequent improvement in health than insecurely attached peers showed. Attention to the infant-mother relationship in clinical care may improve the social development of babies with congenital heart disease and may have positive effects on physical health as well.
Long-term smoking intervention at the worksite: effects of quit-smoking groups and an "enriched milieu" on smoking cessation in adult white-collar employees.
Maximizing the potential of worksites for smoking intervention remains elusive. We hypothesized that long-term effectiveness of group intervention would be enhanced when offered within an "enriched milieu" (full program) compared with relative isolation (group only). The data failed to support the hypothesis. Although sustained abstinence rates were higher at full-program sites (50%) than at group-only sites (44%), the difference did not achieve statistical significance. Initial (35% vs. 47%) and 12-month (18% vs. 22%) quit rates at full-program and group-only sites also failed to demonstrate the "benefit" of the "enriched milieu."
A study of chromosome 11p13 translocations involving TCR beta and TCR delta in human T cell leukaemia.
A frequent site of translocation damage in human T-ALL has been localized to a specific region of chromosome band 11p13. Five new T-ALL cases are described which break in the major T-ALLbcr region of 11p13, two involving a novel translocation t(7;11)(q35;p13), with breakage at the T cell receptor (TCR) beta gene from 7q35, and three involving TCR delta from 14q11 in the more common t(11;14)(p13;q11). Analysis of the mechanism of one T-ALLbcr/TCR beta translocation and a previously described t(11;14)(p13;q11) was conducted by genomic cloning of translocation breakpoints, using the polymerase chain reaction (PCR). Both seem to have occurred by recombinase error, but only the t(7;11) showed sequence-specific joining. Nonetheless recombinase mediation of the t(11;14) is implied by the presence of N-region addition (a hallmark of recombinase joins) on both derivative chromosomes. These observations reinforce the view that translocations in the T-ALLbcr region of chromosome 11p13 are a major lesion in human T-ALL. In addition, these can occur by mimicry of VDJ joining, but sequence specificity is not obligatory.
Ca-ATPase isozyme expression in sarcoplasmic reticulum is altered by chronic stimulation of skeletal muscle.
Chronic stimulation of a predominantly fast skeletal muscle enhanced the expression of type I (slow muscle) Ca-ATPase and suppressed the expression of the type II (fast muscle) Ca-ATPase. Monoclonal antibodies IID8 and IIH11 against type I (slow) and type II (fast) isozymes respectively, were used to type the Ca-ATPases of the isolated SR (sarcoplasmic reticulum) by Western blots, and the Ca-ATPases of the muscle fibers by immunohistochemistry. Of the fibers from control muscles 80% stained for the type II isozyme and 20% for the type I isozyme. Following chronic stimulation all fibers stained for type I isozyme and none stained for type II isozyme. Ca-ATPase isozyme distribution in isolated SR confirmed this effect of chronic stimulation. The calcium uptake activities of homogenates of stimulated muscles were 22% of the control muscles. The Ca-ATPase and calcium-uptake activities of the isolated SR from stimulated muscles were, respectively, 32 and 45% of the control muscles.
Bilateral ovarian neoplasms and the risk of malignancy.
Bilateral ovarian neoplasms are believed more likely to be malignant than are unilateral neoplasms. To our knowledge, this clinical tenet has not been evaluated or quantified. To test this hypothesis, we conducted a 10-year review of ovarian neoplasms found at the time of celiotomy at the Women's Hospital, Los Angeles County-University of Southern California Medical Center. Overall, women with bilateral neoplasms had a 2.6-fold increased risk of malignancy when compared with women who had unilateral neoplasms (95% confidence interval, 2.0 to 3.4; p less than 0.001). The age-standardized relative risk was 1.8 (95% confidence interval 1.4 to 2.3). When standardized for the effect of menopausal status, the relative risk was 2.0 (95% confidence interval, 1.6 to 2.5). Bilaterality is associated with a doubling in the risk of cancer, a highly significant difference.