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Biomedical subjects

G Baxter

Publications and source records attributed to G Baxter.

At least 37 records · Page 2Linked to original sources

Successful thrombolysis of SVC thrombosis associated with Hickman lines and continuous infusion chemotherapy.

In a pilot study of continuous infusion 5-fluorouracil and intermittent bolus doxorubicin and cyclophosphamide in women with breast cancer, four of 24 patients developed symptomatic superior vena cava or innominate vein thrombosis associated with the Hickman line, despite prophylactic treatment with very low dose warfarin (1-3 mg/day). In all four patients, local thrombolysis with streptokinase was successful and chemotherapy was continued through the Hickman line under anticoagulant cover, maintaining an international normalized ratio of 2.0-3.0. No patient developed recurrent thrombosis. Prophylactic anticoagulation should be considered in patients receiving continuous infusion chemotherapy through Hickman lines, as they are at risk of proximal vein thrombosis. A randomized study is needed to address the question of the optimum anticoagulant regimen to prevent such thromboses.

Adult↗

Repopulation of blood lymphocyte sub-populations in rheumatoid arthritis patients treated with the depleting humanized monoclonal antibody, CAMPATH-1H.

Patients with severe rheumatoid arthritis who had failed treatment with conventional therapies were treated with a course of five or 10 daily intravenous infusions of CAMPATH-1H, a humanized antibody against the CD52 antigen, resulting in profound depletion of peripheral blood mononuclear cells. During the subsequent 18 months, lymphocytes were analysed for sub-populations by fluorescence-activated cell sorter (FACS) and for proliferation in response to polyclonal T-cell stimulation with anti-CD3 or staphylococcal enterotoxin B (SEB). Treatment resulted in almost complete depletion of lymphocytes from the blood followed by gradual repopulation. CD16+ natural killer (NK) cells and CD14+ monocytes returned to pretreatment levels within 1-2 months. CD19+ B cells returned to within 50% of pre-treatment levels by day 66 and to within normal range by day 150, whereas CD8+ T cells recovered to 50% of pretreatment levels by day 66, but did not show any further increase during the rest of the study period. The most profound effects were on the CD4+ T lymphocyte sub-population, as the mean CD4+ count did not increase above 20% of pre-treatment level at any time during the study period (550 days), at all the doses tested. The T cells which initially repopulated the blood 1-2 months after treatment, nearly all expressed the activation markers human leucocyte antigen (HLA)-DR and CD45RO, although the percentage of T cells expressing these molecules gradually declined to normal levels over time. Proliferative responses to polyclonal T-cell stimulation (anti-CD3 and SEB) were also significantly reduced in the first few months after treatment, but recovered to pre-treatment levels by day 250. The relationship between these observations and the clinical response is discussed.

Antibodies, Monoclonal↗

Emergence of CD52-, glycosylphosphatidylinositol-anchor-deficient lymphocytes in rheumatoid arthritis patients following Campath-1H treatment.

CD52 is a glycosylphosphatidyl-inositol (GPI)-linked glycoprotein expressed at high levels on normal T and B lymphocytes and at lower levels on monocytes, while being absent on granulocytes and bone marrow stem cell precursors. The emergence of CD52- lymphocytes of both T and B cell lineages was observed in three out of 25 rheumatoid arthritis patients treated with teh humanized antibody Campath-1H in phase II clinical trial. Whereas the majority of CD52- B cells had disappeared from the peripheral blood by 3 months post-treatment, both CD52- CD4+ and CD8+ T cells persisted in the circulation for at least 20 months. In the two patients that were tested, the GPI-anchored surface molecules CD55 and CD59 were also absent on the CD52- cells, although expression of other cell surface transmembrane, proteins (CD3, CD4 and CD2) was unaffected. The CD52- cells maintained a stable phenotype in vitro despite repeated re-stimulation in culture. Both CD52- and C52+ clones, established from one of the patients, responded to a similar extent to several T cell mitogens, as assessed by proliferation, suggesting that a general defect in expression of GPI-linked molecules does not impair T cell activation. These data show that an immune attack against a GPI-anchored surface molecule can result in the selection of a GPI-anchor-deficient cell population. Despite the persistence of CD52- T cells in the peripheral blood, no adverse reactions associated with the presence of these cells were noted in any of the patients; in fact they responded with longer remission times after Campath-1H treatment than the other patients in the trial.

Adult↗

5-HT2 receptor subtypes: a family re-united?

The current classification for 5-HT2 receptors accommodates three subtypes. In addition to the originally defined 5-HT2 receptor, sanctuary is now provided for the structurally related 5-HT1c receptor (now 5-HT2c) and at least one atypical 5-HT receptor subtype. The strong functional union of this family is reflected in the paucity of ligands that will discriminate between its subtypes and prompts some re-evaluation of the activities of compounds which may now be regarded as nonselective for the receptor subtypes in this class. In this article, Gordon Baxter and colleagues examine the pharmacology of both officially recognized and atypical 5-HT2 receptor subtypes. A number of novel selective agents are highlighted, some of which may prove useful for 5-HT2 receptor classification and, ultimately, clarify the mechanistic basis for current and future therapeutic strategies which target this receptor family.

Animals↗

Renal artery stenosis managed by Palmaz stent insertion: technical and clinical outcome.

OBJECTIVE: To assess the technical and clinical outcome of Palmaz renal artery stent insertion in patients with renal artery stenosis. DESIGN: Twenty-nine patients with radiological evidence of renal artery stenosis and hypertension (16 patients, mean +/- SD diastolic blood pressure 100.5 +/- 8.16 mmHg) and/or renal impairment (17 patients, mean +/- SD serum creatinine 376 +/- 169 mu mol/l) were referred for radiological intervention. Of these, 22 had ostial atheromatous lesions, six had atheromatous non-ostial lesions and one patient had fibromuscular dysplasia. Palmaz stent insertion was performed where either previous or concomitant percutaneous transluminal renal angioplasty (PTRA) had been unsuccessful. Technical success was defined primarily as <30% residual stenosis. A prospective radiological and clinical follow-up was performed and the results compared with the outcome following PTRA alone in a similar group of patients from our centre. RESULTS: Immediate technical success was achieved in all 29 patients. Follow-up angiography in 24 patients after a mean of 7 months showed restenosis in four patients. The hypertension was not 'cured' in any patient; a blood pressure fall was observed in seven patients (44%) and no change in the remaining nine subjects (56%). Renal function improved in four patients (24%), two of whom had angiotensin converting enzyme inhibitor-exacerbated renal impairment. This compares with an immediate technical success of 81% for PTRA alone, with cure in 50% and improvement in 32% of patients with hypertension and improvement in renal function in 64.7% of patients with renal impairment. CONCLUSIONS: Palmaz renal artery stent insertion has a higher technical success rate than PTRA, but the clinical improvement is disappointing in our patient population.

Adult↗

Quantitation of human immunodeficiency virus type 1 during pregnancy: relationship of viral titer to mother-to-child transmission and stability of viral load.

To develop strategies to prevent mother-to-child transmission of human immunodeficiency virus type 1 (HIV-1), it is important to define the factors determining it. We examined the relationship between maternal HIV-1 titer and the occurrence of mother-to-child transmission. In addition, we quantitated HIV-1 longitudinally in mothers during pregnancy, at delivery, and up to 1 year postpartum. To examine transmission, we prospectively studied 19 mother-child pairs; in 5 pairs, HIV-1 transmission occurred. We used endpoint dilution culture of peripheral blood mononuclear cells to determine maternal viral titer and found that although 4 of 6 (67%) women with viral titers of > or = 125 HIV-1 infectious units per 10(6) cells transmitted HIV-1 to their infants, only 1 of 13 (7.6%) women with lower viral titers transmitted (P = 0.01). Twelve of the 19 mothers had HIV-1 loads determined serially 3-8 times over periods ranging from 18 to 65 weeks. Viral titers varied greatly between the 12 women, but the viral load in each woman remained stable over time. In this cohort, HIV-1 viral load remained stable during pregnancy and the greater the maternal viral burden, the more likely that transmission occurred. These two related findings suggest that determination of HIV-1 titers early in pregnancy may predict which women are at high risk of transmitting to their infants and may be used to counsel HIV-1-infected women of childbearing age. These data identify maternal viral titer as a major determinant of mother-to-child HIV-1 transmission and thereby provide the scientific rationale for therapeutic strategies designed to interrupt transmission by lowering viral load.

Acquired Immunodeficiency Syndrome↗

Effects of tumor necrosis factor on in vitro digital arterial responses in horses.

Endotoxin given in vivo has been shown to inhibit endothelial dependent relaxation, and augment adrenergic (norepinephrine) contractions in isolated palmar digital arteries of horses. A study, using tumor necrosis factor (TNF) in vitro, was performed to determine the possible cause of these vascular alterations. Palmar digital arteries were surgically removed from 6 horses under general anesthesia, cut into 4-mm vascular rings (4 segments/horse), suspended in tissue baths, and attached to force displacement transducers for measurement of vascular tension. Four in vitro treatment groups were evaluated: group 1, control; group 2, TNF (5,100 pg of TNF/ml); group 3, 10 x TNF (10 times previous TNF concentration); group 4, TNF plus L-arginine (5,100 pg of TNF/ml and 10(-6) M L-arginine). The appropriate drug(s) was/were added to each tissue bath 10 minutes before dose-response tests were performed for acetylcholine, bradykinin, norepinephrine, and 5-hydroxytryptamine (serotonin). Concentrations needed to induce 50% maximal relaxation or contraction (EC50) and maximal percentage relaxation or contraction were determined. Arteries exposed to TNF (group 2) had significantly (P = 0.04) decreased maximal relaxation to acetylcholine and increased maximal contraction to norepinephrine, compared with control arteries, but values did not differ from those for arteries of groups 3 and 4. Maximal relaxation to bradykinin or contraction to serotonin were not different between treatment groups. Mean EC50 values for bradykinin, norepinephrine, and serotonin did not differ among the 4 treatment groups. Mean EC50 values for arterial segments' response to acetylcholine in group 4 were significantly (P = 0.04) increased, compared with control segments, but did not differ from those for segments of groups 2 and 3.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Constitutive presence of a catalytic fragment of protein kinase C epsilon in a small cell lung carcinoma cell line.

Protein kinase C (PKC) has been implicated in a variety of cellular responses such as proliferation, differentiation, and secretion. We assessed the role of PKC in the mitogenic effects of gastrin-releasing peptide (in a small cell lung cancer (SCLC) cell line. Using antisera that specifically recognize the PKC isoforms alpha, beta, gamma, delta, and epsilon, we determined that PKC epsilon is the major isoform in the SCLC cell line NCI-N417, followed by PKC alpha and delta. In addition to the 90-kDa PKC epsilon, our anti-PKC epsilon antiserum specifically detected a 40-kDa immunoreactive protein. Treatment of the cells with either 20 nM phorbol myristate acetate or 50 nM GRP enhanced significantly the level of the 40-kDa protein in a time-dependent (1-8 h), cycloheximide-sensitive fashion. Subcellular fractionation revealed that 90% of PKC epsilon was in particulate form, while the 40-kDa immunoreactive protein was cytosolic. To test the hypothesis that the 40-kDa soluble protein represented a catalytically independent PKC epsilon fragment, cytosolic extracts were assayed for kinase activity. 45-50% of the activity was apparent in the absence of the PKC activators phosphatidylserine and diacylglycerol. This effector-independent kinase activity was further purified by affinity chromatography using a synthetic peptide corresponding to the pseudosubstrate region of PKC epsilon (ERMRPRKRQGAVRRRV) coupled to Sepharose. The partially purified protein, recognized by the anti-PKC epsilon antiserum, exhibited histone kinase activity with kinetics similar to those of the tryptically generated catalytic fragment of brain PKC epsilon. This activity was inhibited by staurosporine (IC50 = 1 x 10(-8) M) and by the pseudosubstrate inhibitor peptide (IC50 = 7.7 x 10(-8) M). The SCLC kinase and the brain PKC epsilon catalytic fragment were similar as indicated by the relative sizes of the PKC epsilon immunoreactive peptides generated with protease V8 from Staphylococcus aureus (Mr approximately 37,000, 34,000, 28,000, 26,000, and 25,000). Taken together, we conclude that a variant SCLC cell line expresses a constitutively active catalytic fragment of PKC epsilon. Regulation by 12-O-tetradecanoyl-13-acetate or GRP via de novo protein synthesis suggests a novel mechanism of control of PKC diversity with implications for small cell lung cancer and possibly other malignancies.

Amino Acid Sequence↗

Colour Doppler ultrasound in the management of a case of cranial arteritis.

Colour Doppler ultrasound allows simultaneous B scan and Doppler imaging and can be employed to determine the velocity of blood flow in the vasculature of the eye and orbit. We describe a case of cranial arteritis (giant cell arteritis) in which serial velocimetry recordings were obtained. At one stage in the disease process no blood flow was detectable in the orbit despite previously reliable recordings. This coincided with a deterioration of the clinical state of the patient as signified by recurrent anterior ischaemic optic neuropathy despite controlled symptomatology and erythrocyte sedimentation rate by prednisolone therapy. Subsequent increase in the immunosuppressive therapy was accompanied by a return of blood flow in the orbit. Colour Doppler ultrasound may prove to be a useful examination technique in the diagnosis and management of cranial arteritis.

Aged↗

Mechanism controlling ovulation rate in ewes in relation to seasonal anoestrus.

Three experiments were carried out during seasonal anoestrus in Finnish Landrace and Scottish Blackface ewes, to establish whether the differences between the breeds in ovulation rate are functional during the non-breeding season and are therefore independent of the mechanism controlling ovulation. In Expt 1, follicles greater than or equal to 2 mm in diameter were dissected from the ovaries of both breeds and incubated individually for 2 h to assess their ability to secrete oestradiol and testosterone. In both breeds, follicles producing greater than or equal to 500 pg oestrogen/ml/h (oestrogen-active) were readily identifiable from a population producing less (oestrogen-inactive). The number of oestrogen-active follicles in each breed was similar to the number of ovulations near the end of the breeding season. Oestrogen-active follicles also had more luteinizing hormone (LH) receptors and larger diameters than oestrogen-inactive follicles. There were, however, no significant differences between the two follicle types in follicular fluid or in-vitro testosterone concentrations. In Expt 2, seasonally anoestrous Scottish Blackface ewes were unilaterally ovariectomized; the second ovary was removed 7 days later. Follicles from both ovaries were processed as described for Expt 1; oestrogen-active follicles were categorized according to their ability to produce greater than 500 pg/ml/h. There were twice as many oestrogen-active follicles in the second ovary as in the first ovary; the number of oestrogen-active follicles in the second ovary was also similar to the total number of oestrogen-active follicles in both ovaries of the Scottish Blackface ewes in Expt 1.(ABSTRACT TRUNCATED AT 250 WORDS)

Anestrus↗

Evidence for the action of bovine follicular fluid factor(s) other than inhibin in suppressing follicular development and delaying oestrus in heifers.

The aim of this study was to investigate the importance of inhibin in the delay in return to oestrus in heifers induced by steroid-stripped bovine follicular fluid (bFF). Oestrous activity was synchronized in 18 Hereford x Friesian heifers with two injections of prostaglandin (PG) 12 days apart. At the time of the second PG injection (time 0), the animals were assigned at random to one of three experimental groups and received i.v. injections of 20 ml saline (controls, n = 6), whole bFF (FF group, n = 6) or bFF in which the bioactive inhibin content had been reduced by > 95% by immunoaffinity chromatography (-INH group, n = 6; inhibin content approximately 0.8 ml whole bFF) every 8 h for 2 days. In a dose-response study, 2.5 ml whole bFF was insufficient to delay oestrus consistently following a similar synchronization regimen. Blood samples were taken every 8 h, initially before each injection and then subsequently for a further 9 days for hormone analysis. Animals were observed every 8 h throughout the experiment for signs of behavioural oestrus. The ovaries of all animals were examined using real-time ultrasonography about 30 h after the second PG injection. Treatment failed to suppress peripheral follicle-stimulating hormone (FSH) concentrations, although a significant increase was observed in both treatment groups after cessation of injections. Progesterone concentrations fell immediately after the second PG injection in all animals and remained below minimum detectable concentrations in all treated animals for the remainder of the experiment. In control animals, progesterone rose above minimum detectable concentrations by day 6 and continued to rise until the end of the experiment. Analysis of samples taken from treated animals several days after observed oestrus revealed that all had apparently ovulated. Mean daily luteinizing hormone (LH) concentrations did not differ between treatment groups before ovulation, but after ovulation, mean daily LH was significantly reduced in control animals as progesterone concentrations rose. Follicular development, as assessed by the mean antral diameter of the largest follicle on a pair of ovaries at ultrasound examination, was significantly suppressed in treated animals compared with controls (P < 0.01) and there was no significant difference (P = 0.397) between the two treatment groups. Control animals displayed oestrus 68 h (+/- 8 SEM) after the second PG injection, but oestrus was delayed in treated animals to 186h +/- 5 (FF group) and 191 h +/- 6 (-INH group).

Analysis of Variance↗

3 beta-hydroxysteroid dehydrogenase inhibitor reduces ovarian steroid production but increases ovulation rate in the ewe: interactions with gonadotrophins and inhibin.

Two experiments were carried out during the breeding season in ewes, first to investigate the effects of oral administration of a 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) inhibitor (epostane) on the number of corpora lutea, and secondly to investigate the mechanism through which epostane acts. In the first experiment Dorset Horn ewes were treated orally with 25, 50, 100 or 200 mg epostane twice daily between days 10 and 15 of the oestrous cycle. All doses of epostane resulted in an increase in the number of corpora lutea per ewe, although the response was curvilinear, with the 25 mg dose showing the largest response and the 200 mg group the smallest response. Although there was no difference between groups in the number of ewes showing oestrus, the higher doses of epostane had a detrimental effect on fertility. In the second experiment Welsh Mountain ewes were treated twice daily with 25 mg epostane from day 10 of the oestrous cycle and the ovaries were removed for analysis during either the luteal or the follicular phases. Treatment significantly increased the number of follicles greater than 6 mm in diameter, but significantly reduced in-vitro follicular oestradiol and testosterone production. Despite a marked increase in peripheral inhibin concentrations there was no effect on in-vitro inhibin production. Epostane treatment also caused a significant reduction in peripheral FSH concentrations and an increase in mean LH concentration. The latter was due to an increase in LH pulse frequency during the luteal phase and LH pulse amplitude during the follicular phase. These results confirm that treatment of ewes with epostane orally has a significant effect on follicular steroidogenesis and causes a significant increase in the number of corpora lutea per ewe. This effect on ovulation rate is not via an increase in peripheral FSH concentration, but may be caused by a reduction in follicular steroid activity either directly on the ovary or via an alteration in the pattern of LH secretion.

3-Hydroxysteroid Dehydrogenases↗

Apparent alpha-inhibin subunit immunoactivity in porcine and ovine luteal extracts is due to interference by cytosolic proteases in the assay.

Immunoreactive alpha-inhibin (ir-inhibin) was measured in luteal homogenates and subcellular fractions of ovine and porcine corpora lutea (CL) and in pig granulosa cells (GCs), using a sensitive radioimmunoassay specific for the 1-26 amino acid sequence of the N-terminus of the alpha chain of porcine inhibin (p1-26 alpha-inhibin). Inclusion of N-ethylmaleimide (N-EM) and/or EDTA in the immunoassay had no effect on the measurement of p1-26 alpha-inhibin peptide standards, on ir-inhibin levels in ovine follicular fluid and serum, or on ir-inhibin in subcellular fractions of pig GC. Fractionation of porcine GC homogenates on sucrose gradients demonstrated a major particular peak of ir-inhibin (buoyant density, 1.15-1.21 g/cm3) with variable activity in the cytosol. The particulate ir-inhibin peak was released into the cytosol by pretreatment of GC homogenates with the saponin, digitonin, prior to fractionation. Porcine GC extracts contained a protein (M(r) 45,000) which immunoblotted against p1-26 alpha-inhibin antibody. In the absence of inhibitors of proteolysis, apparent ir-inhibin activity was very high in extracts of sheep and pig CL. However, inclusion of N-EM or EDTA in the radioimmunoassay significantly reduced ir-inhibin levels in porcine and ovine CL extracts in a dose-dependent manner. Measurements of peptide tracer integrity indicated that porcine luteal cytosol degraded 125I-labelled p1-26 alpha-inhibin peptide. Subcellular fractionation studies demonstrated high levels of apparent ir-inhibin in luteal cytosol fractions, with only minor activity peaks associated with particulate fractions; however, this material was not releasable by digitonin. Immunoblotting of detergent extracts of porcine luteal particulate fractions failed to demonstrate alpha-inhibin material, and immunocytochemical localization studies of alpha-inhibin in porcine and ovine luteal sections were negative. Our results are consistent with the intracellular packaging/storage of a form of alpha-inhibin (M(r) similar to that of alpha-inhibin subunit precursor) in the porcine granulosa cell. However, luteinization of the porcine follicle was associated with a dramatic fall in ir-inhibin content, and the loss of immunostaining for alpha-inhibin peptides. We conclude that porcine and ovine CL contain little, if any, authentic inhibin. These studies emphasize the importance of excluding proteolytic artefacts when measuring biological peptides in luteal tissue extracts by radioimmunoassay.

Animals↗

Rubinstein-Taybi syndrome.

Rubinstein-Taybi Syndrome was first described in 1957 but only in 1963 as a distinguishable type of moderate mental retardation. The cause is still unknown although some type of genetic origin is possible. No consistent chromosomal abnormality has been demonstrated, the chromosomal analysis is normal, and cases are generally not considered hereditary. The recurrent risk for siblings is approximately 0.1% but may be as high as 50% for offspring of patients with the syndrome. The Rubinstein-Taybi syndrome is not at present detectable before birth and is evenly found in both males and females. The syndrome was thought to be rare but an increase in the number of reported cases each year suggests it is not as rare as estimated. It is thought to occur in about 1 in 300,000 births, and since it has become readily identifiable, more than 400 cases have been reported worldwide.

Abnormalities, Multiple↗

Transmembrane signaling by interferon alpha involves diacylglycerol production and activation of the epsilon isoform of protein kinase C in Daudi cells.

The early events that occur after treatment of the highly interferon alpha (IFN-alpha)-sensitive human lymphoblastoid Daudi cell line with human leukocyte IFN-alpha have been examined. IFN-alpha treatment of Daudi cells results in a rapid and transient increase in the cellular content of diacylglycerol, which occurs in the absence of inositol phospholipid turnover, or an increase in intracellular calcium concentration. Furthermore, IFN-alpha treatment results in a selective, time-dependent activation of the Ca(2+)-independent epsilon isoform of protein kinase C (PKC), while the alpha isoform is unaffected by IFN-alpha treatment. In contrast, IFN-alpha treatment of an IFN-resistant subclone of Daudi cells had no effect on the diacylglycerol content of cells and on the activation of PKC-epsilon. The selective PKC inhibitor staurosporine blocked the transcriptional activation of IFN-alpha-stimulated genes, the cytoplasmic accumulation of mRNAs for these genes, and the induction of antiviral activity by IFN-alpha against vesicular stomatitis virus in IFN-sensitive cells. These observations suggest that transmembrane signaling of IFN-alpha involves diacylglycerol production and activation of PKC-epsilon in Daudi cells.

Alkaloids↗

Distinct mechanisms of regulation of protein kinase C epsilon by hormones and phorbol diesters.

In this study, we examined the effects of T cell activators on the regulation of protein kinase C (PKC) isozymes present in thymocytes. Using affinity-purified anti-PKC antisera, we determined that the major PKC isoforms in murine thymocytes are PKC beta and PKC epsilon. The CD4+/CD8+ thymocyte subset expressed high levels of both PKC beta and PKC epsilon, whereas the CD4-/CD8- subset expressed much less of both. PKC beta was down-regulated following treatment of thymocytes with phorbol 12-myristate acetate (PMA) (2 x 10(-8) M) or ionomycin (0.4 microM). In contrast, PMA did not induce the down-regulation of PKC epsilon. Ionomycin alone, however, induced PKC epsilon down-regulation, similar to its effect on PKC beta. Similar observations were made on a promonocytic cell line, U937, which expresses PKC alpha, PKC beta (Strulovici, B., Daniel-Issakani, S., Oto, E., Nestor, J., Jr., Chan, H., and Tsou, A.-P. (1989) Biochemistry 28, 3569-3576), and PKC epsilon. To facilitate the study of PKC beta and PKC epsilon, we established a Chinese hamster ovary cell line which expresses murine PKC epsilon in addition to endogenous PKC alpha and PKC beta. Both PKC isoforms (beta and epsilon) were mostly in particulate form. PMA treatment left the majority of immunoreactive PKC epsilon intact. By contrast, thrombin treatment caused the disappearance of particulate and cytosolic PKC epsilon (60% by 10 min and 80% by 1 h). PMA and thrombin promoted the down-regulation of PKC beta with similar kinetics (100% down-regulation by 3 h). These results indicate that: 1) thymocytes express PKC epsilon; and 2) this isozyme exhibits a novel form of regulation distinct from the other PKC isozymes.

Amino Acid Sequence↗

Educational needs of school personnel regarding child abuse and/or neglect.

From a review of literature a questionnaire was developed to identify problems related to child abuse/neglect in a rural school district. School administrators, regular and special education teachers, and counselors completed the survey to help establish more effective training programs. Analysis indicated that (1) school personnel need further assistance in dealing with problems pertaining to the maltreatment of students. (2) Formal, coordinated, workshop training for child abuse/neglect is needed. (3) Colleges and universities should offer instruction on abuse/neglect for persons preparing to work in schools. (4) School personnel need to be aware of and abide by the laws regarding reporting cases of abuse/neglect. (5) Improved communication among school, community, courts, and social service agencies is required for dealing wtih abuse cases. (6) School personnel should become more aware of what happens after abuse/neglect has been reported. Information from such analysis even for one school district can increase insight into problems.

Child↗