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Biomedical subjects

H Jackson

Publications and source records attributed to H Jackson.

At least 91 records · Page 5Linked to original sources

Lymphocyte subpopulations in pyogranulomas of caseous lymphadenitis.

Pyogranulomas of ovine caseous lymphadenitis (CLA) are encapsulated lesions resulting from infections with Corynebacterium pseudotuberculosis, a bacterial pathogen able to grow within macrophages. Immunohistology of CLA lesions showed a band of lymphocytes lining the inside of the collagen capsule in intimate contact with necrotic tissue, the intracapsular lymphocytes being organized into three layers. The innermost layer, immediately adjacent to the central necrotic tissue consisted of a narrow band of MHC class II staining macrophages. Cells staining for CD4, CD8 and gamma delta T cell markers were unevenly distributed throughout the lymphoid layer, tending to be more numerous immediately external to the macrophage layer. The intracapsular lymphoid tissue contained a high proportion of CD8+ lymphocytes (CD4:CD8, 1.5:1) and of gamma delta lymphocytes (CD4:CD8:gamma delta, 1:0.7:0.8). External to the T cell-rich zone and adjacent to the surrounding collagen capsule was a dense band of cells, a proportion of which stained atypically for CD45R and were tentatively identified as B cells. CD8+ and gamma delta+ T cells showed similar distributions and their relative abundance, compared with CD4+ T cells, was a distinguishing feature of the CLA lesion. Staining for factor VIII-related antigen clearly showed endothelial venules throughout the intracapsular lymphoid tissue. The presence of endothelial venules and the organized architecture of the lymphoid tissue teleologically argues that lymphocytes are continually recruited into chronic CLA lesions and play an important role in the ongoing disease process.

Animals↗

Should nylon corneal sutures be routinely removed?

Three groups of patients who had undergone cataract extraction through a corneal incision closed with 10/0 nylon sutures one, two, and three years previously were recalled to determine the incidence of suture related complications. Broken corneal sutures were found in 87.5% of patients after two years and 90% after three years and were causing symptoms in over half the patients. It is recommended that 10/0 nylon corneal sutures be routinely removed no later than one year after surgery.

Cataract Extraction↗

Anticonvulsant action of an arylamine-containing fraction from Agelenopsis spider venom.

A low molecular weight fraction (AG2) containing arylamine compounds has been isolated from venom of the spider Agelenopsis aperta. When administered intravenously or intracerebroventricularly, AG2 produces dose-dependent suppression of behavioral convulsions induced in rats by kainic acid, picrotoxin, or bicuculline. The low molecular weight compounds in spider venoms may provide novel tools for anticonvulsant research and therapy.

Animals↗

Testicular endocrine effects of alkane methanesulphonates related to the Leydig cell cytotoxic compound, EDS.

A series of compounds structurally similar to the specific Leydig-cell-cytotoxic substance ethane-1,2-dimethanesulphonate (EDS) were examined for Leydig cell toxicity in the rat. Within 48 h of a single injection of butane-2,3-dimethanesulphonate (BDS), propan-1,3-dimethanesulphonate (P-1,3-DS) or propan-1-chloro-2,3-DS (PCDS) there was a reduction in serum and testicular testosterone levels. The serum luteinizing hormone (LH) concentration was reduced following BDS or P-1,3-DS, and Leydig-cell LH receptors (measured by 125I-labelled hCG binding) were reduced by less than 15%, from which it is concluded that these compounds are not selectively toxic to Leydig cells. However, PCDS reduced human chorionic gonadotropin (hCG) binding by greater than 70% and could be considered to be a potential toxin. The effects of hydroxy-ethanemethane-sulphonate (HEMS), 1,5,2,4-dioxadithiepane-2,2,4,4-tetraoxide (cyclic SOSO), PCDS, propan-2,3-DS, alpha-chlorohydrin and cyclohexane-1,2-dimethane-sulphonate were compared with the effects of EDS 7 days after injection. Systemic toxicity, indicated by a loss of body weight, was associated with cyclic SOSO, PCDS and EDS, although only EDS and PCDS reduced both testicular hCG binding and serum and testis testosterone levels consistent with Leydig-cell toxicity. Further studies indicated that the potency of PCDS in reducing testicular hCG binding and serum and intratesticular testosterone levels was similar to that of EDS. However, unlike EDS, PCDS was systemically toxic and also reduced LH, which could at least in part account for changes in testosterone secretion. The experiments confirm the unique cytotoxicity of EDS. Loss of specific Leydig-cell cytotoxicity and an increase in systemic toxicity occurred when the EDS molecule was altered, even if the distance between the alkylating centres was maintained. The mechanism of action of EDS remains elusive.

Animals↗

The tissue distribution in rats of [195mPt]carboplatin following intravenous, intraperitoneal and oral administration.

[195mPt]carboplatin has been administered intravenously, intraperitoneally and orally to Wistar rats and the tissue distribution, metabolism, and pharmacokinetics of the drug investigated. The urinary and faecal excretion and toxicity following oral [195mPt]carboplatin administration has also been studied. Virtually identical results have been observed following i.v. and i.p. administration, indicating a rapid absorption of the unaltered compound from the abdominal cavity into the systemic circulation. Thus i.p. administered drug should produce a similar therapeutic response as i.v. administration, but may produce an additional local effect within the peritoneal cavity. Orally administered compound shows a pattern of distribution which is similar to that following parenteral injection for all tissues (except for the increased relative concentration in the stomach tissue), the concentration being lower by a factor of 4-5. However, the overall fraction of the dose retained within the body at 24 h is similar to that following i.v. administration. The toxicity is considerably lower for the orally administered drug compared with i.v. injection. These results clearly show that oral doses could be adjusted to produce a comparable therapeutic effect as i.v. or i.p. doses, and should also result in a higher efficacy against gastric carcinomas than achievable with parenteral administration.

Administration, Oral↗

Attitudes, knowledge, experience and behaviour related to HIV and AIDS among Zimbabwean social workers.

A recent study of Samuels & Boyle (1989) examined knowledge, attitudes, and behaviours of social service team members in Newham, East London in relation to HIV and AIDS. This study extends theirs to investigate social workers, both experienced and in training, in Harare, Zimbabwe, Whilst overall, there appear to be high levels of knowledge and positive attitudes displayed by these social workers, detailed examination of their responses shows gaps in knowledge and ambivalent attitudes and behaviours. These issues should be addressed when planning AIDS training courses.

Acquired Immunodeficiency Syndrome↗

Adaptations of synaptic form in an aberrant projection to the avian cochlear nucleus.

Surgical removal of the otocyst in chick embryos induces axons from the contralateral cochlear nucleus (nucleus magnocellularis, NM) to form, in addition to their normal endings in nucleus laminaris (NL), anomalous and persistent functional contacts in the ipsilateral NM (Jackson and Parks, 1988). We have examined how interaction between the abnormal synaptic partners during development influences the form of the axon terminal and its relation to the target neuron. In the light microscope, aberrant axon terminals labeled in vitro with HRP appear to form boutons quite unlike the large calycine endbulbs made by the normal cochlear nerve (CN) endings in NM. In the electron microscope, however, the anomalous endings appear embedded in the NM cells, something never seen normally in NM or NL. Morphometric analyses were performed on electron micrographs from NM and NL in animals aged embryonic day (E) 19 to posthatching day (P) 2 from which the right otocyst had been removed on E3 and in normal control animals. Aberrant endings appose 18% of the circumference of operated NM cells, versus 45% for CN axons in the normal NM at this age. The mean length of membrane apposition for the anomalous NM-to-NM endings was 215% greater than for normal NM-to-NL endings but 54% smaller than that in normal CN endings. These results support the idea that developmental interactions between synaptic partners can influence the form of the contact between the 2 neurons. The results also demonstrate, however, that formation of persistent and functional synapses with NM neurons throughout development is not sufficient to induce any axon to assume the calycine form of a cochlear nerve endbulb.(ABSTRACT TRUNCATED AT 250 WORDS)

Adaptation, Physiological↗

The level of differentiation of megakaryocyte progenitors and the subsequent modulation of megakaryocyte antigens on developing colony cells.

Human megakaryocyte development was studied in cell culture by first determining the differentiation stage of the clonable progenitor cell population and then analyzing the kinetics of expression of two megakaryocyte antigens using an immunoalkaline phosphatase system. Studies on the expression of two antigens present on megakaryocytes but not detectable on platelets (Mk-A, Mk-B) revealed that Mk-A antigen was found on megakaryocytes in colonies of less than six to eight cells at early times of cell culture. By contrast, Mk-B antigen was detected only in large megakaryocytes starting day 7 of culture and observed primarily in colonies of greater than eight cells. These studies show that human megakaryocyte progenitors are among the more mature of the precursor classes and link the antigen A bearing megakaryocytes to the developmental sequence as the immediate progeny of the precursor population with limited mitotic capacity. Amplification of antigen B expression is late in the developmental process, being detected by this method on only large megakaryocytes in well-formed colonies after 7-9 days of culture.

Agar↗

Quantification of urinary 3-hydroxyisovaleric acid using deuterated 3-hydroxyisovaleric acid as internal standard.

Deficiency of biotin at the tissue level can be assessed indirectly by measuring the urinary excretion of 3-hydroxyisovaleric acid. This paper describes the application of an improved method of quantifying urinary 3-hydroxyisovaleric acid using unlabeled and uniformly deuterated 3-hydroxyisovaleric acid. These compounds were synthesized by a modification of the lithioacetic acid method for generation of beta-hydroxy acids. Elemental analysis, nuclear magnetic resonance, gas chromatographic and gas chromatographic/mass spectrometric data demonstrated that the compounds are greater than 95% pure. Mass spectrometry confirmed the identity of the unlabeled compound, demonstrated that the deuterated compound is uniformly labeled, and offered insight into the pattern of mass fragmentation. The method for determination of the concentration of 3-hydroxyisovaleric acid in rat urine uses gas chromatographic/mass spectrometric quantification of the di-trimethylsilyl derivative with the deuterated compound as the internal standard. Results provide evidence that this method is more accurate than a previously published method that did not utilize the unlabeled and deuterated standards.

Animals↗

5-HT1A-receptor antagonism: N-alkyl derivatives of (R)-(-)-8,11-dimethoxynoraporphine.

Prompted by previous findings that a p-dimethoxy substitution pattern on an aromatic ring permits retention of dopaminergic agonist effects in certain ring systems, catechol derivatives of which are potent dopaminergic agonists, an 8,11-dimethoxy substitution pattern was introduced into the aporphine ring in place of the 10,11-dihydroxy moiety in apomorphine. Acid-catalyzed rearrangement of an appropriate morphine derivative provided the aporphine ring system with retention of the stereochemical integrity of the 6a asymmetric center. The hydroxyl group at position 10 was removed by catalytic hydrogenolysis of its phenyltetrazoyl ether. The methyl ether of the resulting 11-hydroxyaporphine was iodinated in high yield at position 8 with trifluoroacetyl hypiodite. This is the first account of synthesis of an iodinated aporphine derivative. The 8-iodo substituent was replaced with methoxyl by reaction with sodium methoxide and cuprous iodide. Neither the N-methyl target compound 7 nor the N-n-propyl derivative 8 demonstrated dopaminergic nor serotonergic agonism. However, 7 exhibited receptor-binding characteristics and other pharmacological properties suggesting that it may be a 5-HT1A receptor antagonist.

Animals↗