Biomedical subjects
Publications and source records attributed to H Jackson.
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Groups of BDF1 mice, inoculated either IM or by the intratesticular (IT) route with comparable numbers of L1210 cells, died within the same time range from the disseminated disease. Cyclophosphamide (100 mg/kg IP) given on day 6 after inoculation, when the disease was advanced, increased the lifespan by about 100%, but all the mice died. The same dose on day 3 effectively cured all mice inoculated IM, whereas those injected with cells into the testicular lymphatic sinusoidal system died with only a short prolongation of lifespan. The study indicates that L1210 cells present in the testis are relatively protected from the action of cyclophosphamide, and the experimental results are consistent with clinical evidence for the occurrence of relapse in children with ALL due to malignant lymphoblasts persisting in the testicular environment.
The onset of responsiveness to eighth nerve stimulation was examined in n. magnocellularis and n. laminaris, (second- and third-order neurons) of the chick brainstem auditory system. Extracellular microelectrode mapping techniques were used to examine postsynaptic responses in in vitro brainstem preparations. Two specific questions were addressed. First, what is the earliest time at which postsynaptic action potentials can be evoked in n. magnocellularis and n. laminaris by eighth nerve stimulation? Second, does responsiveness to eighth nerve stimulation develop along a spatial gradient in n. magnocellularis and, if so, how does this gradient compare with other developmental events observed in the chick auditory system? Postsynaptic responses in n. magnocellularis were first recorded at 11 days of incubation. Nucleus laminaris responses to direct stimulation of n. magnocellularis were also first recorded at 11 days, although n. laminaris responses to eight nerve stimulation were not seen until 12 days of incubation. A gradient of response development within n. magnocellularis was indicated by mapping of responsive sites on days 11-13. At 11 days, responses to eighth nerve stimulation were restricted to the most anteromedial portion of n. magnocellularis. Between 11 and 13 days, cells in increasingly more posterolateral portions of n. magnocellularis became responsive. This anteromedial-to-posterolateral gradient in n. magnocellularis is correlated with the basal-to-apical gradient of morphogenesis observed in the basilar papilla and morphogenetic gradients previously observed in n. magnocellularis and n. laminaris.
Synaptic potentials were examined in the second- and third-order auditory neurons of nucleus magnocellularis and nucleus laminaris in the chick. Brain stems of mature chick embryos were explanted and maintained in vitro for 4 to 8 h. Field potentials, extracellular spike potentials and intracellular potentials evoked by 8th-nerve stimulation were examined. Eighth-nerve stimulation reliability elicited four identifiable field potentials which could be attributed to: (i) the afferent volley of the 8th-nerve axons, (ii) postsynaptic responses of n. magnocellularis neurons, and (iii) ipsilaterally and, (iv) contralaterally-evoked n. laminaris postsynaptic responses. Intracellular-recorded postsynaptic potentials were characterized by a rapid rise time and short duration. They were apparently monosynaptic with a synaptic delay of 0.4 ms. In each n. magnocellularis neuron the 'fast' excitatory postsynaptic potentials were composed of 1 to 3 all-or-none components. 'Slow' excitatory postsynaptic potentials were characterized by a longer latency, a longer duration and graded amplitude variation in proportion to the intensity of 8th-nerve stimulation. Both 'fast' and 'slow' excitatory postsynaptic potentials had similar reversal potentials. Since the 8th nerve makes monosynaptic connection with n. magnocellularis neurons, it is likely that at this synapse the 'fast' excitatory postsynaptic potentials were produced, while the 'slow' potential may be attributable to the convergence of many boutonal synapses of unknown origin. Intracellular injections of horseradish peroxidase into n. magnocellularis revealed that its efferents bifurcate below the nucleus and send one axon to the contralateral n. laminaris while the other axon forms a highly divergent projection to the ipsilateral laminar nucleus. The intracellular records obtained from n. laminaris are consistent with this anatomical finding in that graded excitatory postsynaptic potentials were elicited by 8th-nerve stimulation.
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The anteroposterior radiographs of 50 patients with multiple fractures of the pelvic ring were analyzed and the findings compared with the interpretation made at the time of admission. Thirty-six of the 50 patients (72%) had associated sacral fractures. Sixty-one percent of the sacral fractures had been missed on the initial examination. Disruption, displacement, deformity, and density changes of the sacral arcuate lines are described as signs of sacral fracture.
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We studied the chick auditory system to determine whether there is a normal developmental reduction in the number of cochlear nerve axons innervating individual cochlear nucleus (nucleus magnocellularis, NM) neurons. We also examined the preterminal branching patterns of cochlear nerve axons during development. The number of cochlear nerve axons innervating individual NM neurons was estimated by counting the increments in the postsynaptic response as the intensity of cochlear nerve electrical stimulation was varied gradually; this number fell from a mean of 4.0 on embryonic day 13 (E13) to a mean of 2.2 on E17 and E18 and the 4th day after hatching. This highly reliable decline in functional convergence was accompanied by a decrease in the number of preterminal branches of cochlear nerve fibers innervating the NM. On E13 and E14, most axons stained by iontophoretic injections of horseradish peroxidase showed two distinct preterminal branches in the NM. By E17 and E18 and thereafter, cochlear nerve axons were unbranched and terminated with a characteristic single large calycine ending in the NM. There are about twice as many cochlear nerve axons as neurons in the NM and the number of fibers in the nerve appears to decline only slightly between E13 and E17. The 50% decline in the number of cochlear nerve axons making functional synapses on individual NM neurons therefore is associated principally with the concurrent elimination of cochlear nerve axon branching in the NM.
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Auxiliary bone marrow cells are required for optimal murine megakaryocyte colony formation in addition to progenitor cells and a colony stimulating activity (CSA) present in WEHI-3 cell conditioned medium. These auxiliary cells are adherent, with a sedimentation rate of 5.8 mm hr-1 and buoyant density of 1.065-1.078 gcm-3. The activity from bone marrow cells is loss at irradiation doses above 900 rad. Bone marrow cells with these characteristics, and supernatants from lung, bone shafts, and peritoneal exudate cells were all active in enhancing megakaryocyte colony incidences in mouse bone marrow cultures above those stimulated by an obligatory activity in WEHI-3 cell conditioned medium. Certain macrophage cell lines (J774, P388D1) could elaborate the activity. This study confirms that a potentiation activity enhances CSA stimulation of megakaryocyte colony formation. The potentiator is elaborated by bone marrow cells in limiting amounts requiring either high cell concentrations or an exogenous source of the activity for optimal colony growth.
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Addition of prostaglandin E2 (PGE2) significantly altered the cellular composition of murine long-term bone marrow cultures. After 4--5 weeks of culture, increased cellularity in the suspension phase was observed in all cultures containing prostaglandin. These suspension cells contained markedly higher proportions of differentiated neutrophils than did cells cultured in the absence of PGE2. Granulocyte-macrophage progenitor cell levels in the suspension layer were increased 3--20 fold after five weeks in prostaglandin-containing cultures compared with control cultures. Fewer cells comprised the adherent layer in cultures containing prostaglandin. The number of macrophages in this layer was reduced 3--8 fold in these cultures compared with control cultures, while the number of granulocytes was increased 2--3 fold. The progenitor cells biased toward macrophage development were selectively inhibited in the cultures with PGE2. There was no significant effect of PGE2 on pluripotent stem cell levels or on the longevity of the cultures. It is concluded that excessive monopoiesis in bone marrow may be limited by PGE2 without influencing either stem cell maintenance or the development of other marrow-derived cell types.
Due to the drawbacks in the potential use of alpha-chlorohydrin itself as a male oral contraceptive, two novel crystalline derivatives, alpha-chlorohydrin-bis-m-nitrobenzoate and alpha-chlorohyrdin-mono-p-acetamidobenzoate, were synthesized and tested for antifertility activity in male rats. In addition, the nephrotoxic effects of alpha-chlorohydrin itself and of the two aromatic esters were investigated by the use of diuretic experiments, plasma biochemical analyses and kidney histology. Both esters were found to be of comparable molar potency to alpha-chlorohydrin in inducing temporary infertility following daily oral administration. The nephrotoxic effects following high oral doses of alpha-chlorohydrin were largely eliminated by the use of either ester. These derivatives have several advantages over alpha-chlorohydrin, being crystalline compounds of definable purity. Although potency was retained, acute oral toxicity was greatly reduced, due to a combination of factors - the esters were poorly absorbed in high dosage whilst relatively slow breakdown permitted effective levels to be attained on epididymal spermatozoa.
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Pleomorphism of Cellulomonas acidula in liquid and on solid media is described. Growth in liquid medium is characterized initially by the formation of club-shaped rods and later by cocci. On solid media the organism formed irregular branched cells and large swollen cells.