Biomedical subjects
Publications and source records attributed to R L Cooper.
We report a transient, erythematous dermatitis that formed in 2 infants shortly after breast-feeding from their mothers who had ingested food flavored with red pepper, although the mothers did not display any signs of dermatitis.
The presence of noradrenergic neuronal innervation in the ovaries and cyclic alterations in ovarian noradrenaline suggest a role for such innervation in oocyte release. The current experiments evaluated the relationship between ovulation and alterations in ovarian concentrations of noradrenaline induced by unilateral, intrabursal administration of the specific noradrenergic neurotoxin DSP4. Intrabursal injections of DSP4 (0-10 mumoles per ovary) given at 19:00 h at pro-oestrus induced a prompt, dose-related reduction in ovarian noradrenaline on the injected and non-injected sides. Although this result suggests that injected material was reaching the contralateral ovary, ovulation was suppressed only on the injected side. This suppression was persistent, and lasted through at least the next two cycles following either unilateral or bilateral treatment. The reductions in noradrenaline could be mostly, if not entirely, attenuated by prior administration of desipramine which blocks re-uptake of noradrenaline, while the ipsilateral ovulatory effects remained unchanged. Although it has been reported that DSP4 binds the opiate receptor, intrabursal co-administration of the antagonist naloxone was ineffective in altering ovulatory suppression. These results suggest that while decreases in ovarian noradrenaline in response to local exposure to a noradrenergic neurotoxin may accompany a reduction in oocyte release or a block in ovulation, the anti-ovulatory effect of DSP4 is independent of the changes in noradrenaline concentrations and may be due to some other ovarian response.
The Glaucoma Inheritance Study in Tasmania (GIST) is a population survey of Australia's island state, Tasmania (population 450,000). Its aim is to find families with autosomal dominant, adult-onset, primary open angle glaucoma (POAG) suitable for genetic linkage analysis. POAG is relatively common, affecting around 3% of the Australian population. By finding the large families with POAG and identifying all the descendants in a captive population, it is possible that there may be overlap of different glaucoma pedigrees. Three of the first thirteen families in the study were composed of overlapping pedigrees. In one GIST family, GTas3, there has been intermarriage with other pedigrees with glaucoma on five occasions. The possibility of multiple genotypes was also reinforced by the inability to determine a single glaucoma phenotype in this family. When finding large families of POAG for linkage analysis, researchers must be aware of the risk of affected individuals inheriting their gene from the alternate parent. Thus, the alternate parents or their families must be examined, especially if the phenotype is atypical for the rest of the family.
Synaptotagmin-like immunoreactivity was shown to be localized at crayfish neuromuscular junctions by whole mount immunocytochemistry. Synaptotagmin-like immunoreactivity was present in both phasic and tonic excitatory terminals and inhibitory nerve terminals. Immunoblots indicated that the antibody DSYT-2 raised against Drosophila synaptotagmin, labelled proteins at relative molecular weights of 87 kDa and 107 kDa in crayfish ganglion and neuromuscular preparations.
PURPOSE: To measure the tissue pressure gradient through the optic disk and to determine the relationship between intraocular, cerebrospinal fluid, and retrolaminar tissue pressures. The relationship of optic nerve subarachnoid space pressure to intracranial cerebrospinal fluid pressure also was explored. METHODS: Micropipettes coupled to a pressure transducer were passed through pars plana and vitreous to enter the optic disk in the anesthetized dog. Using a micromanipulator, pipettes penetrated the optic disk in steps while pressure measurements were taken. In some animals, pipettes also were passed into the optic nerve subarachnoid space. Lateral ventricle cerebrospinal fluid pressure, intraocular pressure, and arterial blood pressure were measured concurrently, and the effect of raising CSF pressure was explored. RESULTS: Retrolaminar tissue pressure was largely dependent on the surrounding cerebrospinal fluid pressure, which was on average 8.6 +/- 3.5 mm Hg (SD, n = 8) higher, and was independent of intraocular pressure. Most (85% +/- 15% [SD, n = 8]) of the pressure drop between intraocular pressure and retrolaminar pressure occurred across the anterior 400 microns of disk tissue. When the intraocular pressure was 21 mm Hg and the cerebrospinal fluid pressure was zero, retrolaminar tissue pressure averaged 7 mm Hg and the translaminar pressure gradient was 3.08 +/- 0.29 mm Hg/100 microns tissue (SD, n = 3). Optic nerve subarachnoid space pressure was equivalent to lateral ventricular pressure. CONCLUSIONS: These results show that cerebrospinal fluid pressure largely determines retrolaminar tissue pressure; hence, along with intraocular pressure, it is of major importance in setting the translaminar tissue pressure gradient. Results also demonstrate hydrostatic continuity between the optic nerve subarachnoid space and the lateral ventricle. That the translaminar pressure gradient can vary independently of intraocular pressure may be of importance in understanding the pathophysiology of glaucoma.
The opener muscle in the walking legs of the crayfish (Procambarus clarkii) is innervated by only one excitatory motor neuron, yet excitatory postsynaptic potentials (EPSPs) of proximal fibers are eightfold larger than those of central muscle fibers at low frequencies of activation, due in large measure to differences in presynaptic properties. We investigated quantal release properties, calcium signals, and ultrastructure of presynaptic terminals to elucidate factors that could account for the physiological differences. Focal macropatch electrodes were placed over individual visualized terminal varicosities to obtain records of quantal contributions to the excitatory junctional current (EJC). At low frequencies of activation, mean quantal content is greater for proximal than for central varicosities. This difference is due to a higher probability of release per synapse, and not to a larger number of active synapses. Recorded varicosities were labeled with fluorescent beads deposited by the electrode. These beads adhered to the muscle fibers, outlining the recorded site for subsequent serial thin sectioning and reconstruction from electron micrographs. Comparisons of structure and function were made for individual varicosities. The number of active zones per terminal surface area and the number of synapses with multiple active zones (complex synapses) were greater in high-output varicosities. Calcium indicators were loaded into proximal and central nerve terminals by axonal injection to compare the relative differences in calcium buildup during stimulation. Presynaptic calcium signals were larger for proximal varicosities than for central varicosities.(ABSTRACT TRUNCATED AT 250 WORDS)
Lindane, gamma-1,2,3,4,5,6-hexachlorocyclohexane (gamma-HCH), has been shown to disrupt reproductive function in mammals. Many of these adverse effects on female reproduction such as alterations in sexual receptivity, disrupted ovarian cyclicity, reduction in uterine weight and termination of pregnancy are thought to be due to altered ovarian hormone secretions and/or an impaired response to circulating estrogen. It has been suggested that gamma-HCH may block the response of estrogen-dependent tissues to estradiol via an interaction with the estrogen receptor. To test this hypothesis, estrogen (ER) and progesterone (PR) receptor affinity and number were evaluated in sexually immature, 17 beta-estradiol-3-benzoate (EB)-primed Long Evans female rats following exposure to vehicle or gamma-HCH (40 mg/kg) for 7 days (Study 1) and in adult, ovariectomized EB-primed Long-Evans rats following gavage with vehicle or gamma-HCH (0, 10, 20, or 40 mg/kg) for 5 days (Study 2). Chlordecone (kepone; 40 mg/kg; i.p.) was used in Study 2 as a positive control for the alteration of the estrogen-induction of PR in the pituitary. Neither gamma-HCH nor chlordecone altered serum estradiol concentrations. gamma-HCH did not change the ER number (1, 24, or 30 h after EB) or the estrogen-dependent induction of PR (24 or 48 h after EB) in the hypothalamus (HYP), pituitary, or uterus. These data indicate that the effects of gamma-HCH on the female reproductive system do not involve an alteration in the ER and that heterogeneity exists between target tissues in their response to xenobiotics.
Decapoda Crustacea molt in order to grow; some species, such as the Dungeness crab Cancer magister, achieve a very large size. Does sensory neuron hyperplasia in internal proprioceptors accompany this growth? To determine this, neurons in propodite-dactylopodite (PD) chordotonal organs were counted in first walking legs of juvenile (5th through 9th instar) and adult (10th through 13th instar) C. magister. We found that the PD organs of J5 crabs have about 56 neurons; the number increases to about 61 neurons in J6 crabs. Significant hyperplasia now occurs because an average of 79 neurons are found in the PD organs of J7 crabs. Little to no hyperplasia accompanies the several succeeding juvenile and adult molts (ca. 82-86 neurons are present). Because autotomized limbs are regenerated upon molting, we also examined how the number of PD organ neurons in regenerated legs compares with those of pristine legs. Newly regenerated legs (termed 1st stage regenerates) have fewer sensory neurons than do their contralateral pristine partners (65 vs 81); larger regenerated legs which have attained nearly normal size as a result of additional molts (2nd stage regenerates) still have fewer neurons than their pristine partners (69 vs 81). Additionally, in contrast to those of pristine walking legs, the elastic strand of PD organs from 1st stage regenerates in a misshapen sheet containing a cluster of small neurons with no obvious functional organization. Nonetheless, neurophysiological recordings indicate that all the receptor types typical for pristine legs (movement and position cells) are represented. The PD organs of 2nd stage regenerates differentiate to the shape and neuronal organization of pristine legs.
Chlordimeform [N'-(4-chloro-o-tolyl)-N,N-dimethylformamidine] has been shown to cause a 1-day delay in the surge of luteinizing hormone (LH) in ovariectomized, steroid-primed female rats, presumably through its ability to block CNS alpha-noradrenergic receptors and consequently CNS regulation of anterior pituitary function. In the present study, we determined whether a chlordimeform-induced delay in the ovulatory surge of LH would alter pregnancy outcome in intact females. Chlordimeform (50 mg/kg) or sodium pentobarbital (35 mg/kg), as a positive control, was administered in order to delay ovulation 24 (1-day delay) or 48 hr (2-day delay). Females were then housed with proven fertile males on the evening of proestrus (0-day delay group), the following evening (1-day delay group), or the evening after that (2-day delay group). The number of receptive females in each group, the mean lordosis quotient, and the number of sperm-positive females in each group were recorded. All females were killed on Gestation Day 20. The number of pregnant females in the 1- or 2-day delay groups was reduced with both chlordimeform and pentobarbital. Also, delaying ovulation for 1 or 2 days with either compound resulted in a significant reduction in the number of live pups present on Gestation Day 20 and a decrease in the number of implantation sites. Litter size was not affected if the females were mated on the same day that treatment was administered (0-day delay).(ABSTRACT TRUNCATED AT 250 WORDS)
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The objective quantification of drusen (and other macular lesions) should have applications epidemiologically, in the study of the natural history of drusen, and with such instruments as the scanning laser ophthalmoscope. The automated extraction of drusen from photographs is technically difficult because of uneven macular reflectance, and the confusing pattern of darker vessels. We have developed a method using an IBM personal computer, an image digitising board and specially written software. Once the image is digitised, no further input from the operator is necessary. We present the results of manual counting versus automated counting on a small series of patients with drusen. The automated technique is highly reproducible, and will calculate the retinal area occupied by drusen. The area and numbers of drusen can be compared over time, giving an index of progression. Hard drusen are fairly well detected, but the detection of soft drusen with their lower contrast remains a problem. The technique cannot distinguish between drusen and other pale lesions (e.g., atrophic retinal changes).
A modified open mask system incorporating an en face air jet to dry the target area during ablation and a conjunctival plication mechanism, which allows ab externo delivery of the 193 nm excimer laser without prior conjunctival dissection, has been developed to form small bore sclerostomies accurately and atraumatically. Full thickness sclerostomies, and sclerostomies guarded by a smaller internal ostium can be created. A pilot therapeutic trial was conducted in pseudophakic patients with advanced open angle glaucoma. Six full thickness sclerostomies (200 microns and 400 microns diameter) and three guarded sclerostomies were created in nine patients by 193 nm excimer laser ablation (fluence per pulse 400 mJ/cm2, pulse rate 16 Hz, air jet pressure intraocular pressure +25 mm Hg). After 6 months' follow up, intraocular pressure was controlled (< or = 16 mm Hg) in eight of the nine patients (6/9 without medication). Early postoperative complications included hyphaema (trace--2.5 mm) (6/9), temporary fibrinous sclerostomy occlusion (4/9), profound early hypotony (all patients without fibrinous occlusion), and suprachoroidal haemorrhage in one case. Conjunctival laser wounds were self sealing. Small bore laser sclerostomy procedures are functionally equivalent to conventional full thickness procedures, producing early postoperative hypotony, with an increased risk of suprachoroidal haemorrhage in association with this. Further research is required to improve control over internal guarding in excimer laser sclerostomy before clinical trials of this technique can safely proceed.
The formamidine pesticide chlordimeform (CDF) has been found to interfere with the hormonal control of ovulation in the rat by a presumptive disruption in the catecholaminergic regulation of the midcycle surge of luteinizing hormone (LH). While the brain hypothalamic mechanisms underlying generation of the hamster surge have not been as well-defined, there is evidence for an adrenergic component. The present experiments were designed to investigate the effects of CDF on ovulation in the golden hamster and whether any observed alterations are associated with differences in the appearance of the surge. Intraperitoneal CDF injections (0, 75, 150, or 200 mg/kg) at 1400 hr on proestrus caused a dose-related reduction in oocytes retrieved at 0700 hr on the day of estrus. Additional experiments demonstrated that this effect was due to a delay in ovulation and not a decrease in the complement of oocytes released. Doses of 150 or 200 mg/kg at 1100 hr or 200 mg/kg at 1600 hr were without a comparable ovulatory effect. Characterization of the LH surge indicated that there was a dose-related delay, but that this effect was not sufficient to account for the delay in ovulation. Animals dosed at 1100 hr (150 or 200 mg/kg) exhibited shifts in the surge identical to those animals injected at 1400 hr, but did not show any such detectable effects on the time of oocyte release. CDF administered at 1100 or 1400 hr also caused alterations in serum estradiol and progesterone, even at a relatively low dose of 37.5 mg/kg. The results indicate that CDF given at a time just prior to the preovulatory rise in LH is able to impede ovulation in the hamster by possibly influencing some ovulatory event(s) triggered by the surge. Also, the ability of CDF to alter the timing of LH release is consistent with catecholaminergic participation in the generation of the gonadotropin signal stimulating the final events leading to ovulation. Under the present conditions, this perturbation can be characterized as a delay in the LH trigger, rather than a blockade.
Excimer laser sclerostomy is a new glaucoma filtration procedure in which the argon fluoride excimer laser at 193 nm is delivered ab externo through a modified open mask system incorporating an en-face air jet to dry the target area and preserve hemostasis during ablation and a conjunctival plication mechanism, which allows the conjunctival and scleral wounds created by through-and-through ablation to separate once the mask is removed. No preparatory dissection of the conjunctiva is required. Five 200-microns and five 500-microns sclerostomies were formed by ablation at a pulse repetition rate of 20 Hz and a fluence per pulse of 400 mJ/cm2 in fellow eyes of five rhesus monkeys with experimental glaucoma. Overall, seven of the ten eyes attained a functional result, with intraocular pressures remaining below 21 mmHg for 6 +/- 1 days and rising to the pre-operative level after 10 +/- 3 days without adjunctive antifibroblast medication. The duration of filtration for 200-microns and 500-microns sclerostomies was similar, and parallels that previously observed for posterior lip sclerectomy in the same animal model. The three eyes with no functional result all had incorrectly positioned sclerostomies. Choroidal detachment and significant shallowing of the anterior chamber did not occur. Excimer laser sclerostomy appears to be a viable technique for filtration, provided that mask placement is accurate.
The argon fluoride (ArF) excimer laser at 193 nm ablates the ocular tissues with a new order of precision and virtually no adjacent damage. A glaucoma filtration operation has been designed in which small-bore sclerostomies are created using the ArF excimer laser delivered through an open mask. The mask plicates the conjunctiva at the limbus prior to ablation. Removing the mask at the end of the procedure allows the conjunctiva to relax back to its original position, separating the conjunctival and scleral wounds. Formal conjunctival dissection is thus avoided. Feasibility studies in cadaver pig eyes, using a fluence per pulse of 400 mJ/cm2 and a pulse repetition rate of 20 Hz, indicate that sclerostomies of 300 microns diameter can be reliably formed if an en-face air jet is built into the mask to raise the pressure in the target area, preventing aqueous flooding.
The red-free negatives of 53 right eyes (30 normal eyes and 23 glaucomatous eyes) and 51 left eyes (32 normal eyes and 19 glaucomatous eyes) were analysed using two different image densitometry techniques. The first technique measured the density from rectangular sample areas, while the second measured density from sector-shaped sample areas which more closely follow the course of the nerve fibres in the retina. Indices which measured the deviation of the data from a clinically determined normal 'gold standard' were calculated, and were used to determine the optimum sensitivity and specificity in separating normal from glaucomatous eyes. There is a significant difference between the data from the normal and glaucomatous groups of eyes, when measured from the sector sample areas. The relative efficacy of this technique is also shown by the improved values of sensitivity (from 42%-70% to 70%-91%), although specificity remained fairly constant (from 66%-83% to 62%-88%).
To investigate the etiology of nasopharyngeal secretion reflux under anesthesia, which could contaminate the conjunctiva, we photographed, after preoperative nasal instillation of fluorescein, the faces of 224 consecutive patients having cataract surgery under general (n = 78) and local (n = 146) anesthesia. In 10 patients, extension of the neck and facial contour caused fluid to drain from the nose directly into the conjunctival cul-de-sac. Nine of the 78 patients under general anesthesia had nasal secretions on the face at the end of surgery, usually due to leaking around the endotracheal tube. Adjusting head posture by moderate neck flexion and taking care to prevent leakage around the endotracheal tube, together with antiseptic preparation of the nose, may prevent contamination of the operative field by nasal secretions.
The aim of our experiments has been to analyse how formation of chemical synapses affects the distribution of calcium (Ca2+) currents and neurite outgrowth of leech Retzius cells. Previous results showed that Ca2+ currents measured in the initial process or 'stump' of postsynaptic cells were significantly smaller than those in corresponding sites on presynaptic neurons. In the present experiments, neurons were plated together in close apposition as pairs or as triads, with the tip of one Retzius cell touching the soma of another. Ca2+ currents from selected areas of the neuronal surfaces were measured by loose-patch recording before and after the formation of chemically mediated synaptic connections, which developed in about 8 h. With three cells arranged in a row, the last of the series, which was purely postsynaptic (i.e. with no target), also showed a dramatic reduction in Ca2+ currents in its initial segment, compared with the currents seen in either the first cell (purely presynaptic) or the second cell of the chain (which was both postsynaptic to the first cell and presynaptic to the third). This suggests that retrograde as well as anterograde effects on Ca2+ currents occurred as a result of synapse formation: the Ca2+ currents in the middle cell did not decrease although a synapse had been formed on it. To test for additional consequences of synapse formation, neurite outgrowth was measured in postsynaptic cells and in single cells plated on an extract of extracellular matrix containing laminin (ECM-laminin). After 48 h, the total length of neuritic outgrowth in postsynaptic cells was only about one third of that in single cells.(ABSTRACT TRUNCATED AT 250 WORDS)