Generation of antibody diversity before and after immunization.
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Biomedical subjects
Publications and source records attributed to N S Levy.
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Vitamin A deficiency was produced in mice and was used to investigate the role of vitamin A in immune function. Cellular immunity, as measured by delayed-type hypersensitivity, diminished in early deficiency before weight and appetite changes occurred and declined further as the deficiency progressed. Humoral immunity, as measured by serum immunoglobulin M (IgM) responses to a protein antigen (hemocyanin), also declined. The kinetics of antibody production were unaffected by the deficiency. The T-cell number remained unchanged, but B-cell and macrophage numbers were increased in vitamin A--deficient mice. Surface expression of membrane glycoproteins (Thy-1, Lyt-1, Lyt-2, L3T4, IgM, Mac-1) was unchanged by the deficiency, as were lymphocyte numbers and distribution. The results suggest that vitamin A deficiency is associated with a functional immune system defect.
A detailed analysis of the genes and proteins that participate in the murine immune response to PC has provided key insights at the structural level into the phenomenon of somatic mutation in B cells. Most anti-PC antibodies are encoded by 1 VH gene of the S107 subfamily, and 3 VK genes, VKT15 of the VK22 subfamily, VKM3 from the VK8 subfamily, and VK167 from the VK24 subfamily. No mutation was detected in these genes until the 2nd wk after immunization, indicating that mutation is under developmental control. The protein sequences of 73 heavy and light chains derived from the secondary response support the concept of developmental activation of mutation after antigen stimulation. No mutation was found in the IgM antibodies, whereas half of the IgG and IgA antibodies had mutation. Most of the mutated antibodies had higher affinity for antigen than their germline counterparts, which suggests that the major role of somatic mutation is to increase affinity rather than to create new specificities. Nucleotide sequencing established two hallmarks of mutation in immunoglobulin genes: mutations are targeted to a 1 kilobase region surrounding and including the rearranged variable gene, and they occur at an extraordinary frequency of 10(-2) nucleotide substitutions. Mutation is probably caused by DNA repair, and may occur during error-prone repair of nicked DNA around the variable gene or during mismatch repair of misaligned structural intermediates. The elucidation of this remarkable mechanism clearly requires studies of a more dynamic character. Two major questions that need to be answered are: what targets mutation to the variable gene, and what enzymes are involved?
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Goldmann kinetic perimetry is a commonly used measurement of visual field defects in open-angle glaucoma. The many new automated perimeters should be assessed against this common standard with a view to comparing their sensitivity in making clinical judgments of the presence and extent of a visual field defect. This study compares the Coopervision Dicon 2000 perimeter and its automated two-zone suprathreshold program with Goldmann kinetic perimetry in 26 patients with open-angle glaucoma. The two-zone suprathreshold testing program on the Coopervision Dicon perimeter was found to be at least as sensitive as the Goldmann kinetic perimeter in identifying the presence and extent of visual field defects in open-angle glaucoma.
Mechanical movement, reflecting compression within the lamina cribrosa, has been suggested as an initiating event in the production of damage in glaucoma. Reversible movements within the lamina cribrosa were sought and studied by characterizing the displacement of fine platinum wire following short-term elevation of intraocular pressure in 13 enucleated human eyes. With IOP elevation, maximum movement in the optic nerve occurred near its center, with minimum movement at its periphery. The difference in movement between these two locations increased with increases in IOP. However, the greatest displacement per unit of IOP elevation occurred at the lowest IOP. Resistance to further displacement occurred as higher IOP was reached. The differential mechanical displacement observed may initiate damage in open-angle glaucoma by causing compression of the vessels and/or shearing of axons within the lamina cribrosa.
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Mechanical compression of axons within the lamina scleralis has been suggested as a mechanism of damage in glaucoma. Movement within the optic nerve head was studied after acute intraocular pressure elevation in the enucleated primate eye. Fine platinum wire was positioned with the lamina scleralis and displacement characterized after IOP elevation. These studies demonstrate the following: (1) retrodisplacement increases significantly with increasing pressure, (2) maximum retrodisplacement occurs at the center and minimum retrodisplacement occurs at the periphery of the optic nerve, (3) retrodisplacement at the position of minimum movement in the optic nerve is indistinguishable from that in the sclera, (4) 67% of the net retrodisplacement occurs after a 15-mm Hg increase in IOP, and (5) tangential displacements within the lamina scleralis also increase with increasing pressure but are only 50% of the magnitude of retrodisplacements.
Our study indicates that by using data obtained from the Model 3000 Echo-Oculometer, 93% of eyes receiving intraocular lenses will have an optimal visual acuity which will differ by less than three diopters from that calculated. With oscilloscopic control of the end points, the Echo-Oculometer provided good inter-observer reproducibility and low variability.
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To determine whether retinal abnormalities occur in patients with chronic pancreatitis, ophthalmoscopic and retinal-function evaluation was performed in 28 patients with chronic pancreatitis and 19 healthy subjects. The final threshold of dark adaptation was significantly increased 40 per cent (P less than 0.001) in patients with pancreatitis, whether or not they had steatorrhea. Patients with steatorrhea had a significant decrease of about 42 per cent (P less than 0.001) in the b-wave of the electroretinogram, a measure of both rod and cone function. Seven of the 28 patients complained of difficulty with hight vision; six of these seven had morphologic lesions on ophthalmoscopic examination, confirmed by fluorescein angiography. No correlation was found between any of the retinal abnormalities and the serum vitamin A or zinc levels or glucose tolerance. Non-diabetic retinal lesions and retinal-function abnormalities are common in patients with chronic pancreatitis, even in the absence of steatorrhea.
A 5-month-old girl with retinitis pigmentosa was the healthy offspring of a family with progressive autosomal dominant retinitis pigmentosa. Serial evaluation by both electroretinograph and ophthalmoscopy over a four-year period confirmed the diagnosis and indicated that as early as 5 months of age, electroretinographic abnormalities were present in the patient. These consisted of a reduction in the dark-adapted b-wave amplitude, prominent X-wave, and no suppression of the second b-wave response to paired light stimuli at 75 msec. Progressive reduction in the scotopic electroretinography amplitude has occurred over the ensuing four years, although light-adapted (cone) function still appears normal. Clinical evidence of retinitis pigmentosa became apparent only late in the patient's third year when fine peripheral pigment clumping and vessel attentuation could be seen.
The monocularly elicited transscleral visual evoked cortical response was measured in a group of patients with asymmetric visual field loss due to chronic open-angle glaucoma. It was established that the visual field loss in the 2 eyes was statistically different in the patients. In addition, the peak amplitude of the visual evoked response obtained from a common occipital cortical position was statistically different when the 2 eyes were separately stimulated. A good linear correlation was found between the amplitude of the monocular transscleral visual evoked response and the amount of visual field remaining on tangent screen perimetry. The best correlation was found when a red stimulus was used to elicit the VER. The monocularly elicited visual evoked response provides an objective measurement of visual field in chronic open-angle glaucoma. It has value in those patients who have asymmetric disease and who are unable to provide reliable subjective responses. It may be useful in such patients to follow progression of the glaucomatous process.
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Thirty measurements of intraocular pressure (IOP) were performed on 10 children either with congenital or secondary glaucoma, before and after halothane anesthesia. In 7 normal eyes, IOP decreased a mean of 3 mm Hg, while in 23 glaucomatous eyes, mean IOP decreased from 43 to 34 mm Hg. In 5 of the 23 glaucomatous eyes, IOP decreased below 25 mm Hg and in only one patient below 21 mm Hg. Our findings indicate that an abnormally elevated IOP during halothane anesthesia suggests a glaucomatous process. A normal IOP during halothane does not absolutely preclude the absence of glaucoma. Intraocular pressure greater than 21 mm Hg during halothane anesthesia should be viewed with suspicion when coupled with other clinical observations of pathologic significance. Awake, sedated IOP measurements appeared to provide a reliable index of glaucoma in the population studied.
The effect of controlled systemic hypotension on intraocular pressure (IOP) and visual function was measured in a group of 12 patients undergoing extracorporeal perfusion during cardiovascular surgery. When venous pressure was controlled, intraocular pressure was noted to fall following a fall in the systemic blood pressure. There was a return of IOP toward normal levels with recovery of the systemic blood pressure. Systemic hypotension of 25 to 100 mm Hg for up to 201 minutes in the presence of hemodilution and hypothermia was not associated with any functional or morphologic change in ocular function.
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A group of 238 patients with cerebral palsy were identified of whom 108 could be studied through their charts. Only 20 of these patients had strabismus. Of this group, 10 received no surgical therapy. In these patients followed up to a period of four years, no evidence of significant change in the strabismic deviation was found. Patients who were treated by medical and optical means alone did not show evidence of improvement. Surgical therapy was effective in providing a cosmetically acceptable result. Surgery was performed between two and one-half and 13 years of age in eight patients, with an average age of surgery of 6.5 years. The results which we obtained are comparable to those obtained by others at an earlier age. It does not appear that the age of surgery affects the ultimate cosmetic nor functional outcome in children with cerebral palsy.