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Biomedical subjects

M L Klein

Publications and source records attributed to M L Klein.

At least 73 records · Page 4Linked to original sources
PubMed1990

Isolation and structural characterization of three isoforms of recombinant consensus alpha interferon.

Recombinant DNA-derived consensus alpha interferon was expressed in Escherichia coli and purified. Isoelectric focusing of this purified protein indicated the presence of three isoelectric subforms of pI 6.1, 6.0, and 5.7. These three subforms were preparatively separated by isoelectric focusing using Immobiline polyacrylamide gel and did not exhibit apparent differences in biological activity and tertiary structure. The pI 5.7 subform could also be separated from the pI 6.1 and 6.0 subforms by reverse-phase HPLC. Automated N-terminal amino acid sequence analysis of the pI 6.1 and 6.0 subforms yielded sequences corresponding to the methionyl and des-methionyl forms of the protein, respectively. Sequence analysis of the pI 5.7 subform indicated that its N terminus is blocked. To further determine the structure of the blocking moiety in the pI 5.7 subform, a blocked N-terminal tryptic peptide was isolated from HPLC peptide mapping of the S-carboxymethylated derivative. Results obtained from mass spectroscopic and amino acid analyses of this peptide suggest that it is blocked with an acetyl group at the N-terminal cysteine residue.

Amino Acid Sequence↗
PubMed1989

Bietti's crystalline dystrophy. A clinicopathologic correlative study.

We report the clinical and electrophysiologic findings in three patients with Bietti's crystalline corneal-retinal dystrophy. The initial evaluation in one patient demonstrated diffuse disease involving retinal pigment epithelium and choriocapillaris with severe widespread disturbance of retinal function. The patient's disease progressed greatly from the age of 36 to 47 years. Two brothers had regional involvement of the posterior pole with disturbances of retinal function attributable to localized disease, and there was only mild progression in these patients. A corneal biopsy specimen from the more severely affected patient and biopsy specimens from a patient whose case had been previously reported demonstrated crystals resembling cholesterol or cholesterol ester and complex lipid inclusions in corneal and conjunctival fibroblasts. Similar inclusions were present in circulating lymphocytes, suggesting that Bietti's crystalline corneal-retinal dystrophy may be due to a systemic abnormality of lipid metabolism.

Adult↗
PubMed1989

Macular grid photocoagulation for macular edema in central retinal vein occlusion.

To obtain pilot information regarding possible benefits of photocoagulation grid treatment for macular edema secondary to nonischemic central retinal vein occlusion, records were reviewed for patients who demonstrated well-documented prompt improvement in edema after treatment. In each of the five selected patients who demonstrated this association, macular edema had been present for a minimum of 6 months. Also, preoperative visual acuity was 20/60 or less, good macular capillary perfusion was present on the fluorescein angiogram, and substantial reduction of edema was demonstrated on clinical examination and by decreased leakage and late staining on fluorescein angiography within 8 weeks following treatment. Postoperative visual acuity either improved or remained unchanged for each eye. These results indicate that, in certain eyes, grid photocoagulation can lessen macular edema, thus supporting the rationale for a randomized clinical trial to determine possible benefits of this therapy.

Adult↗
PubMed1989

Growth features of choroidal neovascular membranes in age-related macular degeneration.

The authors studied 80 eyes of patients with choroidal neovascular membranes (CNVMs) associated with age-related macular degeneration between 1982 and 1988. In each case, fluorescein angiography was done on two occasions separated by an interval of 2 days to 11 weeks (average, 13 days) without intervening photocoagulation. Forty-three CNVMs (54%) grew toward the fovea during the interval between fluorescein angiograms, with growth rates ranging from 1 to 24 microns daily (average, 10 microns daily). The CNVM growth was related to the time interval between angiograms (P less than 0.0001), but was not associated with morphologic features of the CNVM. These results reinforce the need for early detection and prompt evaluation of elderly patients with symptoms of CNVMs.

Aged↗
PubMed1988

Structural characterization of recombinant consensus interferon-alpha.

Recombinant consensus interferon-alpha is derived from genetically modified Escherichia coli containing a synthetic gene constructed from a consensus of interferon sequences. The purified and biologically active protein has been subjected to detailed structural characterization including sequence determination and peptide isolation and identification. The homogeneous consensus interferon-alpha preparation contains two chromatographically indistinguishable homologous polypeptides with one containing an extra methionyl residue at the amino terminus. The delineated amino acid sequence of the protein is identical to that expected from the coding sequence of the gene. Correct oxidation of the molecule has been confirmed with two intramolecular disulfide linkages observed at Cys(1)-Cys(99) and Cys(29)-Cys(139).

Amino Acid Sequence↗
PubMed1988

Control of misincorporation of de novo synthesized norleucine into recombinant interleukin-2 in E. coli.

Interleukin-2 produced from a recombinant E. coli was found to contain as much as 19% norleucine in place of methionine in a minimal medium fermentation. Medium supplementation experiments and use of a leucine-requiring mutant host strain indicated the origin of norleucine to be de novo biosynthesis by reactions involving the enzymes of the leucine biosynthetic pathway. The misincorporation was highly suppressed by addition of either L-leucine or L-methionine to the fermentation and completely suppressed by adding both amino acids.

Aminocaproates↗
PubMed1988

Narrow-bore high-performance liquid chromatography of phenylthiocarbamyl amino acids and carboxypeptidase P digestion for protein C-terminal sequence analysis.

Carboxypeptidase P digestion followed by narrow-bore high-performance liquid chromatography of phenylthiocarbamyl amino acids is employed for polypeptide C-terminal end group and sequence determination. Carboxypeptidase P digestion of polypeptides provides specific cleavage of protein C-terminal amino acids. The digestion offers the advantage that it can be carried out in either 10 mM sodium acetate or water at pH 4.0 in the presence of an enzyme activator, Brij-35. The narrow-bore high-performance liquid chromatography of all 20 phenylthiocarbamyl-amino acids has provided quantitative analysis at low picomole levels. This efficient and sensitive procedure is particularly useful for examining in vivo excision of protein C-termini and for verifying the integrity of various protein products produced by recombinant DNA techniques.

Amino Acid Sequence↗
PubMed1988

Niacin maculopathy.

Three patients with niacin-induced visual symptoms had cystoid maculopathy without leakage on fluorescein angiography, and a fourth patient with no fundus abnormality experienced cessation of visual symptoms upon discontinuation of niacin. All four patients had been taking high doses of niacin (3.0-4.5 g daily) before the onset of symptoms. An additional 15 asymptomatic patients who were receiving high doses of oral niacin (1.0-6.0 g daily) for the treatment of hypercholesterolemia were evaluated for evidence of subclinical macular disease. None of these patients had cystic or other significant macular changes. Niacin causes a reversible toxic cystoid maculopathy that occurs in approximately 0.67% of patients taking high doses of the drug. The authors conclude that among patients taking high doses of oral niacin only those who experience visual symptoms need to be ophthalmologically evaluated.

Adult↗
PubMed1988

Results and complications of pneumatic retinopexy.

Fifty-one patients with primary rhegmatogenous retinal detachment (RD) were treated by pneumatic retinopexy. The overall success rate for reattachment with one operation was 63%. Of the 34 phakic eyes, 25 (74%) were reattached; of the 17 aphakic or pseudophakic eyes, seven (41%) were reattached (P less than 0.05). Postoperative complications included the development of new tears (22%), inadequate closure of the original tear, shifting and delayed absorption of subretinal fluid, and opening of previously closed tears. Pneumatic retinopexy is a valuable new technique; however, careful patient selection and postoperative management is required.

Aged↗
PubMed1987

Visual recovery in combined central retinal artery and central retinal vein occlusion.

We observed two patients who had combined central retinal artery occlusion and central retinal vein occlusion with severely reduced visual acuity and characteristic retinal changes. Over the course of several months, visual acuity and ophthalmoscopic appearance returned to normal. Both patients had a transient visual loss before their occlusive events and a mild nonconcurrent central retinal vein occlusion in their fellow eye. There was no evidence of inflammatory, vascular, or myeloproliferative disease.

Female↗
PubMed1987

Choroidal involvement in systemic necrotizing vasculitis.

Wegener's granulomatosis and lymphomatosis are systemic necrotizing vasculitides of unknown cause. We report similar involvement of the choriocapillaris in these two diseases. A presumed choriocapillaritis caused ischemia and infarction of the choriocapillaris-retinal pigment epithelium-outer neurosensory retina complex. Systemic corticosteroid and immunosuppressive agents were successful in controlling systemic disease and preserving useful vision. At the time of this study, one patient had not had a recurrence for 12 years, and the other patient had been asymptomatic for seven years.

Adult↗
PubMed1987

Sensitivities in older eyes with good acuity: cross-sectional norms.

We measured several indices of foveal visual function for a large group of people aged 60 and older. The data reported in this paper are from individuals who had good acuity in each eye and met a number of other criteria for good ocular health. For each index, we described the rate of cross-sectional change with age using linear regression statistics. We found age-related change for eyes having 20/20 or better acuity to exist for several different indices. Sensitivity mediated by the blue-sensitive cones decreased with age, as expected. However, the rate of decrease was faster for females than for males. At least part of the difference was associated with different rates of lenticular change. Absolute sensitivity at long wavelengths also decreased with age, but at the same rate for each sex. Rayleigh color matches changed with age in a manner consistent with underlying age-related decreases of effective foveal cone photopigment density. However, not all indices showed age-dependent changes. For instance, the time constant describing the rate of photopic dark adaptation did not appear to change with age.

Aging↗
PubMed1987

Sensitivities in older eyes with good acuity: eyes whose fellow eye has exudative AMD.

We compared several indices of foveal visual function between two groups of people aged 60 and older. One group was comprised of individuals who had good acuity in one eye, but had a history of exudative aging macular degeneration (AMD) in the other eye. We measured visual function in these individuals' good eyes only. The second group was a normative group; it was comprised of individuals who had good acuity in each eye. None of the eyes which we tested from either group had funduscopic evidence of macular pathology other than macular drusen and/or hypopigmentation. We found that eyes whose fellow eye had suffered from exudative AMD themselves suffered compromised foveal function, even when they retained 20/20 or better acuity. Losses of sensitivity mediated by blue-sensitive cones tended to be greater for 1 degree than for 3 degrees diameter test stimuli. Absolute sensitivity losses at long test wavelengths were probably due to several factors, including decreased effective cone photopigment density. Slow rates of recovery during dark adaptation were associated with the presence of many macular drusen and/or macular hypopigmentation. Eyes whose fellow eye had suffered from exudative AMD had more macular drusen and hypopigmentation than eyes whose fellow eye had not suffered from exudative AMD.

Aging↗
PubMed1986

Maculopathy associated with combination chemotherapy and osmotic opening of the blood-brain barrier.

Eleven patients with intracranial malignant neoplasms underwent hyperosmotic opening of the blood-brain barrier by rapid mannitol infusion via the internal carotid or vertebral artery. Cyclophosphamide was administered intravenously preceding the mannitol infusion and methotrexate was infused after the mannitol via the same artery. Both the mannitol and methotrexate delivered via the carotid artery have direct access to the ipsilateral choroidal and retinal circulations. In these patients, retinal pigment epithelial changes eventually developed ipsilateral to the carotid infusions. The changes probably represent the toxicity of intraarterial methotrexate possibly potentiated by mannitol-induced opening of the blood-retinal barrier. Functional visual loss was minimal and was not a limiting factor with this therapeutic modality.

Adolescent↗
PubMed1986

Abnormal glucose metabolism and parafoveal telangiectasia.

Parafoveal telangiectasia is a microvascular abnormality of the macula that may be developmental or acquired. Twenty-eight patients with this condition and normal fasting blood glucose levels underwent ophthalmologic evaluation and glucose tolerance testing. Bilateral telangiectasia was more frequently associated with laboratory evidence of abnormal glucose metabolism than unilateral disease (five of eight cases vs six of 17 cases). In five of our patients, results of glucose tolerance testing were consistent with diabetes even though fasting blood glucose levels were normal. Right-angle venules, which have been reported to be an important sign of bilateral disease, were also found in unilateral telangiectasia. Unilateral telangiectasia occurs in females as well as males. Glucose tolerance testing should be performed in all patients who have bilateral parafoveal telangiectasia.

Adult↗
PubMed1982

Central retinal artery occlusion without retrobulbar hemorrhage after retrobulbar anesthesia.

Four patients had central retinal artery occlusions after retrobulbar anesthesia with lidocaine HCl was administered before photocoagulation. One of these four had two separate episodes of closure. Only one had permanent visual loss, and none had evidence of retrobulbar hemorrhage. Each patient had a severe hematologic or vascular disorder. We think that direct trauma to the central retinal artery behind the globe, the pharmacologic or compressive effects of the injected solution, or both caused the occlusions in these patients.

Adult↗
PubMed1981

Maculopathy in cynomolgus monkeys. A correlated fluorescein angiographic and ultrastructural study.

Maculae of seven cynomolgus macaque monkeys (Macaca fascicularis) showing abnormalities in color fundus photographs and fluorescein angiograms were studied in serial sections by light and electron microscopy and compared with three eyes without clinically visible defects in the macula. Maculae that showed hyperfluorescent nonleaking window defects showed no drusen or interruptions in the retinal pigment epithelium (RPE). Six of these monkeys had mis-shapen foveal depressions, all showed some degree of photoreceptor degeneration, and one had cells in Bruch's membrane. Bright yellow spots correlated with scattered RPE filled with lipid vacuoles. Shallow RPE elevations correlated with diffuse nonleaking window defects. Patches of RPE deficient in melanin occurred at sites of hyperfluorescence. Quantitative studies showed that maculae with window defects had more lipofuscin and less melanin per RPE cell. Maculae deemed normal by photography showed degenerating photoreceptors.

Animals↗