Josef Eisinger | Mount Sinai School of Medicine (original) (raw)

Papers by Josef Eisinger

Research paper thumbnail of Precipitation of synthetic polynucleotides by Mg2+

Research paper thumbnail of Lead and wine. Eberhard Gockel and the colica Pictonum

Medical History, 1982

Thecolica Pictonum or colic of Poitou, under these and many other names, was a frequent, widespre... more Thecolica Pictonum or colic of Poitou, under these and many other names, was a frequent, widespread, and deadly disease from Roman times until the eighteenth century. Its unique pathognomonic, notably a severe colic succeeded by paralysis and other central nervous system dysfunction, makes it possible to identify the disease with certainty as chronic lead disease, usually caused by the ingestion of lead-adulterated wines. The custom of sweetening and preserving sour wines with lead-containing additives is traced to the Romans. They had made the empirical discovery that sapa, a syrup prepared by concentrating must in a lead vessel, kept wine from spoiling and that it had, moreover, an agreeable flavour.Reports of outbreaks of the colica Pictonum appear in the medical literature from Roman times, but the correct aetiology of the disease was not discovered until the seventeenth century following a series of outbreaks in Southern Germany which were related to unfavourable climatic and political conditions. The connexion between the disease and prevailing methods for "correcting" wines was drawn in 1696 by Eberhard Gockel, then the city physician of Ulm. This achievement can be traced to his familiarity with Samuel Stockhausen's work on plumbism among miners and potters, as well as to the favourable epidemiological situation presented by Gockel's monastic patients. From the literary evidence assembled here and from experimental determinations of the lead content of sapa and similar concentrates, it is possible to estimate the lead levels and toxicity of wines from various eras. The levels range up to 80 mg/l and make it apparent that many wines were sufficiently toxic to account for the incidence and severity of the colica Pictonum. Explanations for the disastrous persistence of the colic of Poitou are discussed, as are the similarities between Gockel's approach and the methods of modern environmental medicine.

Research paper thumbnail of Additions and Corrections - Synthetic Spectroscopic Models Related to Coenzymes and Base Pairs. II. Evidence for Intramolecular Base-Base Interactions in Dinucleotide Analogs

Journal of the American Chemical Society, 1969

Research paper thumbnail of The anticodon-anticodon complex

Journal of Molecular Biology, 1974

ABSTRACT

Research paper thumbnail of Interpretation of intramolecular energy transfer experiments

Journal of Molecular Biology, 1974

... J. Mol. Biol. 77, 223235. LETTERS TO THE EDITOR 647 Dale, RE Eisinger, J. (1974). In Concepts... more ... J. Mol. Biol. 77, 223235. LETTERS TO THE EDITOR 647 Dale, RE Eisinger, J. (1974). In Concepts m Biochemical Fluorescence (Chen, RF Edelhoch, H., eds), Marcel Dekker, New York, m the press. Eisinger, J. (1969). Biochemistry, 8, 39023908. Forster, Th. (1951). ...

Research paper thumbnail of Fluorometry of absorbant and turbid samples and the lateral mobility in membranes of intact erythrocytes

Journal of Luminescence, 1984

ABSTRACT Intrinsic and extrinsic fluorophores attached to large biological assemblies (e.g. cells... more ABSTRACT Intrinsic and extrinsic fluorophores attached to large biological assemblies (e.g. cells) find many useful applications in biophysics and medical science. Since such samples frequently absorb and/or scatter light strongly, special techniques have been developed for dealing with the artifacts which result. The use of excimerization probes as indicators of the local lateral mobility in the membranes of intact red blood cells provides an illustration.

Research paper thumbnail of Lead Poisoning From Cocktail Glasses

JAMA: The Journal of the American Medical Association, 1977

Report of Cases A 53-year-old geophysicist entered the coronary care unit for investigation of pr... more Report of Cases A 53-year-old geophysicist entered the coronary care unit for investigation of progressively severe precordial pain of three weeks' duration. He also complained of fatigue and constipation. For eight years, he had received methyldopa, 1 gm daily, as ...

Research paper thumbnail of Biochemistry and measurement of environmental lead intoxication

Quarterly reviews of biophysics, 1978

Research paper thumbnail of Binding constants from zone transport of interacting molecules

Biochemistry, 1973

ABSTRACT

Research paper thumbnail of Visible gel electrophoresis and the determination of association constants

Biochemical and Biophysical Research Communications, 1971

Research paper thumbnail of Fluorimetric apparatus and method for analysis of body fluid

Research paper thumbnail of Rapid Fluorometric Assay of Bilirubin and Bilirubin Binding Capacity in Blood of Jaundiced Neonates: Comparisons with Other Methods

Pediatrics, Sep 1, 1980

The concentrations of total blood bilirubin, albumin-bound bilirubin, and the reserve and total b... more The concentrations of total blood bilirubin, albumin-bound bilirubin, and the reserve and total bilirubin binding capacities of 35 neonatal blood samples (28 patients) were determined by automated front-face fluorometry ((hematofluorometer). These values were compared to results of diazo determinations, Sephadex gel filtration, and peroxidase-oxidation methods. Total blood bilirubin level by fluorometry agreed well with the total plasma bilirubin level by diazotization (r = .96, sigma = 1.7 mg/100 ml). Albumin-bound bilirubin concentrations by fluorometry also correlated well with diazo values (r = .95, sigma = 1.9 mg/100 ml) and were slightly lower than the total blood bilirubin concentrations. Values for total bilirubin binding capacity determined by fluorometry agreed well with results obtained for the same specimens by Sephadex gel filtration (n = 28, r = .97, sigma = 1.8 mg/100 ml) and by peroxidase-catalyzed oxidation (n = 25, r = .97, sigma = 1.7 mg/100 ml). The agreement among the results obtained by the three methods indicates a well-defined in vitro end point at which available primary or "tight" binding sites on albumin are saturated with bilirubin. In this clinical experience the coefficient of variation of results with the hematofluorometer was 8.4% for total blood bilirubin and 6.5% for total binding capacity. A comparison of "sick" with "well" infants revealed that the fraction of bilirubin not bound to albumin was significantly different for these two groups. The assays made with the hematofluorometer are quick (10 to 15 minutes) and require only a small quantity (approximately 150 microliters) of blood.

Research paper thumbnail of Triplet state of DNA

The Journal of Chemical Physics

Additional proof has been obtained for the fact that the triplet state in DNA and poly dAT reside... more Additional proof has been obtained for the fact that the triplet state in DNA and poly dAT resides at the thymine residue by comparing the intensities of the triplet ESR and phosphorescence signals from DNA's from various sources having different (A+T)∕(G+C) ratios. The TMP triplet which is not populated from the exited singlet state in dilute neutral solutions can be

Research paper thumbnail of Luminescence and binding studies on tRNA-Phe

Proceedings of the National Academy of Sciences

The phenylalanine transfer RNA of baker's yeast (tRNAPhe) contains a base Y of unknown molecular ... more The phenylalanine transfer RNA of baker's yeast (tRNAPhe) contains a base Y of unknown molecular structure next to the anticodon triplet. Since the base Y fluoresces at room temperature (Xmax = 431 nm), its emission properties offer a unique tool for studying conformational and binding properties of tRNAPhe. The results obtained by these experiments include the following:

Research paper thumbnail of Quantitative determination of erythrocyte zinc protoporphyrin

Journal of Laboratory and Clinical Medicine

An elevated zinc protoporphyrin (ZPP) level in blood is indicative of lead poisoning (as well as ... more An elevated zinc protoporphyrin (ZPP) level in blood is indicative of lead poisoning (as well as iron-deficiency anemia) and is the basis for certain fluorometric screening tests. The calibration of such test protocols and instruments requires ways to reliably determine absolute ZPP concentrations in blood. Two such methods are described: one is an ethanol extraction method and the other a fluorometric addition method using detergent hemolyzed blood. A careful determination of the molar extinction coefficient of ZPP gives EmM=161 in pyridine. Corrections are offered for a previously published protocol for determining the ZPP concentration from the fluorescence intensity of diluted blood. The choice of units for expressing the ZPP concentration in blood is discussed, as is the absorbance correction in quantitative fluorometry of samples which are not optically thin at the excitation wavelength.

Research paper thumbnail of Zinc Protoporphyrin Level in Blood Determined by a Portable Hematofluorometer: A Screening Device for Lead Poisoning

Journal of Laboratory and Clinical Medicine

An inexpensive portable fluorometer has been designed which can be used to determine the concentr... more An inexpensive portable fluorometer has been designed which can be used to determine the concentration of zinc protoporphyrin (ZPP) in a drop of unprocessed blood deposited on a disposable glass slide. No volume measurement of the blood sample need be made. The instrument displays the ZPP level in micrograms per deciliter of blood accurately and reproducibly, automatically calibrating each determination by comparing the blood fluorescence with that of a stable dye. The instrument, which we call a hematofluorometer, is ideally suited for use in primary screening for childhood and occupational lead intoxication. It can be used by public health personnel after a few minutes of instruction. Comparisons of ZPP levels obtained with the use of the hematofluorometer with erythrocyte protoporphyrin levels obtained using accepted extraction methods are presented.

Research paper thumbnail of Zinc protoporphyrin in blood as a biological indicator of chrome lead intoxication

Journal of environmental pathology and toxicology

Traditionally, the diagnosis of lead intoxication has relied upon blood lead and urine lead deter... more Traditionally, the diagnosis of lead intoxication has relied upon blood lead and urine lead determinations. However, metabolic changes in the biosynthetic pathway of heme as well as damage in other organ systems may occur at blood lead levels hitherto regarded as "safe." Lead intoxication leads to elevated zinc protoporphyrin (ZPP) levels in the blood which can be measured quickly, inexpensively and conveniently on a drop of unprocessed whole blood by means of a dedicated front face fluorometer, called a hematofluorometer. In the present study, ZPP showed a strong correlation with the lead-in-blood level, as well as with signs and symptoms of lead-related disease. It is concluded that zinc protoporphyrin determination offers a preferred primary screening test for lead-exposed populations.

Research paper thumbnail of Distribution of erythrocyte free porphyrin content in erythropoietic protoporphyria

Journal of Laboratory and Clinical Medicine

Erythrocytes of patients suffering from erythropoietic protoporphyria (EPP) contain high levels o... more Erythrocytes of patients suffering from erythropoietic protoporphyria (EPP) contain high levels of unchelated protoporphyrin IX (PP) molecules when they enter circulation, and the leakage of PP that leaks from the circulating cells is responsible for the patients' cutaneous photosensitivity. The level of PP in EPP blood has long been used as an indicator of the severity of the disease and is useful in its management. The present study investigates what additional information may be obtained by determining the distribution of the PP content of individual EPP red cells. Absorption and fluorescence images of fields of the dispersed and immobilized red cells from nine patients with EPP were acquired under computer control by use of an inverted fluorescence microscope equipped with a cooled slow-scan charge-coupled device camera. The distribution functions of the fluorescence emitted by individual red blood cells (IRBC) were derived by a suitable image analysis program and were conve...

Research paper thumbnail of A rapid fluorometric method for determining bilirubin levels and binding in the blood of neonates: comparisons with a diazo method and with 2-(4'-hydroxybenzene)azobenzoic acid dye binding

Pediatrics, 1980

A simple, rapid fluorometric method for determining the albumin-bound bilirubin concentration, to... more A simple, rapid fluorometric method for determining the albumin-bound bilirubin concentration, total blood bilirubin concentration, and the bilirubin reserve-binding capacity of albumin was clinically evaluated using blood specimens from 79 neonates. This study showed that these bilirubin determinations, made by means of the Bell Laboratories hematofluorometer, correlated well with plasma bilirubin levels obtained by a diazotization (Jendrassik-Grof) method. Hematofluorometer reserve-binding capacities correlated very well with 2-(4'-hydroxybenzene)azobenzoic acid (HABA) dye reserve-binding capacities for specimens of artificially jaundiced adult blood. For specimens of neonatal blood the HABA dye reserve capacity was, on the average, higher than the hematofluorometer reserve-binding capacity, particularly for specimens from low-birth-weight babies (less than 2,000 gm). Comparison of HABA reserve capacity and hematofluorometer reserve capacity for high-birth-weight babies (great...

Research paper thumbnail of Erythrocyte protoporphyrin/heme ratio by hematofluorometry

Research paper thumbnail of Precipitation of synthetic polynucleotides by Mg2+

Research paper thumbnail of Lead and wine. Eberhard Gockel and the colica Pictonum

Medical History, 1982

Thecolica Pictonum or colic of Poitou, under these and many other names, was a frequent, widespre... more Thecolica Pictonum or colic of Poitou, under these and many other names, was a frequent, widespread, and deadly disease from Roman times until the eighteenth century. Its unique pathognomonic, notably a severe colic succeeded by paralysis and other central nervous system dysfunction, makes it possible to identify the disease with certainty as chronic lead disease, usually caused by the ingestion of lead-adulterated wines. The custom of sweetening and preserving sour wines with lead-containing additives is traced to the Romans. They had made the empirical discovery that sapa, a syrup prepared by concentrating must in a lead vessel, kept wine from spoiling and that it had, moreover, an agreeable flavour.Reports of outbreaks of the colica Pictonum appear in the medical literature from Roman times, but the correct aetiology of the disease was not discovered until the seventeenth century following a series of outbreaks in Southern Germany which were related to unfavourable climatic and political conditions. The connexion between the disease and prevailing methods for "correcting" wines was drawn in 1696 by Eberhard Gockel, then the city physician of Ulm. This achievement can be traced to his familiarity with Samuel Stockhausen's work on plumbism among miners and potters, as well as to the favourable epidemiological situation presented by Gockel's monastic patients. From the literary evidence assembled here and from experimental determinations of the lead content of sapa and similar concentrates, it is possible to estimate the lead levels and toxicity of wines from various eras. The levels range up to 80 mg/l and make it apparent that many wines were sufficiently toxic to account for the incidence and severity of the colica Pictonum. Explanations for the disastrous persistence of the colic of Poitou are discussed, as are the similarities between Gockel's approach and the methods of modern environmental medicine.

Research paper thumbnail of Additions and Corrections - Synthetic Spectroscopic Models Related to Coenzymes and Base Pairs. II. Evidence for Intramolecular Base-Base Interactions in Dinucleotide Analogs

Journal of the American Chemical Society, 1969

Research paper thumbnail of The anticodon-anticodon complex

Journal of Molecular Biology, 1974

ABSTRACT

Research paper thumbnail of Interpretation of intramolecular energy transfer experiments

Journal of Molecular Biology, 1974

... J. Mol. Biol. 77, 223235. LETTERS TO THE EDITOR 647 Dale, RE Eisinger, J. (1974). In Concepts... more ... J. Mol. Biol. 77, 223235. LETTERS TO THE EDITOR 647 Dale, RE Eisinger, J. (1974). In Concepts m Biochemical Fluorescence (Chen, RF Edelhoch, H., eds), Marcel Dekker, New York, m the press. Eisinger, J. (1969). Biochemistry, 8, 39023908. Forster, Th. (1951). ...

Research paper thumbnail of Fluorometry of absorbant and turbid samples and the lateral mobility in membranes of intact erythrocytes

Journal of Luminescence, 1984

ABSTRACT Intrinsic and extrinsic fluorophores attached to large biological assemblies (e.g. cells... more ABSTRACT Intrinsic and extrinsic fluorophores attached to large biological assemblies (e.g. cells) find many useful applications in biophysics and medical science. Since such samples frequently absorb and/or scatter light strongly, special techniques have been developed for dealing with the artifacts which result. The use of excimerization probes as indicators of the local lateral mobility in the membranes of intact red blood cells provides an illustration.

Research paper thumbnail of Lead Poisoning From Cocktail Glasses

JAMA: The Journal of the American Medical Association, 1977

Report of Cases A 53-year-old geophysicist entered the coronary care unit for investigation of pr... more Report of Cases A 53-year-old geophysicist entered the coronary care unit for investigation of progressively severe precordial pain of three weeks' duration. He also complained of fatigue and constipation. For eight years, he had received methyldopa, 1 gm daily, as ...

Research paper thumbnail of Biochemistry and measurement of environmental lead intoxication

Quarterly reviews of biophysics, 1978

Research paper thumbnail of Binding constants from zone transport of interacting molecules

Biochemistry, 1973

ABSTRACT

Research paper thumbnail of Visible gel electrophoresis and the determination of association constants

Biochemical and Biophysical Research Communications, 1971

Research paper thumbnail of Fluorimetric apparatus and method for analysis of body fluid

Research paper thumbnail of Rapid Fluorometric Assay of Bilirubin and Bilirubin Binding Capacity in Blood of Jaundiced Neonates: Comparisons with Other Methods

Pediatrics, Sep 1, 1980

The concentrations of total blood bilirubin, albumin-bound bilirubin, and the reserve and total b... more The concentrations of total blood bilirubin, albumin-bound bilirubin, and the reserve and total bilirubin binding capacities of 35 neonatal blood samples (28 patients) were determined by automated front-face fluorometry ((hematofluorometer). These values were compared to results of diazo determinations, Sephadex gel filtration, and peroxidase-oxidation methods. Total blood bilirubin level by fluorometry agreed well with the total plasma bilirubin level by diazotization (r = .96, sigma = 1.7 mg/100 ml). Albumin-bound bilirubin concentrations by fluorometry also correlated well with diazo values (r = .95, sigma = 1.9 mg/100 ml) and were slightly lower than the total blood bilirubin concentrations. Values for total bilirubin binding capacity determined by fluorometry agreed well with results obtained for the same specimens by Sephadex gel filtration (n = 28, r = .97, sigma = 1.8 mg/100 ml) and by peroxidase-catalyzed oxidation (n = 25, r = .97, sigma = 1.7 mg/100 ml). The agreement among the results obtained by the three methods indicates a well-defined in vitro end point at which available primary or "tight" binding sites on albumin are saturated with bilirubin. In this clinical experience the coefficient of variation of results with the hematofluorometer was 8.4% for total blood bilirubin and 6.5% for total binding capacity. A comparison of "sick" with "well" infants revealed that the fraction of bilirubin not bound to albumin was significantly different for these two groups. The assays made with the hematofluorometer are quick (10 to 15 minutes) and require only a small quantity (approximately 150 microliters) of blood.

Research paper thumbnail of Triplet state of DNA

The Journal of Chemical Physics

Additional proof has been obtained for the fact that the triplet state in DNA and poly dAT reside... more Additional proof has been obtained for the fact that the triplet state in DNA and poly dAT resides at the thymine residue by comparing the intensities of the triplet ESR and phosphorescence signals from DNA's from various sources having different (A+T)∕(G+C) ratios. The TMP triplet which is not populated from the exited singlet state in dilute neutral solutions can be

Research paper thumbnail of Luminescence and binding studies on tRNA-Phe

Proceedings of the National Academy of Sciences

The phenylalanine transfer RNA of baker's yeast (tRNAPhe) contains a base Y of unknown molecular ... more The phenylalanine transfer RNA of baker's yeast (tRNAPhe) contains a base Y of unknown molecular structure next to the anticodon triplet. Since the base Y fluoresces at room temperature (Xmax = 431 nm), its emission properties offer a unique tool for studying conformational and binding properties of tRNAPhe. The results obtained by these experiments include the following:

Research paper thumbnail of Quantitative determination of erythrocyte zinc protoporphyrin

Journal of Laboratory and Clinical Medicine

An elevated zinc protoporphyrin (ZPP) level in blood is indicative of lead poisoning (as well as ... more An elevated zinc protoporphyrin (ZPP) level in blood is indicative of lead poisoning (as well as iron-deficiency anemia) and is the basis for certain fluorometric screening tests. The calibration of such test protocols and instruments requires ways to reliably determine absolute ZPP concentrations in blood. Two such methods are described: one is an ethanol extraction method and the other a fluorometric addition method using detergent hemolyzed blood. A careful determination of the molar extinction coefficient of ZPP gives EmM=161 in pyridine. Corrections are offered for a previously published protocol for determining the ZPP concentration from the fluorescence intensity of diluted blood. The choice of units for expressing the ZPP concentration in blood is discussed, as is the absorbance correction in quantitative fluorometry of samples which are not optically thin at the excitation wavelength.

Research paper thumbnail of Zinc Protoporphyrin Level in Blood Determined by a Portable Hematofluorometer: A Screening Device for Lead Poisoning

Journal of Laboratory and Clinical Medicine

An inexpensive portable fluorometer has been designed which can be used to determine the concentr... more An inexpensive portable fluorometer has been designed which can be used to determine the concentration of zinc protoporphyrin (ZPP) in a drop of unprocessed blood deposited on a disposable glass slide. No volume measurement of the blood sample need be made. The instrument displays the ZPP level in micrograms per deciliter of blood accurately and reproducibly, automatically calibrating each determination by comparing the blood fluorescence with that of a stable dye. The instrument, which we call a hematofluorometer, is ideally suited for use in primary screening for childhood and occupational lead intoxication. It can be used by public health personnel after a few minutes of instruction. Comparisons of ZPP levels obtained with the use of the hematofluorometer with erythrocyte protoporphyrin levels obtained using accepted extraction methods are presented.

Research paper thumbnail of Zinc protoporphyrin in blood as a biological indicator of chrome lead intoxication

Journal of environmental pathology and toxicology

Traditionally, the diagnosis of lead intoxication has relied upon blood lead and urine lead deter... more Traditionally, the diagnosis of lead intoxication has relied upon blood lead and urine lead determinations. However, metabolic changes in the biosynthetic pathway of heme as well as damage in other organ systems may occur at blood lead levels hitherto regarded as "safe." Lead intoxication leads to elevated zinc protoporphyrin (ZPP) levels in the blood which can be measured quickly, inexpensively and conveniently on a drop of unprocessed whole blood by means of a dedicated front face fluorometer, called a hematofluorometer. In the present study, ZPP showed a strong correlation with the lead-in-blood level, as well as with signs and symptoms of lead-related disease. It is concluded that zinc protoporphyrin determination offers a preferred primary screening test for lead-exposed populations.

Research paper thumbnail of Distribution of erythrocyte free porphyrin content in erythropoietic protoporphyria

Journal of Laboratory and Clinical Medicine

Erythrocytes of patients suffering from erythropoietic protoporphyria (EPP) contain high levels o... more Erythrocytes of patients suffering from erythropoietic protoporphyria (EPP) contain high levels of unchelated protoporphyrin IX (PP) molecules when they enter circulation, and the leakage of PP that leaks from the circulating cells is responsible for the patients' cutaneous photosensitivity. The level of PP in EPP blood has long been used as an indicator of the severity of the disease and is useful in its management. The present study investigates what additional information may be obtained by determining the distribution of the PP content of individual EPP red cells. Absorption and fluorescence images of fields of the dispersed and immobilized red cells from nine patients with EPP were acquired under computer control by use of an inverted fluorescence microscope equipped with a cooled slow-scan charge-coupled device camera. The distribution functions of the fluorescence emitted by individual red blood cells (IRBC) were derived by a suitable image analysis program and were conve...

Research paper thumbnail of A rapid fluorometric method for determining bilirubin levels and binding in the blood of neonates: comparisons with a diazo method and with 2-(4'-hydroxybenzene)azobenzoic acid dye binding

Pediatrics, 1980

A simple, rapid fluorometric method for determining the albumin-bound bilirubin concentration, to... more A simple, rapid fluorometric method for determining the albumin-bound bilirubin concentration, total blood bilirubin concentration, and the bilirubin reserve-binding capacity of albumin was clinically evaluated using blood specimens from 79 neonates. This study showed that these bilirubin determinations, made by means of the Bell Laboratories hematofluorometer, correlated well with plasma bilirubin levels obtained by a diazotization (Jendrassik-Grof) method. Hematofluorometer reserve-binding capacities correlated very well with 2-(4'-hydroxybenzene)azobenzoic acid (HABA) dye reserve-binding capacities for specimens of artificially jaundiced adult blood. For specimens of neonatal blood the HABA dye reserve capacity was, on the average, higher than the hematofluorometer reserve-binding capacity, particularly for specimens from low-birth-weight babies (less than 2,000 gm). Comparison of HABA reserve capacity and hematofluorometer reserve capacity for high-birth-weight babies (great...

Research paper thumbnail of Erythrocyte protoporphyrin/heme ratio by hematofluorometry