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Biomedical subjects

L Grossman

Publications and source records attributed to L Grossman.

At least 145 records · Page 8Linked to original sources
PubMed1977

Micrococcus luteus correndonucleases. III. Evidence for involvement in repair in vivo of two endonucleases specific for DNA containing pyrimidine dimers.

Involvement of Py pyrimidine dimers Py correnconucleases I and II in repair of ultraviolet radiation damage in vivo by Micrococcus luteus has been demonstrated by their absence in the ultraviolet-sensitive mutant DB-7 derived by treatment of the wild type parent with N-methyl-N'-nitro-N-nitrosoguanidine. The necessity for their combined action in DNA repair in M. luteus is shown by: (a) reactivation of ultraviolet-damaged phiX174 RFI DNA in incision-defective hosts after in vivo treatment with both enzymes, (b) correlation between survival after ultraviolet irradiation and the level of the two enzymes, and (c) increased levels of repair synthesis after ultraviolet irradiation of toluenized cells DB-400 with wild type correndonuclease levels when compared with the transformant DB-200 and the mutant DB-7, which lack one or both enzymes.

DNA Repair↗
PubMed1977

Effects on hypothalamic and telencephalic NE and 5-HT of tegmental knife cuts that produce hyperphagia or hyperdipsia in the rat.

Knife cuts in the coronal plane through various aspects of the midbrain tegmentum produced hyperphagia, hyperdipsia, or no effect on ingestive behavior. All of the cuts significantly depleted NE and 5-HT from hypothalamus and forebrain. The brains of hyperphagic or hyperdipsic animals did not differ from those of normophagic and normodipsic animals with respect to hypothalamic NE or 5-HT or telencephalic NE. Both hyperphagic and hyperdipsic animals had significantly lower concentrations of 5-HT in forebrain than rats which sustained similar cuts in the tegmentum which did not affect ingestive behavior.

Animals↗
PubMed1977

Some biochemical effects of zona incerta lesions that interfere with the regulation of water intake.

The concentration of NE, DA and 5-HT in forebrain, striatum, and hypothalamus was measured after zona incerta (ZI) lesions that have been shown to result in general hypodipsia; adipsia during periods of food deprivation; impaired or abolished drinking in response to osmotic challenges (but not polyethylene glycol); impaired drinking after systemic isoproterenol or central angiotensin; and impaired or abolished feeding in response to 2-deoxy-D-glucose. The lesions produced a significant (40-50%) depletion of forebrain NE but a correlational analysis of the behavioral and biochemical effects of the lesions failed to indicate a causal relationship. The lesions did not reliably affect (a) forebrain DA or 5-HT; (b) striatal DA or 5-HT; (c) hypothalamic DA, NE or 5-HT. The results of these experiments indicate that significant impairments in ingestive behavior can be demonstrated in animals with diencephalic lesions that do not result in striatal (or forebrain) DA depletions. This confirms previous behavioral analyses showing that ZI lesions which interfere with ingestive behavior do not produce the debilitating sensory or motor dysfunctions typical of the rat with lateral hypothalamic lesions.

Animals↗
PubMed1976

Human correxonuclease. Purification and properties of a DNA repair exonuclease from placenta.

An exonuclease, which hydrolyzes single-stranded DNA, has been purified from human placenta. It initiates hydrolysis at both the 3' and 5' termini of such DNA with equal facility, yielding 5'-phosphorylated oligonucleotides averaging 4 nucleotides in length. These oligonucleotides are released from both termini at equal rates with the same size distribution. Although not detectably active against intact native DNA, this enzyme can initiate hydrolysis at single-stranded breaks, creating a gap 30 to 40 nucleotides long. If a pyrimidine dimer is adjacent to this break, the enzyme, by virtue of its action at internal phosphodiester bonds, can excise such dimers. We refer to this exonuclease as human correxonuclease because of its excision capability.

Alkaline Phosphatase↗
PubMed1976

A DNA binding protein from human placenta specific for ultraviolet damaged DNA.

A DNA-binding protein specific for ultraviolet irradiated DNA has been purified extensively from human placenta. The binding preparation is free of exonuclease, polymerase, endonuclease, and N-glycosidase activity. The binding activity is salt dependent and is specific for double-stranded irradiated DNA. DNA from which the pyrimidine dimers have been monomerized by the action of photolyase (photoreactivating enzyme) remains an effective substrate for the binding protein, suggesting that the protein recognizes photoproducts other than pyrimidine dimers. This is supported by the finding that DNA irradiated under conditions which introduce only pyrimidine dimers is not a substrate for the binding protein. Examination of three of the xeroderma pigmentosum complementation groups has revealed no deficiency in this binding activity.

Binding Sites↗
PubMed1975

Granulocyte transfusions in treatment of infections in patients with acute leukaemia and aplastic anaemia.

By use of the continuous-flow blood-cell separator 137 bags of granulocyte-rich plasma were obtained from normal donors (59 bags) and patients with chronic granulocytic leukaemia (C.G.L.) (78 bags). Eighty-nine courses of granulocyte transfusion therapy consisting of 1 or more such bags were administered to forty-one ABO-compatible patients with acute leukaemia or aplastic anaemia, who had definite or probable infections that had failed to respond to antibiotics. The fever resolved after 67% of courses of transfusions of two or more bags but after only 24% of transfusions of single bags of granulocytes (p less than 0-01), and this result suggests that this form of treatment is in general effective. Granulocytes from C.G.L. and normal donors were equally effective, although transfusion reactions were commoner after C.G.L. cells (33% versus 12%, respectively, p less than 0-05). C.G.L. grafts, and probable graft-versus-host disease, occurred in three recipients of unirradiated C.G.L. cells. Recipients of normal cells whose fevers resolved received on average four times as many granulocytes per sq.m. as those fevers did not respond. No such difference was found when C.G.L. cells were used. The fever was more likely to resolve in recipients with established or clinically probable bacterial or fungal infections than in those with fever of uncertain cause. Fever was less likely to resolve in recipients with peripheral blood granulocyte counts before transfusion of greater than 1000 per mul. It is concluded that granulocyte transfusion therapy is a valuable advance in the management of infections in neutropenic patients.

Adolescent↗
PubMed1975

The Escherichia coli UV endonuclease (correndonuclease II).

An endonuclease from Escherichia coli which acts specificially upon UV-irradiated DNA (correndonuclease II) and is absent from the uvrA and uvrB mutants has been isolated and partially chacterized. The enzyme is present in normal amounts in the urvC mutant. It elutes from phosphocellulose at about 0.25 M potassium phosphate (pH 7.5) and passes through dialysis tubing. The enzyme binds tightly to UV-irradiated DNA but does not bind to unirradiated DNA. The enzyme incises irradiated DNA to the 5' side of a pyrimidine dimer and leaves a 5'-phosphoryl terminus which can be resealed with polynucleotide ligase. The Km of the enzyme is about 1.5 X 10(-8) M dimers. Endonucleolytic activity of the enzyme is inhibited by caffeine with a KI of about 10mM.

Caffeine↗
PubMed1975

Enzymatic repair of UV-irradiated DNA in vitro.

Excision repair of UV-damaged Bacillus subtilis transforming DNA has been carried out by a sequential enzyme system in vitro. Incision adjacent to the pyrimidine dimer in the DNA strand by correndonuclease II-initiated excision of the damage by the 5' in equilibrium 3'-directed exonuclease of the Micrococcus luteus DNA polymerase. Reinsertion of nucleotides into the gap in the strand by the DNA polymerase at 10 degrees C terminated in a single-strand break which was sealed by a polynucleotide ligase, thereby repairing the DNA strand. This restored biological activity to damaged DNA up to doses resulting in 60% inactivation of transforming activity. At higher doses, less repair was achieved, due to the development of double-strand breaks during the in vitro incision and excision steps.

Bacillus subtilis↗
PubMed1975

Functional organization of the rat amygdala with respect to avoidance behavior.

Bilateral electrolytic lesions in the periamygdaloid piriform cortex of female albino rats produced marked disruptive effects on the acquisition of active avoidance responses in a 1-way as well as a 2-way test situation, significantly impaired passive avoidance behavior, and inhibited feeding in a novel environment. Lesions in each of the 6 major subdivisions of the amygdala (cortical, medial, central, intercalated, lateral, and basolateral nuclei) consistently produced facilitatory effects on active avoidance behavior in 1-way as 2-way situations. Passive avoidance behavior was impaired in animals with lesions in the central, intercalated, and basolateral nuclei. Damage to the anterior amygdaloid area or the the nuclei of the lateral olfactory tract did not reliably affect active or passive avoidance behavior.

Agonistic Behavior↗
PubMed1975

Some behavioral effects of transecting ventral or dorsal fiber connections of the septum in the rat.

The behavioral effects of large electrolytic lesions in the septal area were compared with those of knife cuts that severed the ventral or dorsal connections of this structure. Rats with septal lesions lost weight and were transiently hyperdipsic. Ventral cuts produced similar effects, but dorsal cuts did not. All three operations decreased the latency to eat in a novel environment, increased the intake of sweetened milk, enhanced acquisition of a food-rewarded running response, and facilitated acquisition of a shuttle box avoidance response, The lesion, but neither of the knife cuts, reduced the effects of punishment and impaired the acquisition of a one-way avoidance response.

Animals↗
PubMed1974

An endonuclease from Escherichia coli that acts preferentially on UV-irradiated DNA and is absent from the uvrA and uvrB mutants.

At least two endonucleolytic activities that preferentially incise ultraviolet (UV)-irradiated DNA exist in extracts of E. coli. These two activities can be separated by phosphocellulose chromatographic fractionation. The subject of this paper is one of these activities, which elutes from phosphocellulose with 0.25 M potassium phosphate, pH 7.5. This endonucleolytic activity specific for UV-irradiated DNA is absent from partially purified extracts of uvrA and uvrB mutants, which are defective in excision of pyrimidine dimers, but is present in normal amounts in the uvrC excision-defective mutant. The enzyme binds very tightly and specifically to UV-irradiated DNA. Binding can be prevented by prior treatment of the irradiated DNA with photoreactivating enzyme. This binding activity is absent in uvrA and uvrB mutants, but present in uvrC and uvrD mutants.

Catalysis↗