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Biomedical subjects

D Holtzman

Publications and source records attributed to D Holtzman.

106 records · Page 6Linked to original sources
PubMed1976

Early effects of inorganic lead on immature rat brain mitochondrial respiration.

Inorganic lead, added to the diet of suckling rat in high doses, produces an encephalopathy similar to that seen in the immature human. Pathologic changes of edema and hemorrhage are seen earliest and are most prominent in the cerebellum. In this study, we measured respiration in cerebral hemisphere and cerebellar mitochondria isolated from led-fed and age-matched normal rat pups. Lactating mothers were begun on ad libitum feedins containing 4% lead carbonate when their pups were 2 weeks old. Mitochondria were isolated by differential centrifugation. Oxygen consumption was measured polarographically, NAD-linked respiration was measured with oxidation of the substrate pair, glutamate and malate. Cytochrome oxidase (cytochrome c oxidase, EC. 1.9.3.1) activity was measured in the presence of tetramethyl-p-phenylenediamine dihydrochloride (TMPD) and ascorbate. Within 2 days of starting lead feedings, rat pups showed a significant loss in body weight (P less than 0.02) and, after 1 week, a significant loss in cerebral hemisphere wet weight (P less than 0.01) compared with controls. Overt encephalopathy appeared in pups from two of nine litters receiving lead feedings for 1 week and in half of the litters after 2 weeks of feedings. None of the lead-fed mothers developed encephalopathic signs. With oxidation of the NAD-linked substrate pair, there was a progressive decrease, relative to controls, in ADP/O ratios in both cerebellar and cerebral mitochondria from lead-fed animals. After 2 weeks these differences were significant in mitochondria from both regions (cerebellum, P less than 0.02; cerebrum, P less than 0.005). Respiratory control ratios were significantly lower in cerebellar mitochondria from lead-fed rats within 2 days of beginning feedings (P less than 0.02) and in mitochondria from both regions after 2 weeks of lead feedings (cerebellum, P less than 0.01; cerebrum, P less than 0.05). The decrease in control ratios in cerebellar mitochondria from animals receivint lead feedings for 1 week or less was due to a small decrease in state 3 respiration and a large, but inconsistent, increase in state 4 respiration. The decrease in control ratios in both cerebellar and cerebral hemisphere mitochondria after 2 weeks of lead feedings was due to a marked inhibition of state 3 respiration, relative to controls (cerebellum, P less than 0.01; cerebral hemisphers, P less than 0.05). In cerebellar mitochondria from lead-fed animals, cytochrome oxidase activity showed similar changes compared with controls: a highly significant (P less than 0.001) increase within 2 days of beginning feedings and a significant (P less than 0.01) decrease after 2 weeks of feedings.

Adenosine Diphosphate↗
PubMed1969

1-delta9-tetrahydrocannabinol: neurochemical and behavioral effects in the mouse.

Administration of pure 1-delta(9)-tetrahydrocannabinol to mice had the following dose-dependent nzeurochemical and behavioral effects: a slight but significant increase in concentrations of 5-hydroxytryptamine in whole brain; a decrease in concentration of norepinephrine in brain after administration of low doses and an increase after high doses; diminished spontaneous activity, mloderate hypothermnia, hypersetisitivity to tactile and auditory stimiuli, and ataxia after low doses; and sedation, pronounced hypothermia, and markedly diminished spon taneous activity and reactivity after high doses. The duration of the effects on body temperature and spontaneous activity correlated generally with the changes in brain amines. The characteristic changes in brain amines do not correspond exactly to those observed with other psychotropic drugs.

Animals↗
PubMed1967

The effect of low ionic strength extracellular solutions on the resting potential in skeletal muscle fibers.

Intracellular measurements of the resting potential were made in fibers of the frog sartorius muscle in solutions of varying salt composition and concentration to determine the effects of low ionic strength extracellular solutions on the resting potential. Changes in the glass microelectrode tip potential in low ionic strength solutions were minimized by adding ThCl(4) to the extracellular solution. These experimental conditions allowed measurement of the relationship of the resting potential to the concentration of the salt in the extracellular solution by replacing it with the nonionic substance, sucrose. Substitution of sucrose for the extracellular NaCl produced a stable depolarization which was logarithmically related to the NaCl concentration. Substitution of sucrose for choline Cl, instead of NaCl, produced the same degree of depolarization. When Na salts of anions less permeable than chloride (Br, I, NO(3)) were used, the resting potentials in 116 mM solutions were close to those with chloride (+/-3mv). The depolarizations produced in low ionic strength solutions of these salts were significantly less than those with chloride.

Animals↗
PubMedDate not supplied

Multi-echo 31P spectroscopic imaging of ATP: a scan time reduction strategy.

Spectroscopic imaging of 31P metabolites and adenosine triphosphate (ATP) in particular with multiple spin echoes may prove useful for reducing data acquisition times. The usual T2 decay processes that degrade multi-echo spectroscopic imaging methods, however, are further compounded by J-coupling modulations in the case of ATP. We determine how these modulations affect multi-echo spectroscopic imaging k-space data and produce systematic spatial misregistrations of the ATP resonances. The specific J-coupling modulations of ATP are determined to identify echo-spacing effects in multi-echo spectroscopic imaging of ATP and to determine appropriate post-processing correction schemes to address the spatial misregistration problem. An in vivo demonstration of the technique that offers a threefold reduction in scan time compared to conventional SI methods is provided and compared with the conventional SI approach.

Adenosine Triphosphate↗
PubMedDate not supplied

RARE imaging of PCr in human forearm muscles.

Rapid acquisition with relaxation enhancement (RARE) sequences have been used to map the 31P phosphocreatine (PCr) signal in human forearms at 4.7 T. Signal-to-noise levels of approximately 10 were achieved from the major muscle groups in 5.5-minute scan times with a spatial resolution of 4 x 2 x 2 cm3. Exercise caused demonstrable reductions in PCr signal from activated muscles, which correlated with affected muscle groups in T2-weighted proton images. RARE imaging of the PCr signal at 4.7 T is feasible and, with technically achievable improvements in signal-to-noise ratio, should prove useful in studying energy metabolism in muscle and other organs.

Forearm↗
PubMedDate not supplied

Hyperthermia-induced seizures in rat pups with preexisting ischemic brain injury.

To investigate the mechanism(s) relating perinatal brain injury to increased seizure sensitivity in the developmental age period, we studied hyperthermia-induced seizures in rat pups with a preexisting unilateral ischemic cerebral injury. At 2 days of age, the pups underwent a carotid artery ligation followed by 20 min of anoxia. By light microscopy, there were no pathologic changes in the postischemic cerebral cortex at 5, 10, or 20 days of age. Seizures were induced by hyperthermia at 5, 10, 15, or 20 days of age. Seizure temperature thresholds increased with maturation in both postischemic and control animals. Temperature thresholds for behavioral seizures were significantly lower at 10, 15, and 20 days in postischemic pups, compared with control animals. By EEG criteria, seizure thresholds also were lower at 10 and 15 days in the postischemic pups compared with control animals. Preictal EEG slowing appeared at the same temperature in experimental and control animals at all ages. We conclude that the rat pup is an appropriate model for the study of enhanced epileptogenesis in the presence of a perinatal ischemic encephalopathy.

Animals↗
PubMedDate not supplied

Brain creatine kinase and creatine transporter proteins in normal and creatine-treated rabbit pups.

Systemic creatine (Cr) supplementation increases brain phosphocreatine (PCr) and prevents hypoxic seizures in 15-day-old rabbits. Between 5 and 30 days of age during normal development, rabbit gray matter mitochondrial creatine kinase (Mi-CK) increases 400% while cytosolic CK (BB-CK) increases 60%. In white matter, both isoenzymes show smaller, similar increases (40%) during this period. The Cr transporter protein decreases 60% between 5 and 15 days in both regions. In vivo CK rate constants measured by (31)P nuclear magnetic resonance increase 30% between 10 and 20 days, and then fall 50% between 20 and 30 days in predominantly gray matter slices. Similar maturational changes are seen in predominantly white matter slices. Injecting Cr at 15 days does not significantly change BB-CK or Mi-CK isoenzymes or the in vivo CK reaction rate constants. Thus, the largest change in the CK system associated with suppression of hypoxic seizures in Cr-treated rabbits is increased PCr in gray and white matter.

Aging↗
PubMedDate not supplied

HIV/AIDS knowledge and sexual behavior among high school students.

Data from the 1989 Secondary School Student Health Risk Survey indicate that 54 percent of all high school students in the United States had had some form of HIV/AIDS education in school. Responses to a questionnaire on HIV/AIDS knowledge show that nearly all students knew the two main modes of HIV transmission--intravenous drug use and sexual intercourse. Students who had been taught about HIV and AIDS in school gave correct answers to questions about the virus more often than those who had not received instruction. Students who knew more about HIV transmission were less likely to report having had two or more sexual partners and more likely to report consistent condom use.

Acquired Immunodeficiency Syndrome↗
PubMedDate not supplied

Parent and peer communication effects on AIDS-related behavior among U.S. high school students.

Data from a 1989 national probability sample of 8,098 high school students in the United States indicate that young people's discussions about the human immunodeficiency virus (HIV) with parents and with peers are highly correlated and have opposite effects on behavior. Students who discussed HIV with their parents were less likely than those who did not to have had multiple sex partners, to have had unprotected sexual intercourse and to have ever injected drugs; on the other hand, students who discussed HIV with their peers were more likely than those who did not to have had multiple partners and to have had unprotected sexual intercourse. Subgroup analyses show that young women were influenced more by HIV discussions with parents, while young men were influenced more by discussions with peers; some communication effects differed by race and ethnicity. Students who received HIV instruction in school were more likely to have talked about HIV with both parents and peers.

Adolescent↗