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T J Hoffman

Publications and source records attributed to T J Hoffman.

At least 19 recordsLinked to original sources
PubMed1998

Design and characterization of alpha-melanotropin peptide analogs cyclized through rhenium and technetium metal coordination.

alpha-Melanocyte stimulating hormone (alpha-MSH) analogs, cyclized through site-specific rhenium (Re) and technetium (Tc) metal coordination, were structurally characterized and analyzed for their abilities to bind alpha-MSH receptors present on melanoma cells and in tumor-bearing mice. Results from receptor-binding assays conducted with B16 F1 murine melanoma cells indicated that receptor-binding affinity was reduced to approximately 1% of its original levels after Re incorporation into the cyclic Cys4,10, D-Phe7-alpha-MSH4-13 analog. Structural analysis of the Re-peptide complex showed that the disulfide bond of the original peptide was replaced by thiolate-metal-thiolate cyclization. A comparison of the metal-bound and metal-free structures indicated that metal complexation dramatically altered the structure of the receptor-binding core sequence. Redesign of the metal binding site resulted in a second-generation Re-peptide complex (ReCCMSH) that displayed a receptor-binding affinity of 2.9 nM, 25-fold higher than the initial Re-alpha-MSH analog. Characterization of the second-generation Re-peptide complex indicated that the peptide was still cyclized through Re coordination, but the structure of the receptor-binding sequence was no longer constrained. The corresponding 99mTc- and 188ReCCMSH complexes were synthesized and shown to be stable in phosphate-buffered saline and to challenges from diethylenetriaminepentaacetic acid (DTPA) and free cysteine. In vivo, the 99mTcCCMSH complex exhibited significant tumor uptake and retention and was effective in imaging melanoma in a murine-tumor model system. Cyclization of alpha-MSH analogs via 99mTc and 188Re yields chemically stable and biologically active molecules with potential melanoma-imaging and therapeutic properties.

Amino Acid Sequence↗
PubMed1997

Child sexual revictimization by multiple perpetrators.

OBJECTIVE: The objectives of this study were to describe feelings, disclosure characteristics, family dysfunction, and health risky behaviors in those adolescents having unwanted sexual experiences (USE; any kind of sexual touching that was bad, uncomfortable, or forced) with multiple perpetrators and to compare these parameters with those adolescents having USE(s) with single perpetrators. METHOD: A cross-sectional survey of consecutive waiting room patients from four clinic sites was done in 538 adolescents and young adults; 76% of the study population were Hispanic and over half were poor. One hundred sixty-one subjects with single perpetrator USE(s) were compared with 97 subjects who had USE(s) with more than one perpetrator. RESULTS: Victims of multiple perpetrators were more likely than victims of single perpetrators to react with self-blame and delay disclosure of USE due to shame. When compared with victims of single perpetrators, those with multiple perpetrators were more likely to disclose their USE to protect self or others or because they became weary or intolerant of the abuse. Although family violence and substance abuse were common in both victims of single and multiple perpetrators of USE, these factors appeared to potentiate the likelihood of repeated victimization in childhood. Prevalence of health risky behaviors did not differ between the two groups. CONCLUSIONS: The findings indicated that sexual revictimization by multiple perpetrators is not uncommon and suggest that abused children should be questioned about this possibility. Children and teenagers who have USE(s) with more than one perpetrator may have more difficulties with psychological recovery due to increased shame and self-blame.

Adolescent↗
PubMed1995

Unwanted and illegal sexual experiences in childhood and adolescence.

Three hundred forty-two anonymous surveys regarding unwanted sexual experiences (USE) were filled out in three clinic sites: a pediatric sexual abuse clinic, family practice clinic, and family planning clinic. In the latter two clinics, 40% of females and 16% of males had at least one unwanted sexual experience prior to turning 18 years old. Only 91% of the sexual abuse clinic patients indicated their experience was unwanted. In addition, 27% of the subjects had wanted sexual experiences that were illegal and underreported: These experiences involved a partner at least 4 years older or younger. While feelings of victimization were most common, self-blame and naivete about the abuse were also frequently reported, especially in those who had an USE with a peer. Ambivalence, self-blame, and peer pressure were associated with a lower tendency to disclose one's USE. Although unwanted and illegal sexual experiences were less common in Hispanic females, feelings of self-blame and ambivalence regarding their USE were more frequent in comparison with White females. These findings have important investigative and therapeutic implications for professionals who encounter victims of sexual abuse.

Adolescent↗
PubMed1993

Decrease in locus coeruleus [3H]idazoxan binding site density in genetically epilepsy-prone (GEPR) rats.

Deficits in norepinephrine synthesis, transmitter level, turnover and reuptake have been reported in the brain of genetically epilepsy-prone (GEPR) rats. We investigated the hypothesis that these alterations may trigger a compensatory downregulation of locus coeruleus alpha 2-adrenergic receptors and an upregulation of postsynaptic alpha 2-adrenergic receptor density in forebrain regions of GEPR rat brain. alpha 2-adrenergic receptor density was measured in the locus coeruleus and 7 forebrain regions of control and GEPR rats by in vitro [3H]idazoxan autoradiography. Specific [3H]idazoxan binding site density was decreased significantly in the locus coeruleus of both GEPR-3 and GEPR-9 rats compared to controls. No significant differences in specific [3H]idazoxan binding were observed in the 7 forebrain regions of GEPR-9 rats compared to control. Reduced locus coeruleus alpha 2-adrenergic receptor density in GEPR rats may produce a net increase in locus coeruleus noradrenergic cell firing, an effect which could, in part, offset the impact of reduced noradrenergic influence in GEPR rat forebrain. Additionally, decreased norepinephrine levels in GEPR rat brain may be a long-term consequence of reduced alpha 2-adrenergic receptor-mediated inhibition of locus coeruleus firing activity.

Adrenergic alpha-Antagonists↗
PubMed1992

The effect of ligand structure on glutathione-mediated decomposition of propylene amine oxime derivatives.

Tetramethylpropyleneamine oxime (TMPAO) was synthesized and complexed to 99mTc. 99mTc-TMPAO samples, when challenged with reduced glutathione (GSH), were shown to have two GSH sensitive components, similar to a mixture of d,l and meso 99mTc-HMPAO. One component had a GSH-induced second-order dissociation rate constant (K2) similar to 99mTc-meso-HMPAO. Despite the presence of a large fraction of this component in these samples, brain uptake and autoradiographic studies with 99mTc-TMPAO were equivalent to 99mTc-d,l-HMPAO suggesting that both the d,l and meso 99mTc-TMPAO isomers are efficiently trapped in brain.

Animals↗
PubMed1992

Radiographic and neuro-SPECT imaging in an immature third ventricle teratoma: case report.

We report a case of an immature teratoma of the third ventricle, which was preoperatively thought to be a choroid plexus papilloma. The diagnosis was made by biopsy since the radiographic (CT, MRI), angiographic and scintigraphic findings ([99mTc]pertechnetate, 99mTc-DTPA, 99mTc-HMPAO brain SPECT) were nonspecific. Disruption of the blood-brain barrier is the mechanism for radionuclidic and contrast tumoral uptake and is demonstrated by marked contrast enhancement on CT and focal concentration on [99mTc]pertechnetate and 99mTc-DTPA images. No suppression of [99mTc]pertechnetate tumor uptake was observed following the administration of potassium perchlorate. Increased concentration of tumor protein is suggested by the increased signal on the T1-weighted magnetic resonance images and high [99mTc]pertechnetate uptake. The tumor's detection on the 99mTc-HMPAO brain SPECT was due to its intraventricular location. A number of potential mechanisms for brain tumor localization of 99mTc-HMPAO are discussed.

Cerebral Ventricle Neoplasms↗
PubMed1988

Retention of [99mTc]-d,l-HM-PAO in rat brain: an autoradiographic study.

The regional cerebral distribution pattern of [99mTc]-d,l-HM-PAO in rat brain was studied by autoradiography. The regional cerebral uptake of this tracer is related to regional cerebral blood flow (rCBF); however, the ratio of retained radioactivity (determined by digital imaging techniques) in gray matter compared to white matter is lower than that reported for the blood flow ratio. Considerable inhomogeneity is observed in cortical gray matter for at least 60 min postinjection, demonstrating that minimal, if any, cerebral redistribution of this agent occurs.

Animals↗
PubMed1988

Microcomputer-based digital image analysis system for quantitative autoradiography.

A computerized image processing system utilizing an IBM-XT personal microcomputer with the capability of performing quantitative cerebral autoradiography is described. All of the system components are standard computer and optical hardware that can be easily assembled. The system has 512 horizontal by 512 vertical axis resolution with 8 bits per pixel (256 gray levels). Unlike other dedicated image processing systems, the IBM-XT permits the assembly of an efficient, low-cost image analysis system without sacrificing other capabilities of the IBM personal computer. The application of this system in both qualitative and quantitative autoradiography has been the principal factor in developing a new radiopharmaceutical to measure regional cerebral blood flow.

Animals↗
PubMed1987

Two populations of tyrosine hydroxylase-positive cells occur in the spinal cord of the chick embryo and hatchling.

The existence of tyrosine hydroxylase (TH)-containing neurons in the spinal cord of the chick embryo was investigated by anti-TH immunocytochemistry. Two populations of intensely immunostained cells were observed along the entire extent of the cord, beginning late in chick embryogenesis. One group of TH-positive cells was particularly numerous and found ventral to the central canal. The other group, which was smaller in number, was located along the superficial and lateral border of the dorsal horn of the spinal cord. When examined by the glyoxylic acid histofluorescence technique, cells could be visualized only very infrequently ventral to the central canal, and not at all within the dorsal horn. However, after pretreatment of hatchlings with the catecholamine synthesis precursor L-DOPA, cells ventral to the canal were readily observed by histofluorescence, while the dorsally located cells seldom visualized. Since these populations of TH-positive cells appear to only partially express the catecholaminergic phenotype, these cells may provide a model in which factors regulating the expression of neurotransmitter phenotypes can be examined in neurons of the developing CNS.

Animals↗
PubMed1986

Analysis of the change in number of serotonergic neurons in the chick spinal cord during embryonic development.

The existence of serotonin (5-HT)-containing neurons in the spinal cord of the chick embryo was examined by anti-5-HT immunocytochemistry. The first immunoreactive cells were observed in embryos at 7 days of incubation (E7) and were initially located within the floor plate of the early spinal cord. By E9, immunostained cells occurred throughout the length of the spinal cord and were frequently encountered in most transverse sections of the cord. When examined at later embryonic ages of E12, 17 and at hatching (E21 or 22), the 5-HT cells became progressively more difficult to find with the advancing age of the embryos. To determine if this population of spinal cord 5-HT neurons actually diminished during development, a detailed quantitative analysis was undertaken to estimate the number of 5-HT cells in the cord of chick embryos at different ages. The results of this investigation demonstrated that the size of the 5-HT neuronal population rose rapidly from E7 and plateaued (at approximately 3500 neurons) between E9 and E12. As anticipated, the number of 5-HT cells at E17 decreased at all cord levels. Surprisingly, however, the number of spinal cord 5-HT neurons at hatching increased (depending on the cord level) either back to, or above, the counts estimated for the earlier ages of E9 and E12. Therefore, cells expressing the 5-HT phenotype in the spinal cord of the chick embryo persist throughout the period of embryonic development, rather than appear transiently.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Cerebral uptake and retention of 99Tcm-hexamethylpropyleneamine oxime (99Tcm-HM-PAO).

A new radiopharmaceutical, 99Tcm-hexamethylpropyleneamine oxime (99Tcm-HM-PAO) is described. This agent displays considerable promise for imaging cerebral blood flow. In studies in rats and one human volunteer, 99Tcm-HM-PAO demonstrates good brain uptake, prolonged retention of activity in the brain, and slow regional redistribution. These properties suggest that this new radiopharmaceutical is ideal for single photon emission tomographic (SPECT) imaging of cerebral blood flow.

Animals↗
PubMed1984

99mTc-propylene amine oxime (99mTc-PnAO); a potential brain radiopharmaceutical.

Propylene amine oxime (PnAO) forms a neutral lipid soluble complex with 99mTc. 99mTc-PnAO can be prepared by simple reduction of 99mTc-pertechnetate with stannous ion in the presence of excess PnAO in saline at or near neutral pH. This agent will passively penetrate biological membranes including the intact blood-brain barrier (BBB) as evidenced by the high brain uptake observed shortly after IV injection. The first-pass extraction efficiency in baboons was estimated to be 80% at normal blood flow. This agent or a derivatized form of 99mTc-PnAO may be useful in assessment of regional cerebral blood flow (rCBF) in humans.

Animals↗
PubMed1984

A neutral lipophilic complex of 99mTc with a multidentate amine oxime.

Propylene amine oxime, 3,3'-(1,3-propanediyldiimino)bis(3-methyl-2-butanone)dioxime, (PnAO) forms a neutral lipophilic complex with 99mTc in greater than 95% yield at room temperature at pH 5-10. The complex can be prepared with generator produced 99mTc using 10(-5) M SnC4H4O6 as the reducing agent at ligand concentrations as low as 3 X 10(-5) M. It is stable in saline solutions for as long as 24 h. [99mTc]PnAO may be useful as an imaging agent which passively diffuses across the blood brain barrier.

Brain↗
PubMed1984

The behavior of neutral amine oxime chelates labelled with Tc at tracer level.

Neutral 99mTc-chelates were formed with propylene amine oxime, 3,3'-(1,3-propanediyldiimino)bis-(3-methyl-2-butanone)-dioxime and other PnAO analogues. Even though the other amine oxime ligands form neutral chelates with 99mTc, the stability, lipophilic and the brain uptake characteristics are less desirable than [99mTc]-PnAO. These results demonstrate that slight modifications in the amine oxime ligand backbone produces significant effects on the chemical and biological behavior of the [99mTc]dioxime chelates.

Animals↗
PubMed1984

Biodistribution of lipophilic 99mTc complexes of cyclam derivatives.

Several n-alkyl-cyclam derivatives were synthesized which form stable single component cationic chelates with 99mTc. These results suggest that the cyclam moiety in these derivatives complexes 99mTc in the same manner as the underivatized macrocycle. Biodistribution studies in mice show that all of these chelates are cleared from circulation by both the kidneys and liver. The ratio and rates of clearance by these organ systems is related to lipid solubility. None of the lypophilic-cationic-99mTc agents show any significant myocardial uptake. Also, these chelates show no significant ability to penetrate the blood-brain-barrier.

Animals↗