Ibrahim A. Aksoy

Sulfation and sulfotransferases 1: Sulfotransferase molecular biology: cDNAs and genes.

Sulfotransferase (ST) enzymes cata‐lyze the sulfate conjugation of many hormones, neu‐rotransmitters, drugs, and xenobiotic compounds. These reactions result in enhanced renal excretion of the sulfate‐conjugated reaction products, but they can also lead to the formation of “bioactivated” metabolites. ST enzymes are members of an emerging gene superfamily that presently includes phenol ST (PST), hydroxysteroid ST (HSST), and, in plants, flavonol ST (FST) “families,” members of which share at least 45% amino acid sequence iden‐tity. These families can be further subdivided into “subfamilies” that are at least 60% identical in amino acid sequence. For example, the PST family includes both PST and estrogen ST (EST) subfamilies. Amino acid sequence motifs exist within ST enzymes that are conserved throughout phylogeny. These signature sequences may be involved in the binding of 3 ‘‐phosphoadenosine‐5 ‘‐phosphosulfate, the cosubstrate for the sulfonation reaction. There are presently five known human cytosolic ST en‐zymes: an EST, an HSST, and three PSTs. cDNAs and genes for all of these enzymes have been cloned, and chromosomal localizations have been reported for all five genes. Genes for these human enzymes, as well as those of other mammalian cytosolic ST enzymes that have been cloned, show a high degree of structural homology, with conservation of the lo‐cations of most intron/exon splice junctions. Human ST enzyme expression varies among individuals. Functionally significant genetic polymorphisms for ST enzymes in humans have been reported, and other molecular genetic mechanisms that might be involved in the regulation of the expression of these enzymes are being explored. Knowledge of the mo‐lecular biology of cytosolic ST enzymes, when placed within a context provided by decades of biochemical research, promises to significantly enhance our understanding of the regulation of the sulfate conjugation of hormones, neurotransmitters, and drugs.—Weinshilboum, R. M., Otterness, D. M., Aksoy, I. A., Wood, T. C., Her, C., Rafto‐ gianis, R. B. Sulfotransferase molecular biology: cDNAs and genes. FASEB J. 11, 3‐14 (1997)

Human liver dehydroepiandrosterone sulfotransferase: Nature and extent of individual variation

Dehydroepiandrosterone sulfotransferase (DHEA ST) catalyzes the sulfation of steroid hormones such as DHEA, estrone, and estradiol. As a first step in pharmacogenetic studies of DHEA ST in humans, we measured individual variation in DHEA ST enzymatic activity and thermal stability in 94 samples of human hepatic tissue, 39 of which were from patients with normal liver function studies. Neither level of enzyme activity nor thermal stability were significantly correlated with either time of tissue storage at −80° C or patient age. In addition, there were no gender‐dependent differences in DHEA ST activity in these samples. DHEA ST enzymatic activity varied 4.6‐fold, with a mean value of 317 ± 100 units/gm tissue (mean ± SD) in all samples and 318 ± 104 units/gm in the subset of 39 samples from patients with normal hepatic function studies. Frequency distributions of DHEA ST activity for both the entire group of 94 samples and the subset of 39 were bimodal, with 25% and 21% included in a high activity subgroup, respectively. The presence of this high activity subgroup was confirmed when data for samples from male and female patients were evaluated separately and when only data for white patients were examined. The existence of a subgroup of subjects with a high level of DHEA ST enzymatic activity in liver and a 4.6‐fold range in this activity have implications for individual differences in the sulfate conjugation of endogenous and exogenously administered steroid hormones and raise the possibility of pharmacogenetic regulation of this important enzyme in humans.

D-3-Deoxy-3-substituted myo-inositol analogues as inhibitors of cell growth

SummaryA number of unnaturald-3-deoxy-3-substitutedmyo-inositols were synthesized and their effects on the growth of wild-type NIH 3T3 cells and oncogenetransformed NIH 3T3 cells were studied. The compounds were found to exhibit a diversity of growth-inhibitory activities and showed selectivity in inhibiting the growth of some transformed cells as compared with wild-type cells. Remarkably,d-3-deoxy-3-azido-myo-inositol exhibited potent growth-inhibitory effects toward v-sis-transformed NIH 3T3 cells but had little effect on the growth of wildtype cells. The growth-inhibitory effects of themyo-inositol analogues were antagonized bymyo-inositol. Since [3H]-3-deoxy-3-fluoro-myo-inositol was shown to be taken up by cells and incorporated into cellular phospholipids, we suggest that these unnaturalmyo-inositol analogues may act as antimetabolites in the phosphatidylinositol intracellular signalling pathways. Because cells transformed by oncogenes often exhibit elevated phosphatidylinositol turnover, the inhibition of signalling pathways that mediate oncogene action could offer new opportunities for controlling the growth of cancer cells.

Spinal Accessory Neuropathy Associated With Deep Tissue Massage: A Case Report

Spinal accessory neuropathy (SAN) causes impaired arm mobility and pain. The spinal accessory nerve is often injured during surgical procedures such as neck dissection for tumor resection or cervical lymph node biopsy. Other traumatic injuries may also occur. SAN causes weakness of the trapezius muscle and, less frequently, of the sternocleidomastoid muscle. The clinical consequence of trapezius muscle weakness includes impaired stability of the scapula leading to upper limb dysfunction and pain. We present a rare and illustrative case of SAN associated with deep tissue massage leading to scapular winging and droopy shoulder as a result of weakness of the trapezius muscle.

Synthesis of D-3-deoxy-myo-inositol 1,4,5-trisphosphate and its effect on Ca2+ release in NIH 3T3 cells

The synthesis of D-3-deoxy-myo-inositol 1,4,5-trisphosphate is reported together with its effect on Ca2+ release in permeabilized NIH 3T3 cells.

Poster 67: Lumbar intraspinal synovial cyst: a case report1

Abstract Setting: Tertiary medical center physical medicine and rehabilitation unit. Patient: A 67-year-old woman with intractable right lower-extremity pain and paresthesias. Case Description: The patient presented with a 2 month-history of acute onset right buttock pain with radiation into calf and foot. She also had numbness and tingling in her right foot. There was no trauma or unusual activity, however, she had subtle right leg discomfort for many years prior to onset of pain. The patient had no subjective weakness or difficulty in bowel or bladder control. Neurologic examination revealed absent right ankle jerk and reduced sensation in S1 distribution. Motor strength was normal. Lumbar spine magnetic resonance imaging (MRI) revealed a juxta-facet intraspinal synovial cyst at the right L5-S1 level. This caused deformity and compression of the right S1 nerve root. There were also smaller extraspinal synovial cysts at L5-S1 level posteriorly. Assessment/Results: The patient underwent right L5 partial, inferior hemilaminectomy, L5-S1 medial facetectomy, foraminotomy of the S1 nerve root, and gross total resection of the L5-S1 level synovial cyst. Postoperatively, she reported relief of right lower-extremity pain for several hours. She then developed recurrence of right leg pain without weakness. MRI revealed hematoma formation at the operative bed. The hematoma was evacuated promptly, resulting in complete resolution of symptoms. Discussion: This case represents a classic presentation of a large intraspinal synovial cyst causing radiculopathy and outcome of surgical excision with the infrequent postoperative complication of hematoma. Conclusion: Intraspinal synovial cysts can cause intractable radicular pain. MRI studies are warranted for intractable radiculopathies.