Normal CD5+ B lymphocytes are poor stimulators in the autologous mixed lymphocyte reaction (AMLR)

The extracellular calcium-binding (EC) module of human testican (115 residues) was obtained in native form by recombinant production in mammalian cell culture and thus shown to represent an independently folding domain. This module showed a large loss in alpha-helix upon calcium depletion. Apparently only one of the two EF hands binds calcium, with a moderate affinity (Kd =68 microM) about 100-fold lower than in the homologous BM-40 protein. No clear evidence was obtained for collagen binding, indicating that EC modules found in different proteins may not share similar functions.     

Osteotropic agents regulate the expression of osteoclast differentiation factor and osteoprotegerin in osteoblastic stromal cells

The osteoclastogenic factor of osteoblastic origin has recently been elucidated as a novel Tumor Necrosis Factor (TNF)-ligand family member, termed osteoclast differentiation factor (ODF). Using a semiquantitative RT-PCR approach, we sought to determine the mRNA expression of ODF and its decoy receptor, osteoprotegerin (OPG), in a selection of osteoblastic cell lines and in response to three factors representative of different signal transduction pathways, vitamin D receptor, protein kinase A or gp130. Each osteotropic agent, either 1,25-(OH)2D3, PTH or IL-11, promoted an increase in the ratio of ODF:OPG, with maximal stimulation occurring at 24 h, 4 h, and 8 h, respectively, and furthermore each was shown to act in a dose-dependent manner. This report establishes that osteoblastic cell lines incapable of supporting osteoclast formation have markedly reduced ODF expression and also illustrates the importance of the relative abundance of ODF compared with the levels of OPG for the induction of osteoclastogenesis.     

Genital ulcers. Evaluation and treatment

Ulcerations may appear on the genitalia in a variety of both infectious and noninfectious conditions. The vast diversity of etiologies, coupled with the often overlapping morphological features, make the diagnosis of genital ulcerations a challenging endeavor. This article highlights the most important clinical manifestations and laboratory findings which aid in the proper diagnosis of genital ulcerations.     

Thyrotropin-secreting pituitary adenoma

Thyrotropin (TSH)-secreting pituitary adenoma (TSPA) is a rare cause of hyperthyroidism and detailed reports of this entity in Taiwan are uncommon. We report a patient with TSPA with symptoms of hyperthyroidism and describe the presentation, endocrine and histologic findings, and treatment. The patient, a 42-year-old man, presented with a 2-year history of weight loss, palpitation, anxiety, and bad temper. He had increased basal serum thyroxine (T4, 18.3 micrograms/dL) and triiodothyronine (T3, 250 ng/dL) concentrations. The TSH concentration was normal (4.6 microIU/mL) and showed impaired response to stimulation by TSH-releasing hormone. Tests for antithyroid antibodies were negative. Thyroid scintigraphy showed mild thyroid enlargement. The thyroid uptake of radioactive iodine (131I) was high at 2 hours (34%) and 24 hours (63%) after 131I administration. Other serum hormone concentrations were within normal limits. Magnetic resonance imaging of the brain showed a microadenoma in the pituitary region. Octreotide and bromocriptine tests showed 78.4% and 58.3% inhibition of TSH, respectively. The patient underwent trans-sphenoidal pituitary tumor excision, and the symptoms of hyperthyroidism subsided after surgery. Six months after the operation, there was no evidence of recurrence of the tumor or symptoms of hyperthyroidism. Hormonal supplements were also not necessary. In conclusion, TSPA is a rare cause of hyperthyroidism. However, in patients with symptoms of hyperthyroidism and increased basal serum T1 and T3 concentrations, but normal or even elevated serum TSH concentrations, TSPA should be considered in the differential diagnosis.     

The effect of the interaction of propofol and alfentanil on recall, loss of consciousness, and the Bispectral Index

The Bispectral Index (BIS) correlates well with the level of consciousness with single anesthetic drugs. We studied the effect of the interaction of propofol with alfentanil on propofol concentration and BIS associated with 50% probability of loss of consciousness and lack of recall (Cp50 and BIS50, respectively). We studied 40 consenting volunteers at two institutions who were randomly assigned to receive stepped increases of propofol (10 subjects at each site), propofol plus alfentanil 50 ng/mL (10 subjects at Emory site), or propofol plus alfentanil 100 ng/mL (10 subjects at Duke site) by using a target-controlled infusion device. Measures of sedation, BIS, deltaBIS (absolute change of BIS after a painful stimulus), memory, and drug concentration were obtained at each target drug concentration. The relation among BIS, measured drug concentration, sedation score, and presence or absence of recall was determined by linear and logistic regression for different drug regimens, and the prediction probability (Pk) was calculated. The addition of alfentanil in increasing doses did not significantly affect the BIS50 and propofol Cp50 values for loss of consciousness and lack of recall. DeltaBIS was significantly decreased by both an increase in the concentration of propofol and the presence of alfentanil. The Pk for BIS was >0.93 with all drug regimens, better than those of the target and measured propofol concentrations. We conclude that BIS correlated well with the hypnotic component of anesthesia independent of the presence of an opioid. Moreover, the level of consciousness, and, therefore, the BIS index, is affected by a painful stimulus, and this response is ablated either by opioids or increasing propofol concentration. IMPLICATIONS: In volunteers, the sedation and changes in memory function produced by propofol correlated well with changes in the Bispectral Index. This relationship was not altered by the addition of an analgesic (alfentanil). However, in moderately sedated patients who received a painful stimulus, the Bispectral Index increased, but this response was blocked by the analgesic or increasing propofol concentrations.     

The role of cytokines in bacterial pneumonia: an inflammatory balancing act

The effect of 2 mM ethanol, a concentration indicative of daily alcohol consumption, was investigated on trichloroethylene (TRI) metabolism in perfused Wistar rat liver. The study consisted of two parts: The first part studied TRI administration with or without ethanol. In the second study chloral hydrate (CH), an intermediate in TRI metabolism, was administered in the absence or presence of ethanol to phenobarbital (PB) treated or non-PB-treated rats. The concentrations of the metabolites, total trichloroethanol (TCE), and trichloroacetic acid (TCA) were measured by gas chromatography and intracellular reduced pyridine nucleotides by surface fluorometry. In the first study, ethanol infusion significantly increased the TCE/TCA ratio, TCE production rate, and percentage of reduced pyridine nucleotides, and decreased TCA production rate without an associated change in the sum of TCE and TCA formation rates. In the second study, ethanol infusion in the absence or presence of PB produced similar significant increases in the TCE/TCA ratio, TCE production rate, and percentage of reduced pyridine nucleotides, accompanied by a decrease in TCA formation. The observed shift in TRI metabolism in the presence of ethanol, from oxidation to TCA to reduction to TCE, suggests that alcohol exerts alterations in hepatic intracellular oxidation-reduction (redox) states.     

Semistructural allografting in bone defects after curettage

Amongst the focal and multifocal neuropathies that are associated with diabetes mellitus one of the most common is a proximal predominantly motor lower limb neuropathy. Recent evidence has indicated that, at least in a proportion of cases, this may have an inflammatory basis. We have examined a consecutive series of 15 cases of proximal diabetic neuropathy (diabetic amyotrophy). These were characterized by proximal pain and asymmetric proximal or generalized lower limb muscle weakness, associated in some cases with radicular sensory involvement. Two-thirds of the patients had an accompanying distal symmetric sensory polyneuropathy. Biopsy of the intermediate cutaneous nerve of the thigh, a sensory branch of the femoral nerve, showed epineurial microvasculitis in 3 patients and nonvasculitic epineurial inflammatory infiltrates in another case. In a further case, microvasculitis was found in both in the sural nerve and a quadriceps muscle biopsy specimen. The detection of inflammatory changes appeared to be correlated with the occurrence of sensory radicular involvement. Whether similar changes are present in muscle nerves in this predominantly motor syndrome requires further study. Nevertheless, the present observations confirm the view that secondary vasculitic or other inflammatory reactions may contribute to some forms of diabetic neuropathy.