Showing papers by "University of Texas Health Science Center at San Antonio published in 1989"

Long‐Term Recurrence Rates in Previously Untreated (Primary) Basal Cell Carcinoma: Implications for Patient Follow‐Up

Abstract: We reviewed all studies (since 1947) reporting recurrence rates for treatment of primary (previously untreated) basal cell carcinomas using surgical excision, radiotherapy, cryotherapy, curettage and electrodesiccation, and Mohs micrographic surgery. Our findings indicate that recurrences following treatment of primary basal cell carcinoma appear later than is generally acknowledged in the literature. We found that less than one-third of all recurrences appear in the first year following treatment; only 50% appear within the first 2 years following treatment; and only 66%, or nearly two-thirds, appear within the first 3 years following treatment. A good rule of thumb is that the 10-year recurrence rate is double, or 2 times, that of the 2-year recurrence rate. Furthermore, 18% of recurrences appear between the fifth and tenth year following treatment. These results held true, irrespective of treatment modality examined. Seventy-two studies reporting short-term recurrence rates (follow-up less than 5 years) had a weighted average recurrence rate of 4.2%, whereas 34 long-term studies (follow-up of 5 years) had a weighted average recurrence rate of 8.7%, or more than 2 times the short-term rate. Five-year recurrence rates by treatment modality are as follows: Mohs micrographic surgery 1.0%, surgical excision 10.1%, curettage and electrodesiccation 7.7%, radiation therapy 8.7%, and cryosurgery 7.5%. We conclude that the reporting of recurrence rate data for basal cell carcinoma should be standardized using 5-year life table analysis, and even more important is our conclusion that lifetime follow-up is necessary after treatment of primary basal cell carcinoma in order both recurrences and new primaries.

HER-2/neu oncogene protein and prognosis in breast cancer.

Abstract: Amplification of the HER-2/neu oncogene was recently reported to predict poor clinical outcome in node-positive breast cancer patients. Since expression of the oncogene as its protein product might be even more closely related than gene amplification to disease progression, we have now examined levels of the HER-2/neu oncogene protein for its prognostic potential in both node-positive and node-negative breast cancer. Using Western blot analysis, levels of this protein were determined in 728 primary human breast tumor specimens. We examined relationships between this protein and other established markers of prognosis, as well as clinical outcome. In node-negative patients (n = 378), the HER-2/neu protein failed to predict disease outcome. However, in node-positive patients (n = 350), those patients with higher HER-2/neu protein had statistically shorter disease-free (P = .0014) and overall survival (P less than .0001) than patients with lower levels of the protein. Higher HER-2/neu protein was found in tum...

Prediction of relapse or survival in patients with node-negative breast cancer by DNA flow cytometry.

Abstract: More accurate prediction of the prognosis in women with node-negative breast cancer may improve physicians' ability to identify the patients most likely to benefit from systematic adjuvant therapy. With this in mind, we performed DNA flow-cytometric measurements of ploidy and the fraction of cells in the synthesis phase of the cell cycle (S-phase fraction) on 395 specimens of node-negative breast cancer from our bank of frozen tumors, using the aliquots of pulverized frozen tissue from steroid-receptor assays. The median duration of follow-up in patients still alive at the time of analysis was 59 months. Thirty-two percent of the 345 specimens that could be evaluated were diploid, and 68 percent were aneuploid. The probability of disease-free survival at five years was 88 +/- 3 percent in patients with diploid tumors and 74 +/- 3 percent in those with aneuploid tumors (P = 0.02). The S-phase fraction was not a significant additional predictor of disease-free survival in patients with aneuploid tumors. However, the probability of disease-free survival in patients with diploid tumors and low S-phase fractions was 90 +/- 3 percent at five years, as compared with 70 +/- 13 percent in those with diploid tumors and high S-phase fractions (P = 0.007). Similar differences in overall survival were noted. We conclude that DNA flow-cytometric measurements of ploidy and S-phase fraction can be performed on frozen specimens of tumors and are potentially important predictors of disease-free and overall survival in patients with node-negative breast cancer.

The nature and significance of osteopontin

Abstract: Osteopontin is an acidic glycoprotein of about 41,500 daltons that has been isolated from rat, human and bovine bone. It is rich in aspartic acid, glutamic acid and serine and contains about 30 monosaccharides, including 10 sialic acids. Several types of data suggest that the carbohydrate is present as 1 N-glycoside and 5-6 O-glycosides while the phosphate is present as 12 phosphoserines and 1 phosphothreonine. The cDNA sequence indicated the presence of a Gly-Arg-Gly-Asp-Ser- (GRGDS) amino acid sequence identical to a cell binding sequence in fibronectin, and suggested that osteopontin might function as a cell attachment factor. This conclusion is supported by a number of studies showing that the protein promotes attachment and spreading of fibroblasts and osteoblasts to substratum, and that this attachment is inhibited by RGD-containing peptides. Despite this evidence that it contains an RGD recognition sequence and probably interacts with the family of receptors known as integrins, it appears that osteopontin does not possess a collagen-binding domain. Osteopontin is synthesized by preosteoblasts, osteoblasts and osteocytes, is secreted into osteoid and is incorporated into bone. The expression at an early developmental stage is an indication that osteopontin is an important component in the formation of bone. The level of synthesis of osteopontin by osteoblasts in culture is increased by treating these cells with 1,25-dihydroxyvitamin D3 and TGF-beta. The effect of these agents is at the transcriptional level. In addition to bone cells, osteopontin is synthesized by extraosseous cells in the inner ear, brain, kidney, and deciduum and placenta. It is also synthesized by odontoblasts, certain bone marrow cells and hypertrophic chondrocytes. Studies with several fibroblast and epithelial-derived cell lines in culture indicate that secretion of osteopontin can be dramatically increased when these cells are treated with phorbol esters, growth factors and hormones. However, osteopontin does not appear to be expressed by mesenchymal cells, fibroblasts, epidermal cells or by most epithelial cells in vivo.

Mohs surgery is the treatment of choice for recurrent (previously treated) basal cell carcinoma

Abstract: We reviewed all studies (since 1945) reporting recurrence rates for treatment of recurrent (previously treated) basal cell carcinomas (BCC) using surgical excision, radiotherapy, cryotherapy, curettage and electrodesiccation, and Mohs micrographic surgery. The 5-year recurrence rate for Mohs micrographic surgery is 5.6%. The recurrence rate for non-Mohs modalities of 19.9% is nearly four times higher. Individual recurrence rates for the non-Mohs modalities are 17.4% for surgical excision, 40.0% for curettage and electrodesiccation, and 9.8% for radiation therapy. There are no studies reporting 5-year data for cryotherapy. However, the recurrence rate is 13.0% for cryotherapy when the follow-up period is less than five years. The data support the following conclusions: (1) Mohs surgery is the treatment of choice for recurrent BCC; (2) if the patient is not a surgical candidate and the lesion is small, radiation therapy is an alternative that offers a better chance for cure than the other non-Mohs modalities; and (3) curettage and electrodesiccation should not be used to treat recurrent basal cell carcinoma.

Lifestyle and low-back pain. The influence of smoking and obesity.

Abstract: The authors examined associations between back pain prevalence and lifestyle factors (smoking and obesity) using national survey data. Back pain prevalence rose with increasing levels of smoking, with a relative risk of 1.47 for persons reporting 50 or more pack-years of smoking. This association was strongest in persons under the age of 45 years, however, for whom the corresponding relative risk was 2.33. There were similar trends toward greater prevalence with increasing body mass index, but prevalence rose substantially only in the most obese 20% of subjects (1.7 times higher than the lowest 20%). In a logistic regression, smoking and obesity contributed independent risk, even after controlling for age, education, exercise level, and employment status. Programs for back pain prevention may wish to test interventions for these lifestyle-related factors.

Blockade of the type I somatomedin receptor inhibits growth of human breast cancer cells in athymic mice.

Abstract: Insulin and insulin-like growth factors (IGIs) stimulate the growth of human breast cancer cells in vitro. The type I somatomedin receptor (SR) expressed in these cells may mediate the growth effects of these peptides. We have examined the role of this receptor on human breast cancer growth with a monoclonal antibody (alpha-IR-3) that blocks the receptor binding domain and inhibits IGF-I-induced growth. alpha-IR-3 inhibited clonal growth in vitro and blocked the mitogenic effect of exogenous IGF-I in both MCF-7 and MDA-231 breast cancer cell lines. Antibody-induced blockade of the type I SR also inhibited the estrogen-independent MDA-231 cells growing in vivo in nude mice, but growth of the estrogen-dependent MCF-7 cells was unaffected. IGIs are important growth regulators of MDA-231 breast cancer cells. Blockade of this growth stimulatory pathway may provide a new treatment strategy.

The Aged Rat Model of Ovarian Hormone Deficiency Bone Loss

Abstract: Three studies were carried out. First, the effects of aging on the maturation of the female skeleton were assessed. Second, the hypothesis that has linked ovarian hormone deficiency bone loss to hypercalcemic suppression of the parathyroids leading to a decrease in 1,25-dihydroxyvitamin D synthesis and gut absorption of calcium was examined. Third, the effects of ovariectomy and a combination of ovarian hormone deficiency and low dietary calcium on bone and the calcium-regulating hormones were evaluated. After 6 months, ovariectomy and a low calcium diet independently decreased the density of the ilium, the femur, and the fourth lumbar vertebra as well as the calcium content of the latter two. The effects of the two treatment regimens were additive and more marked in the vertebral bone. Ovariectomy lowered serum calcitonin only in animals fed a normal diet and had no effect on serum PTH and vitamin D metabolites, while a low calcium diet caused a significant increase in serum 1,25-dihydroxyvitamin D. In both dietary regimens ovariectomy resulted in about a 30% decrease in intestinal calcium absorption. A low calcium diet increased morphometric indices of bone formation and bone resorption as did ovariectomy, with resorption exceeding formation. The discussion of our findings led to the conclusion that the aged rat model of ovarian hormone deficiency bone loss qualifies for serious consideration as a practical convenient cost-effective animal model for exploring aspects of the pathogenesis and treatment of postmenopausal bone loss.

Effects of Interleukin-1 on Bone Turnover in Normal Mice*

Abstract: Interleukin-1 (IL-1) is a potent stimulator of osteoclastic bone resorption in vitro and causes hypercalcemia and increased osteoclastic resorption when infused into normal mice for 72 h. However, its longer term or local effects on bone turnover in vivo are unknown. To study these, we injected IL-1 alpha once daily for 3 days into the sc tissue over the calvariae of normal mice and examined its effects on calvarial bone morphology during the subsequent 4 weeks using quantitative histomorphometry. Increased bone resorption inside the calvariae and elevated plasma calcium concentrations were present 24 h after the last IL-1 injection. These early systemic effects were not prevented by indomethacin. During the following 3-4 weeks most of the bone on the injected side of the calvariae was resorbed by osteoclasts and was subsequently replaced by increased amounts of new bone. These longer term local effects on bone turnover were prevented by indomethacin. However, indomethacin did not prevent the formation of new bone inside the calvariae at sites of resorption induced by IL-1 independent of prostaglandin production. These findings indicate that IL-1 stimulates bone turnover systemically, independent of prostaglandin production, and that it has profound long term local effects on bone turnover that are mediated through prostaglandins.

Effect of anxiety on cognition, behavior, and stimulant response in ADHD.

Abstract: The effect of the comorbidity of overanxious disorder (ANX) in attention deficit hyperactivity disorder (ADHD) on laboratory measures of behavior, cognition, and stimulant response was examined. Seventy-nine children who met DSM-III-R criteria for ADHD were tested further for an oppositional defiant disorder (ODD), conduct disorder (CD), or ANX. Subjects with comorbid ANX showed less impulsiveness on a laboratory measure of behavior and had longer, sluggish reaction times on the Memory Scanning Test than those without ANX. ADHD subjects with comorbid ANX were less frequently diagnosed as CD. Forty-three of the subjects completed a double-blind trial of methylphenidate; subjects with comorbid anxiety had a significantly poorer response to the stimulant than those without anxiety, while the comorbidity of ODD or CD did not affect stimulant response. The results suggest that ADHD with comorbid ANX may represent children with primary anxiety who develop secondary inattentiveness, or they may represent a different subtype of ADHD, perhaps similar to the condition of attention deficit disorder without hyperactivity under DSM-III.

Human reticular formation: Cholinergic neurons of the pedunculopontine and laterodorsal tegmental nuclei and some cytochemical comparisons to forebrain cholinergic neurons

Abstract: Choline acetyltransferase immunohistochemistry showed that the human rostra1 brainstem contained cholinergic neurons in the oculomotor, trochlear, and parabigeminal nuclei as well as within the reticular formation. The cholinergic neurons of the reticular formation were the most numerous and formed two intersecting constellations. One of these, designated Ch5, reached its peak density within the compact pedunculopontine nucleus but also extended into the regions through which the superior cerebellar peduncle and central tegmental tract course. The second constellation, designated Ch6, was centered around the laterodorsal tegmental nucleus and spread into the central gray and medial longitudinal fasciculus. There was considerable transmitterrelated heterogeneity within the regions containing Ch5 and Ch6. In particular, Ch6 neurons were intermingled with catecholaminergic neurons belonging to the locus coeruleus complex. The lack of confinement within specifiable cytoarchitectonic boundaries and the transmitter heterogeneity justified the transmitter-specific Ch5 and Ch6 nomenclature for these two groups of cholinergic neurons. The cholinergic neurons in the nucleus basalis (Ch4) and those of the Ch5-Ch6 complex were both characterized by perikaryal heteromorphism and isodendritic arborizations. In addition to choline acetyltransferase, the cell bodies in both complexes also had high levels of acetylcholinesterase activity and nonphosphorylated neurofilament protein. However, there were also marked differences in cytochemical signature. For example, the Ch5-Ch6 neurons had high levels of NADPHd activity, whereas Ch4 neurons did not. On the other hand, the Ch4 neurons had high levels of NGF receptor protein, whereas those of Ch5-Ch6 did not. On the basis of animal experiments, it can he assumed that the Ch5 and Ch6 neurons provide the major cholinergic innervation of the human thalamus and that they participate in the neural circuitry of the reticular activating, limbic, and perhaps also extrapyramidal systems.

Evidence for the stem cell origin of hepatocellular carcinoma and cholangiocarcinoma.

Abstract: A review of the morphologic, autoradiographic, and phenotypic analysis of the cellular changes seen during induction of cancer of the liver in rats by chemical carcinogens is used to develop an alternative to the established hypothesis that chemically induced hepatocellular carcinoma arises from premalignant nodules. The authors propose that hepatocellular and ductular carcinomas arise from a pluripotent liver stem cell and that enzyme-altered foci and nodular changes are adaptive non-oncogenic responses to the toxic effects of carcinogens. It is further postulated that persistent nodules may provide an environment that nurtures development of neoplastic cells other than the altered hepatocytes that originally form the nodule. It is possible, however, that there may be more than one cellular lineage to hepatocellular cancer and that persistent nodules contain these different lineages.

Measurement of protein-DNA interaction parameters by electrophoresis mobility shift assay.

Abstract: Native gel electrophoresis (mobility shift) assays may be used to obtain quantitative information about the site distribution, equilibria and kinetics of protein-DNA interactions. These applications depend on the ability of the electrophoretic system to resolve the reaction components, and on their stabilities during the separation process Factors which affect the lifetimes and mobilities of protein-DNA complexes during electrophoresis include reaction and electrophoresis buffer composition, pH, and ionic strength; the presence of low molecular weight effectors and enzymatic substrates; the nature and concentration of the gel matrix; the temperature; the molecular weights of protein and DNA; the stoichiometric ratios of their complexes; and the possibility of conformational and configurational isomerization of reaction components. We discuss how these factors influence the acquisition of quantitative data from electrophoretic patterns and band intensities, and present formulas for the estimation of equilibrium constants and rate constants for prototypical DNA-protein interactions.

Growth Inhibition of Human Breast Cancer Cells in Vitro with an Antibody against the Type I Somatomedin Receptor

Abstract: Insulin and insulin-like growth factors (IGFs) stimulate the growth of human breast cancer cells in vitro . The type I somatomedin receptor (SR), expressed in these cells, may mediate the mitogenic effects of these peptides. We have examined the effect of type I SR blockade on human breast cancer growth with a monoclonal antibody (α-IR 3 ) that blocks the receptor binding domain. α-IR 3 inhibited binding of 125 I-IGF-I in all breast cancer cell lines tested. Binding affinity of α-IR 3 was 2 to 5 times higher than that of IGF-I in MDA-231 ( K d 2.1 nm) and MCF-7 cells ( K d 0.6 nm), respectively. In the presence of 10% calf serum, the antibody inhibited anchorage-independent growth of six of seven breast cancer cell lines. This inhibition was reversible with excess IGF-I. In serum-free medium, α-IR 3 blocked IGF-I-stimulated DNA synthesis in four of four breast cancer cell lines (MCF-7, ZR75-1, MDA-231, and HS578T). However, the antibody did not inhibit basal growth of any of the breast cancer cell lines in serum-free conditions. In three estrogen receptor-positive, estrogen-responsive breast cancer cell lines (MCF-7, ZR75-1, and T47D), type I SR blockade with α-IR 3 failed to block estrogen-stimulated DNA synthesis or cell proliferation, indicating that secreted IGF activity is not the sole mediator of the growth effects of estrogen. In conclusion, antibody-mediated type I SR blockade does not inhibit basal growth of breast cancer cells under serum-free conditions, arguing against a critical autocrine role of endogenously secreted IGF activity in vitro . However, type I SR blockade inhibits breast cancer cell growth in the presence of serum, suggesting that serum IGFs might be critical endocrine or paracrine regulators of human breast cancer.

Insulin-like growth factor-II (IGF-II): a potential autocrine/paracrine growth factor for human breast cancer acting via the IGF-I receptor.

Abstract: Insulin-like growth factor-II (IGF-II) is a potent mitogen for several types of cultured cells and tissues. We have studied the interaction of IGF-II with a panel of cultured human breast cancer cell lines, examining the possibility that these cells synthesize and secrete IGF-II activity which could have autocrine/paracrine functions. Synthetic IGF-II was mitogenic in five of seven cell lines tested, including the estrogen receptor-positive lines MCF-7L, ZR75-1, and T47D and the estrogen receptor (ER)-negative lines Hs578T and MDA-231. IGF-II was slightly less potent than IGF-I in stimulating DNA synthesis in MCF-71 cells, an effect that paralleled its ability to compete for [125I]IGF-I binding in these cells. Affinity labeling studies revealed that IGF-II could also compete for binding to the 130,000 mol wt alpha-subunit of the IGF-I receptor. A monoclonal antibody to the IGF-I receptor inhibited the mitogenic effects of IGF-II in MCF-7L and MDA-231 cells, suggesting that this receptor mediates the growth effects of IGF-II in these breast cancer cells. Using a RIA and a RRA, IGF-II-like activity was detected in conditioned medium extracts processed to remove IGF-binding proteins from several breast cancer cell lines, with the highest levels found in conditioned medium from MCF-7L and T47D cell lines. IGF-II mRNA transcripts in MCF-7L and T47D cells were identified by Northern blot analysis and were confirmed by RNase protection assay. IGF-II mRNA was increased by estrogen in MCF-7L cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Large fluctuations in body weight during young adulthood and twenty-fwe-year risk of coronary death in men

Abstract: The hypothesis that large fluctuations in weight during young adulthood are associated with increased risk of coronary heart disease was investigated by comparing the 25-year mortality of three groups of middle-aged men with distinctly different patterns of self-reported weight during young adulthood: 98 men who reported large gains and large losses, 133 who reported large gains and no losses, and 178 who reported no substantial change in weight. They were selected from a cohort of 2,107 men aged 40-56 years who participated in the Western Electric Study from 1957 through 1983. The 25-year crude risk of coronary death was 26% in the "gain and loss" group, 15% in the "gain only" group, 14% in the "no change" group, and 17% in the remaining 1,550 men. After adjustment for age and major coronary risk factors, the relative risk of coronary death in the gain and loss group as compared with the no change group was 2.0 (95% confidence interval 1.2-3.5). Risk of death from cancer was highest in the gain only group, and risk of death from all causes combined was lowest in the no change group. These results support the concept that large changes in weight during young adulthood increase the risk of coronary disease and of cancer.

Nerve growth factor receptor immunoreactive profiles in the normal, aged human basal forebrain: Colocalization with cholinergic neurons

Abstract: A monoclonal antibody raised against the receptor for nerve growth factor (NGF) has been used to map the distribution of NGF receptor-containing profiles within the human basal forebrain of four male and three female elderly patients without neurologic or psychiatric illness. Immunohistochemically processed tissue reveals a continuum of NGF receptor-positive neurons located within the medial septum, vertical and horizontal limb nuclei of the diagonal band, and nucleus basalis. NGF receptor-containing neurons are also found within the bed nucleus of the stria terminalis, the anterior commissure, the internal capsule, and the internal and external medullary laminae of the globus pallidus. Virtually all (greater than 95%) NGF receptor-containing neurons colocalize with the specific cholinergic marker choline acetyltransferase (ChAT) or the nonspecific marker acetylcholinesterase (AChE). Conversely, a few cholinergic perikarya are found which are not NGF receptor positive (and vice versa). These findings demonstrate that human basal forebrain neurons on which NGF receptor immunoreactivity is detected are primarily cholinergic and analogous to the nonhuman primate Ch1-Ch4 subgroups of Mesulam et al. (J. Comp. Neurol., 214:170-197, '83). NGF receptor-containing fiber tracts are observed emanating from the medial septum and vertical limb nucleus of the diagonal band coursing medially within the fornix. Another fascicle originating mainly from the nucleus basalis and travelling within the external capsule enroute to the cortex is observed innervating all cortical layers. Comparison of NGF receptor- and ChAT-containing neurons reveals cholinergic perikarya within the striatal complex, whereas virtually no NGF receptor-containing neurons are found in these structures. An occasional displaced NGF receptor-containing neurons is seen in the ventrolateral portion of the putamen and the white matter underlying the nucleus accumbens. These data are discussed in terms of the relationship of NGF receptor- and ChAT-containing neurons within the basal forebrain and in terms of the possible functional significance of NGF in normal and diseased brain.

Effect of loss of first-phase insulin secretion on hepatic glucose production and tissue glucose disposal in humans.

Abstract: To examine the importance of first-phase insulin secretion on total body glucose homeostasis, six normal subjects (age, 24 +/- 1 yr; ideal body wt, 100 +/- 1%) received three hyperglycemic (+75 mg/100 ml) clamp studies in combination with [3-3H]glucose: study I, 150 min hyperglycemic clamp; study II, hyperglycemic clamp plus somatostatin (6 micrograms/min) plus basal glucagon replacement (0.4 ng.kg-1.min-1) plus an insulin infusion designed to mimic only the second phase of insulin secretion; and study III, hyperglycemic clamp plus somatostatin plus basal glucagon plus an insulin infusion designed to mimic both the first and second phase of insulin secretion. Basal plasma C-peptide concentrations averaged 0.21 +/- 0.01 pmol/ml in the three study protocols. In study I the plasma C-peptide response demonstrated an early burst within the first 10 min followed by a gradually increasing phase of C-peptide secretion that lasted until the end of the study. In studies II and III plasma C-peptide declined within the first 10 min after somatostatin was started and averaged 0.06 +/- 0.01 and 0.05 +/- 0.01 pmol/min, respectively. Basal hepatic glucose production (2.3 +/- 0.2 mg.kg-1.min-1) was suppressed by 90% at 20 min and remained suppressed thereafter in studies I and III. In contrast, in study II hepatic glucose production was inhibited by only 50% (1.1 +/- 0.2 mg.kg-1.min-1) at 60 min (P less than 0.01 vs. studies I and III) and remained incompletely suppressed even after 150 min.(ABSTRACT TRUNCATED AT 250 WORDS)

Normative model for cold pressor test.

Abstract: The cold pressor test elicits an emotional/motivational pain experience from the immersion of a limb in cold water. It has been widely used to evaluate (experimental and chronic) pain. However, normative models for quantification and comparison for pain tolerance have not previously been established

Emerging fungal pathogens.

Abstract: Fungi such asFusarium spp.,Curvularia spp.,Alternaria spp. orTrichosporon beigelii, had been thought to represent contamination or harmless colonization when isolated from humans. More recently, the role of these and other newly recognized fungi as serious pathogens has been clearly established. Three diverse groups of fungi are responsible for these infections: the agents of phaeohyphomycosis and hyalohyphomycosis and certain yeasts. These infections, which have been encountered in both presumably healthy and immuno-compromised individuals, tend to be localized in the former, and disseminated and frequently fatal in the latter group of patients. A major concern is that these organisms are not uniformly susceptible to amphotericin B. Standardization of antifungal susceptibility testing may, therefore, be helpful in determining the antifungal drug of choice for each infection. It is also hoped that the advent of newer antifungals and biologic response modifiers will have a significant impact on the morbidity and mortality of these emerging infections.

Cutaneous vascular responses to isometric handgrip exercise

Abstract: Cutaneous vascular responses to dynamic exercise have been well characterized, but it is not known whether that response pattern applies to isometric handgrip exercise. We examined cutaneous vascular responses to isometric handgrip and dynamic leg exercise in five supine men. Skin blood flow was measured by laser-Doppler velocimetry and expressed as laser-Doppler flow (LDF). Arterial blood pressure was measured noninvasively once each minute. Cutaneous vascular conductance (CVC) was calculated as LDF/mean arterial pressure. LDF and CVC responses were measured at the forearm and chest during two 3-min periods of isometric handgrip at 30% of maximum voluntary contraction and expressed as percent changes from the preexercise levels. The skin was normothermic (32 degrees C) for the first period of handgrip and was locally warmed to 39 degrees C for the second handgrip. Finally, responses were observed during 5 min of dynamic two-leg bicycle exercise (150-175 W) at a local skin temperature of 39 degrees C. Arm LDF increased 24.5 +/- 18.9% during isometric handgrip in normothermia and 64.8 +/- 14.1% during isometric handgrip at 39 degrees C (P less than 0.05). Arm CVC did not significantly change at 32 degrees C but significantly increased 18.1 +/- 6.5% during isometric handgrip at 39 degrees C (P less than 0.05). Arm LDF decreased 12.2 +/- 7.9% during dynamic exercise at 39 degrees C, whereas arm CVC fell by 35.3 +/- 4.6% (in each case P less than 0.05). Chest LDF and CVC showed similar responses.(ABSTRACT TRUNCATED AT 250 WORDS)

Selective abolition of adrenergic vasoconstrictor responses in skin by local iontophoresis of bretylium.

Abstract: Skin blood flow (SkBF) in humans is controlled by a noradrenergic active vasoconstrictor system and an active vasodilator system of an uncertain neurotransmitter. Understanding how these systems interact would be aided if the vasodilator system could be studied in the absence of effects of the vasoconstrictor system. To accomplish this we combined laser-Doppler velocimetry (LDV) with the local iontophoresis of bretylium in 10 studies with eight healthy subjects. Each subject had two forearm sites (0.64 cm2) treated with bretylium to block local norepinephrine release. LDV was monitored at those sites and at two untreated sites during 3-4 min of cold stress, 35-45 min of heat stress, and a final cold stress to verify blockade. In five studies, local temperature was raised to 39 degrees C at the LDV sites before the final cold stress. Whole body skin temperature was controlled by water-perfused suits. Mean arterial pressure (MAP) was measured noninvasively. Heart rate and internal temperature were also recorded. Cutaneous vascular conductance (CVC) was calculated as LDV/MAP. During the initial cold stress, performed 130 min after bretylium treatment, CVC at treated sites fell by an average of 0.3 +/- 3.2% (P greater than 0.10) and at untreated sites by 29.2 +/- 4.1% (P less than 0.001 between sites). During heat stress, CVC at treated sites rose by 419 +/- 66% and at control sites, by 517 +/- 90% (P greater than 0.10 between sites). The internal temperature threshold for cutaneous vasodilation was not statistically different between sites (P greater than 0.10).(ABSTRACT TRUNCATED AT 250 WORDS)

The effects of therapeutic ultrasound on tendon healing: a biomechanical study

Abstract: The effect of 1 MHz therapeutic ultrasound on the healing strength of tendons was studied in the tenotomized, repaired and immobilized right Achilles tendons of 26 rabbits. Twelve tendons were sonicated daily in continuous waves at a spatial averaged intensity of 1 W cm(2) [corrected] for 5 min. After nine consecutive treatments, the tendons were excised under anesthesia and compared biomechanically. Exposure to ultrasound induced a significant increase in both the tensile strength and the energy absorption capacity of the tendons. Although healing in rabbits may not translate directly to healing in humans, these findings suggest that surgically repaired human Achilles tendons may heal faster if ultrasound is applied during the early stages of healing.

Initial Characterization of Cells Derived from Human Periodontia

Abstract: The studies presented in this report describe an initial characterization of cell types derived from explants of human periodontia. Cell cultures were established from human periodontal ligament (PL4, PL7), gingival tissue (GF2), and alveolar bone (BP1) by means of explant techniques and monolayer culture. Cells were studied at passage numbers 2-4 and were characterized on the basis of morphological, biochemical, and proliferative parameters. Subconfluent cells did not have distinct morphologies useful in distinguishing them from one another. At confluence, PL4 and BP1 cells formed multilayered cultures of randomly oriented cells, while PL7 and GF2 cells grew in a monolayer of parallel cells. Biochemically, PL4 and BP1 cells exhibited characteristics consistent with an osteoblast-like phenotype. These included a significant increase in PTH-stimulated cyclic AMP and high basal levels of alkaline phosphatase activity, which were decreased on exposure to PTH and increased after stimulation by 1.25 dihydroxyvitamin D3. In contrast, PL7 and GF2 cells exhibited basal alkaline phosphatase levels that were low, and cyclic AMP levels were not modulated by PTH stimulation. Cell populations PL7 and GF2 did not proliferate in culture medium supplemented with 3% platelet-poor plasma. After the addition of platelet-derived growth factor (PDGF) to this medium, the proliferation of these cell populations was equal to that in media supplemented with 10% fetal bovine serum. In contrast, PL4 and BP1 cells did proliferate in culture medium supplemented with 3% platelet-poor plasma. The addition of PDGF to the medium resulted in only a moderate increase in the proliferation of cell populations PL4 and BP1.(ABSTRACT TRUNCATED AT 250 WORDS)

Trichomonas vaginalis surface proteinase activity is necessary for parasite adherence to epithelial cells.

Abstract: The role of cysteine proteinases in adherence of Trichomonas vaginalis NYH 286 to HeLa and human vaginal epithelial cells was evaluated. Only pretreatment of trichomonads, but not epithelial cells, with N-alpha-p-tosyl-L-lysine chloromethyl ketone (TLCK), an inhibitor of trichomonad cysteine proteinases, greatly diminished the ability of T. vaginalis to recognize and bind to epithelial cells. Leupeptin and L-1-tosylamide-2-phenylethyl chloromethyl ketone, other cysteine proteinase inhibitors, also decreased T. vaginalis cytadherence. Parasites incubated with TLCK and washed extensively still did not adhere to cells at levels equal to those seen for control trichomonads treated with phosphate-buffered saline or culture medium alone. Exposure of TLCK-treated organisms with other cysteine proteinases restored cytadherence levels, indicating that proteinase action on the parasite surface is prerequisite for host cell attachment. Concentrations of TLCK which inhibited cytadherence did not alter the metabolism of T. vaginalis, as determined by metabolic labeling of trichomonad proteins; the protein patterns of T. vaginalis in the presence and absence of TLCK were identical. Kinetics of TLCK-mediated inhibition of cytadherence of other T. vaginalis isolates with different levels of epithelial-cell parasitism were similar to the concentration-dependent inhibition seen for isolate NYH 286. Incubation of TLCK-treated, washed organisms in growth medium resulted in regeneration of adherence. Finally, treatment of T. vaginalis organisms with proteinase inhibitors for abrogation of cytadherence effectively rendered the trichomonads unable to kill host cells, which is consistent with the contact-dependent nature of host cytotoxicity. These data show for the first time the involvement of T. vaginalis cysteine proteinases in parasite attachment to human epithelial cells. These results have implications for future pharmacologic intervention at a key step in infection.