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Biomedical subjects

R Schultz

Publications and source records attributed to R Schultz.

At least 55 records · Page 3Linked to original sources

Enhancement of selectivity in recognition of nucleic acids via chemical autoligation.

A new approach to increase the selectivity of interaction between oligonucleotide probes and target nucleic acids is described. In place of a single, relatively long oligonucleotide probe, two or three short oligomers terminated by thiophosphoryl and bromoacetamido groups are employed. Fast and efficient autoligation takes place when the oligomers hybridize in a contiguous mode to the same complementary strand such that a thiophosphoryl group on one strand and a bromoacetamido group on another are brought into proximity. A single nucleotide mismatch for the short probes leads to marked reduction in the rate of autoligation. The binding affinity of the product is close to that for a natural probe of the same length. This approach could have potential in oligonucleotide-based diagnostics, chemical amplification systems, and therapeutic applications.

Base Composition↗

Altered energy balance may account for growth failure in Rett syndrome.

To determine whether alterations in energy balance account for growth failure in Rett syndrome, we measured dietary energy intakes, fecal fat losses, activity patterns, and sleeping as well as quietly and actively awake metabolic rates in Rett syndrome girls and healthy controls. Dietary energy intakes and fecal fat losses did not differ between the groups. Metabolic rates while sleeping and quietly awake were 23% lower (P < .05) in Rett syndrome girls than in controls; metabolic rates while actively awake did not differ between the groups. However, because of the 2.4-fold greater time (P < .001) spent in involuntary motor movement, energy expenditure associated with activity was twofold greater (P < .05) in Rett syndrome girls than in controls. Although total daily energy expenditure of the two groups did not differ significantly, energy balance was less positive in the Rett syndrome girls than in the controls. This small difference in energy balance, if sustained over months to years, is sufficient to account for growth failure in Rett syndrome girls.

Anthropometry↗

[Primary cytomegalovirus infection in pregnant women of different socioeconomic status].

Cytomegalovirus infection is the first cause of viral congenital infections. We studied the incidence of primary cytomegalovirus infection, searching for the presence of antibodies with an ELISA technique, in 939 pregnant women of a low socioeconomic level, attending a public outpatient clinic and 123 pregnant university students, attending a special outpatient clinic for students. The initially seronegative women were tested again during the second and third trimester of pregnancy to identify primary infections. The presence of cytomegalovirus congenital infection in the newborns of infected mothers was investigated isolating the virus in cell cultures from urine samples. There was a higher prevalence of infection among low socioeconomic status women (95 vs 69.9%). Two women (one student and one coming from a low socioeconomic status) had a primary infection and in the newborn of the student, a congenital cytomegalovirus infection was detected. It is concluded that women's socioeconomic condition is not a risk factor for cytomegalovirus primary infection during pregnancy.

Adult↗

Follow-up of pregnant women at high risk of transmitting herpes simplex virus.

Prospects for neonatal herpes transmission were studied in a group of pregnant Chilean women at high herpetic risk--including 59 with a history of genital herpes, 11 with a first genital herpes episode during the observed pregnancy, and 16 whose sexual partners had a history of genital herpes. Each woman completed a survey questionnaire, provided serologic samples for detection of herpes simplex virus (HSV), and provided periodic samples taken with cotton swabs for HSV isolation. The 86 women who completed the study had an average age of 28 years; most (58.8%) were primiparas. Only 21 of the 86 subjects yielded HSV isolates (predominantly HSV-2) from weekly cotton swab samples taken from the 34th week of pregnancy onward. HSV-2 predominance was found both in the symptomatic cases and in the three asymptomatic ones. Of six subjects found to be shedding HSV at the time of delivery, only one exhibited asymptomatic shedding. These findings are consistent with the following conclusions derived from studies in developed countries: (1) Isolation of HSV in pregnancy does not define a greater risk of shedding HSV during childbirth. (2) In nearly all (five of six) cases, HSV shedding during childbirth involved symptomatic episodes of herpes that clearly defined the steps to be taken by the physician. (3) Despite this, the finding of one asymptomatic case demonstrates that the physician should request a test for HSV isolation at the time of delivery by a woman at high herpetic risk.

Female↗

Proteolysis results in altered leak channel kinetics and elevated free calcium in mdx muscle.

Resting free calcium levels ([Ca2+]i) are elevated in Duchenne human myotubes and mdx mouse muscle and myotubes which lack the gene product dystrophin at the sarcolemma. Increased net muscle protein degradation has been directly related to this elevated [Ca2+]i. The [Ca2+]i rise may result from increased calcium influx via leak channels, which have increased opening probabilities (Po) in dystrophic cells. Dystrophin, therefore, might directly regulate leak channel activity. In intact mdx soleus muscles, protein degradation was reduced to normal levels by leupeptin, a thiol protease inhibitor. In muscle homogenates, leupeptin also abolished calcium-induced increases in protein degradation. When mouse myotubes were cultured in the continuous presence of leupeptin (50 microM), the elevation in mdx resting [Ca2+]i was prevented. Leak channel Po increased with age in mdx myotubes, whereas leupeptin-treated mdx leak channel opening probabilities were always lower or equal to the Po for untreated normal myotubes. These results indicate that increased leak channel activity in dystrophic muscle results in elevated [Ca2+]i levels, but also suggest that dystrophin does not directly regulate channel activity. Instead the results suggest that proteolysis may be responsible for the altered gating of calcium leak channels. The resultant increased channel Po in turn elevates [Ca2+]i, which further increases proteolytic activity in a positive feedback loop, leading to the eventual necrosis of the muscle fibers.

Animals↗

Localization of the glucocorticoid receptor in testis and accessory sexual organs of male rat.

Localization of glucocorticoid receptor-like immunoreactivity (GR-LI) was studied in adult rat testis, epididymis, ejaculatory duct, seminal vesicle and prostate by light and electron microscopic immunocytochemistry. In the interstitium of the testis GR-LI was seen in the nuclei of Leydig cells, macrophages, fibroblasts, smooth muscle cells and endothelial cells of blood vessels. Furthermore, GR-LI was observed in zygotene and early pachytene primary spermatocytes of some seminiferous tubules during stages XIII-XIV and I-III of the spermatogenic cycle. Other spermatogenic cells and Sertoli cells were devoid of staining. GR-LI was also found in peritubular myoid cells, fibroblasts and basal cells of the epididymis, vas deferens and prostate. Localization of GR-LI in primary spermatocytes and Leydig cells suggests that glucocorticoids directly affect spermato- and steroidogenesis in the testis. The absence of GR-LI from functional, stromal cells of the male accessory sexual organs suggests that they are not targets for glucocorticoid hormones.

Animals↗

Safety of thrombolytic therapy in elderly patients with massive pulmonary embolism: a comparison with nonelderly patients.

OBJECTIVES: The aim of the study was to prospectively estimate the safety of thrombolytic therapy in elderly patients with massive pulmonary embolism in comparison with that in nonelderly patients. BACKGROUND: In massive pulmonary embolism, lysis of thrombi can be achieved faster with thrombolytic therapy than with conventional heparin therapy, but it is administered with great caution in elderly patients because the risk of bleeding is thought to be higher than in nonelderly patients. Yet, thrombolytic therapy might be of value in elderly patients also, in allowing potentially more rapid improvement than is achieved with conventional heparin therapy. METHODS: Eighty-nine patients with massive pulmonary embolism defined as Miller score > or = 17/34 underwent thrombolytic therapy without consideration of age if they had no contraindication for such treatment. Fifty-three patients were < or = 70 years old (mean age +/- SD 54 +/- 15 years; range 18 to 70), and 36 patients were > or = 71 years old (78 +/- 5 years; range 71 to 88). Except for mean age, there were no significant differences between the two treatment groups, particularly in terms of clinical presentation, average Miller score and pulmonary artery pressure regimen. Thrombolytic therapy was administered in the form of streptokinase at a dose of 100,000 IU/h over 12 h, with an initial injection of 250,000 IU over 15 min. Heparin was introduced 12 h after initiation of thrombolytic therapy. Urokinase or tissue-type plasminogen activator was used only in case of contraindication to streptokinase. RESULTS: The frequency of uncomplicated clinical course was the same in both treatment groups. Surgical embolectomy was necessary in three nonelderly patients (5.6%) and one elderly patient (2.7%). Changes in pulmonary pressure regimen and Miller score were identical in both groups. Three patients died during the in-hospital course: two nonelderly patients (3.7%) and one elderly patient (2.7%). Minor bleeding occurred in five nonelderly (9.4%) and five elderly (13.8%) patients (p = 0.74). Major bleeding was observed in three nonelderly (5.6%) and five elderly (13.8%) patients (p = 0.29). Bleeding subsequent to early invasive procedure accounted for six (75%) of eight patients with major bleeding: two nonelderly patients (one of whom died) and four elderly patients. No intracranial hemorrhage was observed. No predisposing factor for bleeding was identified, except the need for early vascular access for pulmonary angiography through the femoral approach or for percutaneous insertion of an intracaval device for partial interruption of the inferior vena cava. CONCLUSIONS: Thrombolytic therapy administered for massive pulmonary embolism in patients free of contraindication yields similar results and carries a similar risk for bleeding complications in elderly compared with nonelderly patients. Limiting early invasive procedures may result in less frequent major bleeding complications.

Adolescent↗

Elevated post-stimulatory intracellular adenosine 3,5-cyclic monophosphate (cAMP) levels are found in peripheral blood cells after ABMT.

Intracellular cyclic adenosine monophosphate (cAMP) levels were measured in the peripheral mononuclear cells of 25 recipients of ABMT after stimulation with forskolin (10(-4) M), cholera toxin (1 microgram/ml) and prostaglandin E2 (PGE2, 10(-6) M). Significantly increased post-stimulatory cAMP levels were found in cells derived from patients' cells less than 30 days after ABMT (after forskolin stimulation: mean 89.7 +/- 45.4 pmol per 5 x 10(6) cells, p < 0.001; after cholera toxin stimulation: mean 78.6 +/- 37.9 pmol per 5 x 10(6) cells, p = 0.003; after PGE2 stimulation: mean 93.6 +/- 36.6 pmol per 5 x 10(6) cells, p < 0.001). However, at a later time after ABMT (7-60 months), cAMP levels had returned to normal and no significant differences in intracellular cAMP content between cells from patients and normal individuals could be detected. In addition, in six patients cAMP levels after PGE2 stimulation were measured serially pre- or peri-transplantation up to a time when haematologic recovery had occurred: the significantly elevated inducible cAMP levels found early post-ABMT returned to normal with peripheral blood reconstitution. This observation could be of interest in the post-transplantation period, because cAMP, as a 'second messenger', is a modulator of the immune system.

Adolescent↗

Expression of beta-nerve growth factor and its receptor in rat seminiferous epithelium: specific function at the onset of meiosis.

beta-Nerve growth factor (NGF) is expressed in spermatogenic cells and has testosterone-downregulated low-affinity receptors on Sertoli cells suggesting a paracrine role in the regulation of spermatogenesis. An analysis of the stage-specific expression of NGF and its low affinity receptor during the cycle of the seminiferous epithelium in the rat revealed NGF mRNA and protein at all stages of the cycle. Tyrosine kinase receptor (trk) mRNA encoding an essential component of the high-affinity NGF receptor was also present at all stages. In contrast, expression of low affinity NGF receptor mRNA was only found in stages VIIcd and VIII of the cycle, the sites of onset of meiosis. The low-affinity NGF receptor protein was present in the plasma membrane of the apical Sertoli cell processes as well as in the basal plasma membrane of these cells at stages VIIcd to XI. NGF was shown to stimulate in vitro DNA synthesis of seminiferous tubule segments with preleptotene spermatocytes at the onset of meiosis while other segments remained nonresponsive. We conclude that NGF is a meiotic growth factor that acts through Sertoli cells.

Animals↗

The laser Doppler analysis of posturally induced changes in skin blood flow at elevated temperatures.

Recently, it has become possible to use laser Doppler techniques to separately quantitate the two components of blood flow, microvascular volume and red blood cell velocity. We used these techniques in 21 normal volunteers to quantitate the effect of postural changes in skin blood flow and its components at 35 degrees C and at 44 degrees C. Postural skin blood flow changes have ben studied extensively at basal skin temperature, but not at elevated temperatures. We contrasted changes at sites with arteriovenous anastomotic (AVA) blood flow (toe and finger pulps) with changes at sites with primarily nutritive flow (elbow and knee). Skin blood flow increased markedly with increasing temperature. The increases at the elbow and knee were the products of equivalent increases in both microvascular volume and velocity. In contrast, the increases on the finger and toe pulps were mainly due to increases in velocity. Elevation of both upper and lower extremities brought about a decrease in skin blood flow. Dependency increased blood flow. The magnitudes of observed changes were greater on the lower extremity than on the upper extremity and greater at 44 degrees C than at 35 degrees C. Once again, with postural change, the nutritive areas exhibited similar changes in volume and velocity while the AVA areas primarily showed velocity alterations. The correlation of systolic pulse pressures with blood flow was greater at the AVA areas than at nutritive areas and greater at 44 degrees C than at 35 degrees C. This correlation was with the velocity rather than with the volume component.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Expression of diazepam binding inhibitor-like immunoreactivity in rat testis is dependent on pituitary hormones.

Diazepam binding inhibitor-like immunoreactivity (DBI-LI) in normal and hypophysectomized (HPX) rat testis was studied by light and electron microscopic immunohistochemistry. In normal testis DBI-LI was observed in interstitial Leydig cells and Sertoli cells of most seminiferous tubules. At the electron microscopic level, DBI-LI was distributed throughout the cytoplasm of labeled cells; a concentration of the labeling product was observed in the smooth endoplasmic reticulum, Golgi apparati, and the outer membrane of the mitochondria. In the seminiferous epithelium, labeled processes of Sertoli cells could be traced among developing germ cells. After HPX a gradual disappearance of DBI-LI was observed in all Leydig cells. The number of labeled Sertoli cells was reduced in the majority of tubules after HPX, whereas in some tubules the staining was only slightly reduced. Replacement therapy of the HPX animals with human CG prevented the disappearance of DBI-LI from Leydig cells, whereas replacement with FSH did not prevent the disappearance of DBI-LI in Leydig cells. In Sertoli cells replacement therapies were not effective in restoring DBI-LI. In rat testis DBI and mitochondrial benzodiazepine binding sites are highly concentrated in the Leydig cells. Mitochondrial benzodiazepine binding sites and DBI are involved in the regulation of steroid production. As the expression of DBI-LI is under the control of pituitary hormones, DBI may play a role as an endogenous regulator of intracellular metabolic functions, such as steroidogenesis, in rat testis.

Animals↗

Genitourinary tract infections in pregnancy and low birth weight: case-control study in Australian aboriginal women.

OBJECTIVE: To investigate the association between genital and urinary tract infections in pregnant Aboriginal women and low birth weight. DESIGN: Retrospective case-control study controlling for potential confounding variables. SETTING: Western Australia from 1985 to 1987. SUBJECTS: All Aboriginal women (n = 269) who had given birth to singleton infants weighing 2250 g or less (cases), and 269 randomly selected Aboriginal women who had given birth to singleton infants weighing 3000 g or more (controls). MAIN OUTCOME MEASURES: Proportions of women in case and control groups who had had genital and urinary tract infections; odds ratios for low birth weight when genitourinary tract infection was present; population attributable fraction of low birth weight to genitourinary tract infection. RESULTS: At the time of delivery 51% of women in the case group (109/215) had genitourinary tract infections compared with 13% of controls (35/266). After controlling for potential confounding variables the odds ratio for giving birth to infants weighing 2250 g or less when genitourinary tract infection was present was 4.0 (95% confidence interval 2.3 to 7.0). The proportion of infants with low birth weight attributable to genitourinary tract infection in the whole population of Aboriginal women was 32% (95% confidence interval 17% to 49%). CONCLUSIONS: There was a strong association between low birth weight and the presence of genitourinary tract infections in Aboriginal women both during pregnancy and at the time of delivery. A community intervention trial of screening and treatment of genitourinary infections in this population is recommended.

Case-Control Studies↗

Vision research in departments of ophthalmology. An Association of University Professors of Ophthalmology perspective.

A research committee of the Association of University Professors of Ophthalmology disseminated a survey questionnaire to determine the state of research in departments of ophthalmology across the United States. The questionnaire contained 71 questions that were designed to assess attitudes and trends within members' departments and to solicit suggestions from the membership. Of the 145 members and affiliates queried, 140 responded. While the results of the survey indicate significant diversity among departments, departmental chairpersons view research as a major priority in the goals of their departments, and they envision maintenance or expansion of research over the next decade. The survey results have been collated and serve now as the basis for this Association of University Professors position article.

Humans↗

Immunohistochemistry of diazepam binding inhibitor (DBI) in the central nervous system and peripheral organs: its possible role as an endogenous regulator of different types of benzodiazepine receptors.

The distribution of diazepam binding inhibitor (DBI), a multi-function peptide which has recently been discovered, was studied in the rat and human central nervous system and in peripheral organs of the rat by light and electron microscopical immunohistochemistry. In the central nervous system, DBI-LI was localized in many glial cells and glial tumors, and in some neurons. In the periphery, DBI-LI was found in many tissues but it was expressed selectively in specialized cell types. Intense DBI-LI was observed in some endocrine, steroid-producing cells such as glomerular cells of the adrenal gland and Leydig cells of the of the testis. Different types of epithelial cells, for instance distal convoluted tabular cells of the kidney and mucosal cells of the small intestine, displayed moderate DBI-LI. Some supporting cells, such as Schwann cells and Sertoli cells, were also immunopositive. The frequent localization of DBI in cells, also known to contain large amounts of mitochondrial benzodiazepine receptors, indicates that DBI may play an important role as an endogenous regulator of intracellular metabolic functions via the mitochondrial benzodiazepine receptor.

Adrenal Glands↗