Search

We present a pulsed fiber laser system with average power up to 265 W, pulse energy up to 10.6 mJ, pulse duration adjustable in the range 500 ps–500 ns, repetition rate fully controllable from single-shot operation up to 1 MHz, and the ability to control peak power independently of pulse energy. The system has a compact, all-spliced construction. Such a versatile laser will have wide applications in materials processing.

To investigate clinical and economic consequences following generic substitution of one vs multiple generics of topiramate (Topamax; Ortho-McNeil Neurologics, Titusville, NJ).

ABSTRACTWe have evaluated the Platelia Aspergillusenzyme immunoassay for detection of galactomannan in bronchoalveolar lavage (BAL) specimens in solid organ transplant patients with aspergillosis. The precision and reproducibility in serum or BAL to which galactomannan was added were similar. Sensitivity was 81.8% in patients with aspergillosis, and specificity was 95.8% in lung transplant patients who underwent BAL for surveillance for infection or rejection. Among transplant controls, positive results were more common in patients (i) who underwent diagnostic BAL performed for evaluation of symptoms or chest computed tomographic abnormalities, (ii) who had undergone lung transplantation, or (iii) who were colonized with Aspergillus. Galactomannan testing in BAL is useful for diagnosis of aspergillosis in transplant patients. The significance of positive results in patients without confirmed aspergillosis requires further evaluation.

CD40 ligand-CD40 ligation is important in the development of T-cell-mediated immune responses. The purpose of this study was to examine the role of CD40L in recovery from histoplasmosis using a murine model of intratracheally induced infection. B6C3F1mice were infected intratracheally with Histoplasma capsulatumyeast and monitored for clearance of the organism from the lungs and spleen. CD40L treatment was begun on either day-2 or +2 post inoculation and continued until day 14 in CD4-depleted animals and from day-2 to day +4 in nonimmunosuppressed animals. Amphotericin B treatment was begun four days following inoculation and given every other day for 10 days. CD40L reduced fungal burden by less than one log when started two days before infection but did not act synergistically with low-dosage amphotericin B (0.2 mg kg-1qod) in CD4 depleted mice. Low-dose amphotericin B, CD40L, and the combination of the two failed to lower the fungal burden in a second experiment using a more virulent isolate of the same strain of H. capsulatumin CD4-depleted mice. Furthermore, CD40L did not increase the concentrations of IFN-γ, IL-12 or IL-10 in the lungs or spleens of infected animals. In summary, CD40L had minimal or no effect on the course of infection in this murine model of histoplasmosis.

Objectives to assess the quality of life of patients undergoing sapheno-femoral junction (SFJ) ligation and long saphenous vein stripping (LSV), using two different techniques. Design prospective, randomised trial. Materials and methods eighty patients were recruited and randomised to either Perforate Invagination (PIN) stripping (43) or Conventional stripping (37). Patients completed the Short Form 36 (SF-36) and EuroQol (EQ) questionnaires preoperatively, and postoperatively at 6 weeks and 6 months. Results bodily pain, role function and physical summary were significantly improved at 6 months in the PIN stripping group. In the Conventional group, bodily pain and physical function were similarly improved, but not role function. EQ global quality of life was significantly and progressively improved at 6 weeks and 6 months in the PIN group (global score

To assess the accuracy of the ten questions screen as a measure of childhood disability for epidemiologic studies in populations lacking resources for professional assessment of children's development and functioning.

We analyzed the gestational, parturitional, neonatal (GPN) histories of 281 severely mentally retarded patients with cerebral palsy to define the etiology or pathogenesis of cerebral palsy in each patient. No association between type of cerebral palsy and GPN histories was found except for an increase in spastic-athetoid patients in the breech delivery subgroup. Significant findings include: increased incidence of prematurity and postmaturity, small and large for-gestational age (GA) fetal size, a normal birthweight for GA distribution of patients with diabetic mothers, an excess of mothers =35 and =20 years old, an increased immediately-previous sib interval of 2.59 years suggestive of an “infertility factor”, an unremarkable GPN history in one third of the cases, in another one third GPN problems not usually associated with a high risk of CNS damage, and in one third gross complications which were probably responsible for the CP, including: an increased incidence of breech deliveries, twinning, prolonged and precipitous labor and placental complications; no increased association of athetosis and Rh incompatibility or incidence of toxemia was found. Disseminated intravascular coagulation due to prenatal death of a twin may have been the cause of brain damage in several patients.

Entactin is a widely distributed basement membrane sulfated glycoprotein of approximately equal to 150 kDa. The entactin gene is expressed early in mouse embryogenesis. Two cDNA clones complementary to rat entactin mRNA were isolated by antibody screening of an oligo(dT)-primed cDNA library constructed in the lambda gt11 expression vector. One of the clones, lambda 1E, was subcloned into plasmid pBR322 and further characterized. The clone contained sequences complementary to an mRNA species 6 kilobases in length. This mRNA was translated in rabbit reticulocyte lysates to yield a polypeptide of 143 kDa that was precipitated with anti-entactin antiserum. The cDNA insert, 1328 base pairs long, was sequenced and found to contain an open reading frame of 729 base pairs that coded for 243 amino acids at the carboxyl terminus of entactin. Analysis of the peptide revealed no extended alpha-helical or beta-sheet secondary structures. Radiolabeled probes prepared by nicktranslation of p lambda 1E were used to monitor the steady-state levels of entactin mRNA in F9 embryonal carcinoma cells that were induced to differentiate by exposure to retinoic acid and dibutyryl cyclic AMP. The increase in steady-state levels of entactin mRNA lagged behind the increase in mRNA for the B2 chain of laminin, suggesting that laminin and entactin are independently rather than coordinately regulated.

Nine antimicrotubule benzimidazole derivatives tested in a Pneumocystis carinii culture system with human embryonic lung fibroblast monolayers inhibited organism proliferation. The concentrations of drugs inhibitory in culture ranged from 10 to 0.1 micrograms/ml, with thiabendazole being the least effective (10 micrograms/ml) and parbendazole being the most effective (0.1 microgram/ml). The parent compound, benzimidazole, was inactive at 10 micrograms/ml. Demonstration that this group of compounds has activity against P. carinii provides a new potential target that can be exploited, the microtubules. Also, the variability in the effectiveness of the compounds provides the basis for studies of structure-activity relationships, which were initiated in this study.

The combination of primaquine with clindamycin is effective in both in vitro and in vivo models of Pneumocystis infection. Primaquine alone at concentrations from 10 to 300 micrograms/ml reduced the numbers of organisms in cultures to less than 7% of control. Significant inhibition was observed down to 0.1 microgram/ml. Clindamycin at 5 micrograms/ml was ineffective alone. Combinations of clindamycin and primaquine in culture at various concentrations were effective, but there was no evidence of true synergy. In rats with established Pneumocystis pneumonia, clindamycin alone at 5 or 225 mg/kg was ineffective. Primaquine alone at 0.5 or 2 mg/kg did not significantly affect the numbers of organisms remaining. The combination of 0.5 mg of primaquine per kg and 225 mg of clindamycin per kg was effective for therapy, lowering the numbers of organisms in the lungs by about 90%. The combination of 2 mg of primaquine per kg and 225 mg of clindamycin per kg was more effective, lowering the numbers of organisms by almost 98%. In the in vivo prophylaxis model, primaquine at 0.1 or 0.2 mg/kg did not prevent the development of Pneumocystis pneumonia in immune-suppressed rats. Clindamycin at 50 mg/kg had a modest effect alone, but at 5 mg/kg all animals became heavily infected. At 0.5 mg/kg, primaquine alone reduced the severity of infection, but seven of eight rats were still infected. In contrast, the combination of 5 mg of clindamycin per kg and 0.5 mg of primaquine per kg prevented infection in 8 of 10 rats; 2 rats had minimal infection. These studies suggest that the combination of clindamycin and primaquine should be tested in therapy or prophylaxis of Pneumocystis infections in humans.

Trimetrexate and BW301U (piritrexim isethionate), lipid-soluble inhibitors of dihydrofolate reductase, are potent inhibitors of the growth of Pneumocystis carinii in culture with WI-38 cells. Inhibition was observed with 0.1 microgram of trimetrexate or BW301U per ml. Trimethoprim is ineffective at 100 micrograms/ml in this culture system. Both trimetrexate and BW301U were effective as prophylactic agents against P. carinii pneumonia in rats; trimetrexate at 7.5 mg/kg protected 9 of 10 rats, and BW301U at 5 mg/kg protected 4 of 10.

The use of two statistical methods to quantify time trends (Poisson regression and time series analysis) is illustrated in analyses of changes in child injury incidence after implementation of a community-based injury prevention program in Central Harlem, New York City. The two analytical methods are used to quantify changes in the rate of injury following the program, while taking into account the underlying annual and seasonal trends. Rates of severe injury during the period from 1983 to 1991 among children under the age of 17 years living in Central Harlem and in the neighboring community of Washington Heights are analyzed. The two methods provide similar point estimates of the effect of the intervention and have a good fit to the data. Although time series analysis has been promoted as the method of choice in analysis of sequential observations over long periods of time, this illustration suggests that Poisson regression is an attractive and viable alternative. Poisson regression provides a versatile analytical method for quantifying the time trends of relatively rare discrete outcomes, such as severe injuries, and provides a useful tool for epidemiologists involved with program evaluation.

An enzyme-linked immunosorbent assay (ELISA) to quantitate Pneumocystis carinii organisms from culture supernatant and rat lung has been developed. A polyclonal antibody specific to P. carinii was produced in Sprague-Dawley rats by allowing P. carinii-infected animals to recover from infection. This antibody reacted strongly to P. carinii proteins of 50 to 55 kDa and weakly to those of 33 and 116 kDa. The ELISA used this convalescent-phase antibody to quantitate the number of P. carinii organisms in lung homogenates of infected rats and supernatants from infected tissue cultures which were used to screen drugs for P. carinii. The results of the ELISA were compared with those of direct microscopic counting of organisms, and the two methods were highly correlated (r > 0.9). Thus, the ELISA can be used as an alternative method for the quantitation of P. carinii organisms, and it is superior to the conventional microscopic method because it is easier to perform and less labor-intensive.

An intronless gene encoding an additional human serotonin (5-HT) 5-HT1-like receptor subtype was isolated from a human genomic library with probes obtained from degenerate PCR primers used to amplify 5-HT-receptor-specific sequences. The highest degree of homology was found with the 5-HT1E subtype (70%) and the 5-HT1D alpha (63%) and 5-HT1D beta (60%) receptors. RNA for this gene was detected in the human brain but was not detected in kidney, liver, spleen, heart, pancreas, and testes. High-affinity (Kd = 9.2 nM) 3H-labeled 5-HT binding was detected. Competition studies revealed the following rank order of potencies for serotonergic ligands: 5-HT > sumatriptan >> 5-carboxyamidotryptamine > 8-hydroxy-2(di-1-propylamino)tetralin > spiperone. 5-HT produced a dose-dependent inhibition of forskolin-stimulated cAMP accumulation (EC50 = 7.9 nM) in transfected cells. These properties distinguish this receptor from any previously characterized and establish a fifth 5-HT1-like receptor subtype (5-HT1F) coupled to the inhibition of adenylate cyclase.

It is known that primary (swallow-induced) esophageal contractions are abnormal in alcoholics. Data concerning acid-induced esophageal contractions, which appear to be important in cleansing refluxed acid from the esophagus, are lacking. To determine whether acid-induced esophageal contractions are also affected by chronic ethanol exposure, we studied secondary (acid or saline-induced) esophageal motor events in 19 male alcoholics [6 actively drinking (ADA), 13 withdrawing (WA)]. Esophageal motility was performed in response to wet swallows (5 ml of water) and to intraesophageal injection of 5 ml of 0.1 N HCl (0.1 N) or saline. Lower esophageal sphincter pressure (LESP), amplitude (ECA), duration (ECD), and velocity (ECV) of esophageal contractions in response to swallowing and injection of acid or saline were similar in controls and alcoholics. There were more simultaneous and double-peaked contractions in response to acid and saline than to swallows in both alcoholics and controls. However, there was no difference between HCl- and NaCl-induced contractions. ECA in alcoholics was significantly higher than in controls. ECD in alcoholics was significantly more prolonged than in controls. There was no significant different between alcoholics and controls in ECV, LESP, or LES relaxation. These data indicate that similar to primary esophageal contractions, secondary esophageal contractions are also abnormal in both actively drinking and withdrawing alcoholics.

To investigate the frequency and severity of esophagitis and esophageal dys-motility in patients with chronic spinal cord injury (SCI), 46 males with chronic SCI completed a questionnaire regarding gastrointestinal symptomatology. Eleven of these patients subsequently underwent upper gastrointestinal (GI) endoscopy with esophageal biopsies and 10 of the 11 also had esophageal motility studies. A significantly higher percentage of SCI patients experienced heartburn (SCI 61%; controls (C) 40%), esophageal chest pain (SCI 33%; C 6.4%), and intermittent dysphagia (SCI 30%; C 8.5%). Forty-five percent of SCI patients had endoscopic evidence of mild esophagitis, and 91% of them had histologic evidence of esophagitis. SCI patients had low amplitude, slowly propagating abnormal (double-peaked) peristatic esophageal contractions. We conclude that SCI patients experience significantly more esophageal symptoms than controls. They have a higher incidence of esophagitis and esophageal motor abnormalities. The clinical relevance of these abnormalities remains to be evaluated.

We have determined the structural organization of the human and mouse genes that encode the laminin beta2 chain (s-laminin), an essential component of the basement membranes of the neuromuscular synapse and the kidney glomerulus. The human and mouse genes have a nearly identical exon-intron organization and are the smallest laminin chain genes characterized to date, due to the unusually small size of their introns. The laminin beta2 chain genes of both species consist of 33 exons that span

A method of growing rat Pneumocystis carinii with human embryonic lung fibroblasts (HEL-299 cells) sheeted onto microcarrier beads has been developed. This method allows production of large quantities of P. carinii organisms with very little contamination of host cells. A fivefold increase in the numbers of organisms was achieved, as determined by organism count, antigen detection, and DNA quantification. The majority of organisms produced by this method are trophozoites.

The nucleotide sequences of a portion of the large-subunit mitochondrial rRNA gene of Pneumocystis carinii derived from 12 patients were examined. Five sequences were found to be identical to the prototype sequence reported by Sinclair et al. (K. Sinclair, A. E. Wakefield, S. Banerji, and J. M. Hopkin, Mol. Biochem. Parasitol. 45:183-184, 1991). Six sequences differed from the prototype sequence at one to three positions. The remaining sequence was markedly different from the prototype sequence and appeared to be a hybrid of the human and rat P. carinii sequences. The results of this study indicate the existence of multiple P. carinii strains infecting humans and suggest that coinfections of animal and human P. carinii strains in the same host are possible.

Entactin (nidogen), a 150-kD sulfated glycoprotein, is a major component of basement membranes and forms a highly stable noncovalent complex with laminin. The complete amino acid sequence of mouse entactin has been derived from sequencing of cDNA clones. The 5.9-kb cDNA contains a 3,735-bp open reading frame followed by a 3'-untranslated region of 2.2 kb. The open reading frame encodes a 1,245-residue polypeptide with an unglycosylated Mr of 136,500, a 28-residue signal peptide, two Asn-linked glycosylation sites, and two potential Ca2+-binding sites. Analysis of the deduced amino acid sequence predicts that the molecule consists of two globular domains of 70 and 36 kD separated by a cysteine-rich domain of 28 kD. The COOH-terminal globular domain shows homology to the EGF precursor and the low density lipoprotein receptor. Entactin contains six EGF-type cysteine-rich repeat units and one copy of a cysteine-repeat motif found in thyroglobulin. The Arg-Gly-Asp cell recognition sequence is present in one of the EGF-type repeats, and a synthetic peptide from the putative cell-binding site of entactin was found to promote the attachment of mouse mammary tumor cells.

The purpose of this study was to compare the conventional radioimmunoassay (RIA) to an enzyme-linked immunoassay (EIA) for the measurement of Histoplasma antigen in banked urine specimens. A correlation between the two methods would allow the EIA to be used as a nonradioactive alternative to the established 125I RIA. The study used stored urine from patients diagnosed with histoplasmosis during an outbreak in Indianapolis which began in 1988. Control specimens from healthy adults, patients with other fungal infections, urinary tract infections, or nonfungal pneumonia were also tested. Both the RIA and EIA were run concurrently. The RIA system measured antigen levels of 0.4 to 27.0 RIA units, while the EIA measured antigen levels of 0.6 to 20.1 units. Both the EIA and RIA detected measurable antigen levels in urine from 50 of 56 patients (89%) with disseminated disease and 11 of 30 patients (37%) with self-limiting disease. One of 96 control specimens, from a patient with paracoccidioidomycosis, was positive with both systems. Antigen levels measured by EIA correlated well with those measured by the established RIA method (correlation coefficient, 0.974). The EIA is an acceptable alternative to the RIA for measuring Histoplasma antigen levels in urine specimens.

Sprague-Dawley rats treated for 8 weeks with cortisone acetate (25 mg per rat twice weekly) were immunosuppressed to variable degrees. A total of 55% lost over 12% of their initial body weight, had cortisol concentrations in serum more than five times greater than those of the controls, and had markedly depressed ratios of helper to non-helper T cells, in both the spleen and peripheral blood. Animals that gained weight during immunosuppression had cortisol concentrations in serum only three times higher than those of the controls, had normal ratios of helper to non-helper T cells in the spleen, and had only modestly reduced T-cell ratios in peripheral blood. The degree of Pneumocystis pneumonia was evaluated in impression smears and sections of lungs taken from immunosuppressed rats. Pneumocystis infections were more severe in the rats that showed the greatest weight loss. Weight change during immunosuppression may therefore be used as a reliable means for predicting the degree of Pneumocystis infection in living rats. This protocol allows the selection of uniformly infected rats for studies assessing drug therapy of Pneumocystis pneumonia.

Mouse embryonal carcinoma F9 cells were exposed to retinoic acid and dibutyryl cyclic AMP. The treated cells synthesized and secreted into the culture medium the basal lamina components, laminin (GP-1 and GP-2) and entactin. The time course of secretion of the basal lamina components was examined by electron microscopic and immunochemical procedures. The induction of the cells resulted in major morphological changes and the deposition of both laminin and entactin at the cell surface and cell junctions. Intracellular deposits of laminin could be localized to the endoplasmic reticulum and membrane-bound intracytoplasmic vacuoles. Concomitant with the appearance of laminin and entactin, there was a loss of fibronectin synthesis and a marked decrease in a 190,000-Da sulfated glycoprotein that appeared to be related to entactin. In the induced cells, laminin and entactin were associated in a complex that could be dissociated with low concentrations of sodium dodecyl sulfate. The induction of laminin and entactin seem to be independent. The enhanced synthesis of laminin appeared to be under transcriptional regulation since it was found that induced F9 cells contained translatable mRNA for GP-2 when tested in a rabbit reticulocyte lysate system. The uninduced cells did not contain detectable quantities of translatable GP-2 mRNA.

ABSTRACTThe sensitivity for detection of Histoplasmaantigen is lower in serum than in urine. In other antigen assays, treatment of serum at 104°C in the presence of EDTA was required for detection of antigenemia. Sensitivity and specificity for detection of Histoplasmaantigenemia were examined with or without EDTA heat treatment of the serum using the MVista Histoplasmaantigen enzyme immunoassay. A total of 94.6% of serum specimens from patients with AIDS and histoplasmosis that were negative untreated were positive after EDTA-heat treatment. Two-thirds of the negative serum specimens from patients with probable histoplasmosis, based upon clinical suspicion and Histoplasmaantigenuria, were positive after heat treatment. Specificity was 99.0% in controls, including healthy subjects and patients in whom histoplasmosis or blastomycosis, were excluded. Precision and reproducibility were good and excellent, respectively. These findings demonstrate improvement in sensitivity without reduction in specificity, precision, or reproducibility after heat-EDTA treatment.

The feasibility of predonated autologous blood transfusion and intraoperative blood salvage in elective abdominal aortic aneurysm repair was studied. Twenty consecutive patients were evaluated, of whom five were excluded according to protocol criteria. Patients each donated 1 unit blood 14 and 7 days before operation. A third unit was withdrawn in the anaesthetic room and replaced with Hartmann's solution, producing a haemodiluted state. Intraoperative losses were minimized using the Haemonetics Cell Saver III Plus autotransfusion system. Predonated blood from two patients passed its expiry date owing to repeated operation postponements, leaving 13 patients for study. The mean(s.d.) intraoperative blood loss was 700(300) ml with a mean(s.d.) intraoperative salvage of 420 (300) ml. Two patients were transfused with bank blood in breach of the protocol and two others were transfused according to clinical need. Thus nine patients safely avoided homologous transfusion. With autologous predonation, haemodilution and intraoperative blood salvage, elective aortic aneurysm repair can be performed safely with minimal need for homologous blood.

Rats free of latent Pneumocystis carinii organisms were immunosuppressed with adrenal corticosteroids and transtracheally injected with P. carinii. These animals subsequently developed P. carinii pneumonia. Infection was accomplished by using organisms from infected rat lung or from culture. Diffuse infection was produced with no significant differences in the numbers of organisms found in various lobes of the lungs. Infections progressed over time so that by 6 weeks postinoculation all animals were heavily infected. Infection by transtracheal injection has three advantages over current models. First, transtracheal injection provides a reliable model which is not dependent on naturally occurring latent Pneumocystis infection. Second, transtracheal injection allows the perpetuation of specific Pneumocystis strains. Third, transtracheal injection is a more rapid and economical means of producing severe Pneumocystis pneumonia.

The authors present the realisation of high-quality 1 m long continuously-written fibre Bragg gratings designed to compensate both second- and third-order fibre dispersion. These compact devices are ideal for counteracting the effects of fibre dispersion in high bit rate transmission systems.

Muscular dystrophy may be caused by disturbances in a number of muscle proteins that appear to be part of a chain of interacting molecules that includes cytoskeletal, cell membrane, and basement membrane components. We found that the skeletal muscle cells in two cases of Walker-Warburg syndrome were severely deficient in the laminin β2 chain and in adhalin. The findings indicate that these two proteins are key molecules in the interactive protein complex conferring muscle stability and cell survival.

No abstract available.

The authors demonstrate a highly practical and robust soliton transmission system with partial dispersion compensation. Error free transmission was obtained for 10 Gbit/s data over 1000 km of standard fibre with nominal dispersion of 17 ps/nm.km. Despite variations in the dispersion compensation ratio and the relatively high UV-induced birefringence of the fibre gratings, the system exhibits BERs < 10–10 for any state of input polarisation provided that the average intra-span dispersion is negative.

Two sources of rats free of latent Pneumocystis carinii are described. First, rats from a virus-free colony failed to develop infection after 8 weeks of immune suppression unless they were housed with previously infected rats. Second, pregnant rats (non-virus free) received trimethoprim-sulfamethoxazole from day 10 of gestation until the pups were weaned. Pups raised in filter-topped cages and immunosuppressed for 8 weeks were free of P. carinii infection.

CD40 ligand-CD40 ligation is important in the development of T-cell-mediated immune responses. The purpose of this study was to examine the role of CD40L in recovery from histoplasmosis using a murine model of intratracheally induced infection. B6C3F1 mice were infected intratracheally with Histoplasma capsulatum yeast and monitored for clearance of the organism from the lungs and spleen. CD40L treatment was begun on either day -2 or +2 post inoculation and continued until day 14 in CD4-depleted animals and from day -2 to day +4 in nonimmunosuppressed animals. Amphotericin B treatment was begun four days following inoculation and given every other day for 10 days. CD40L reduced fungal burden by less than one log when started two days before infection but did not act synergistically with low-dosage amphotericin B (0.2 mg kg-1 qod) in CD4 depleted mice. Low-dose amphotericin B, CD40L, and the combination of the two failed to lower the fungal burden in a second experiment using a more virulent isolate of the same strain of H. capsulatum in CD4-depleted mice. Furthermore, CD40L did not increase the concentrations of IFN-?, IL-12 or IL-10 in the lungs or spleens of infected animals. In summary, CD40L had minimal or no effect on the course of infection in this murine model of histoplasmosis.