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J Nowakowski

Publications and source records attributed to J Nowakowski.

At least 55 records · Page 3Linked to original sources
PubMed1996

Promotion of synthetic amyloid beta-peptide fibrillization by cell culture media and cessation of fibrillization by serum.

Dulbecco's modified Eagle's medium promotes aggregation and fibrillization of the synthetic amyloid beta 1-40 and beta 1-42 peptides more than RPMI and OPTI media. Fibrillization in all of these media is faster than in phosphate-buffered saline and Tris buffer. Normal and heat-inactivated fetal bovine and human serum abolish amyloid fibril formation in buffers and cell culture media. Fibrillar amyloid formed during 2-day-long incubation in cell culture media and buffers is defibrillized by 1-day-long treatment with human and bovine serum. This study indicates that amyloid beta fibrillogenesis in cell culture should be studied in serum-free media or in media with a low concentration of serum.

Amyloid beta-Protein Precursor↗
PubMed1996

Conformation of an RNA molecule that models the P4/P6 junction for group I introns.

We present a three-dimensional structure of a 34-nucleotide RNA molecule determined by NMR spectroscopy. The molecule was designed to form a junction between two double-helical stems whose sequence was based on the P4/P6 domain from group I introns. There are 5' and 3' single-strand overhangs at the junctions of the stems. Contrary to our expectations, we found that the 3' end of the molecule is placed in the minor and not the major groove of the P4 helix. As a result of tertiary contacts and stacking interactions from nucleotides in the 3' end, the junction helices are rotated in a left-handed fashion and do not stack coaxially. This conformation is highly dependent on the presence of single-stranded nucleotides at the 3' overhang. When the 3' end is removed, the molecule assumes a radically different structure with 5' end in the minor groove of the P6 helix and overall right-handed rotation between the stems. Only one nucleotide at the 3' end is sufficient to change the geometry of the junction.

Base Sequence↗
PubMed1996

Liver function in early Lyme disease.

To evaluate the frequency, pattern, and severity of liver function test abnormalities in patients with Lyme disease associated with erythema migrans (EM), 115 individuals with no other identifiable cause for liver function test abnormalities who presented with EM between July 1990 and September 1993 were prospectively evaluated. For individuals with abnormal liver function tests, common causes of hepatitis, including hepatitis A, B, and C, were excluded. A local control group was used for comparison. Forty-six (40%) patients had at least one liver test abnormality, and 31 (27%) had more than 1 abnormality compared with 19 (19%) and 4 (4%) of controls, respectively (P < .01 for each comparison). gamma-Glutamyl transpeptidase (28%) and alanine transaminase (ALT) (27%) were the most frequently elevated liver function tests among Lyme disease patients. Anorexia, nausea, or vomiting was reported by 30% of patients, but did not occur more frequently in patients with elevated liver function tests compared with those with normal values. Patients with early disseminated Lyme disease were more likely to have elevated liver function studies (66%) compared with patients with localized disease (34%) (P = .002). After antibiotic treatment, elevated liver function tests improved or resolved in most patients. Liver function test abnormalities are common in patients with EM but were mild, most often not associated with symptoms, and improved or resolved by 3 weeks after the onset of antibiotic therapy in most patients.

Adult↗
PubMed1996

Efficacy of antibiotic prophylaxis for prevention of Lyme disease.

OBJECTIVE: To determine if antibiotic prophylaxis following a dear tick bite is effective in reducing the risk of developing Lyme disease. DESIGN: Meta-analysis of published trials. DATA IDENTIFICATION: Clinical trials were identified by a computerised literature search of MEDLINE and by an assessment of the bibliographies of published studies. STUDY SELECTION: Trials were included in the analysis if their patients were randomly allocated to a treatment or control group, enrolled within 72 hours following an Ixodes tick bite, and had no clinical evidence of Lyme disease at enrollment. Three trials were selected for review after inclusion criteria were applied. DATA EXTRACTION: Data were extracted for details of study design, patient characteristics, interventions, duration of therapy, and number of adverse events in each arm of therapy. RESULTS OF DATA SYNTHESIS: Among the 600 patients with Ixodes tick bites, the rate of infection in the placebo group was 1.4%. In contrast, patients who received antibiotic prophylaxis had a 0% infection rate. The pooled odds ratio, comparing prophylaxis to placebo, was 0.0 (95% confidence interval 0.0, 1.5) (p = .12). CONCLUSIONS: The available evidence to date suggests that the routine use of antibiotic prophylaxis for the prevention of Lyme disease remains uncertain. Meta-analysis of the controlled trials failed to establish definitive treatment efficacy owing to the small sample size of the combined trials and the low rates of infection following a deer tick bite. A larger randomized trial is needed to demonstrate definitively that prophylaxis is more effective than placebo in reducing the risk of early Lyme disease in endemic areas.

Amoxicillin↗
PubMed1996

The clinical spectrum of early Lyme borreliosis in patients with culture-confirmed erythema migrans.

BACKGROUND: The diagnosis of erythema migrans (EM), the characteristic rash of early Lyme borreliosis, is based primarily on its clinical appearance since it often occurs prior to the development of a specific antibody response. Other skin disorders, however, may be confused with EM. METHODS: Between June 1991 and September 1993, a prospective study was conducted at the Lyme Disease Diagnostic Center of the Westchester County Medical Center to isolate Borrelia burgdorferi systematically from patients with Em, and to characterize the clinical manifestations of patients with culture-documented infection. Skin biopsies and/or needle aspirates of the advancing margin of primary lesions, and blood specimens from adult patients were cultured for B burgdorferi in modified Barbour-Stoenner-Kelly medium at 33 degrees C. RESULTS: B burgdorferi was recovered from 79 patients (49 [62%] males) ranging in age from 16 to 76 years old (mean, 43 +/- 14 years old). Maximum EM diameter (mean, 16 +/- 10 cm; range, 6-73 cm) was a function of EM duration (mean 6.7 +/- 6.4 days; range, 1-39 days) (correlation coefficient = 0.7; P < 0.001). Twenty (25%) patients had noted a tick bite at the site of the primary lesion a mean of 10 days (range, 1-27 days) before onset. Multiple EM lesions (range, 2-70) were present in 14 (18%) patients. Systemic symptoms were present at the time of culture in 54 patients (68%) including fatigue (54%), arthralgia (44%), myalgia (44%), headache, (42%), fever and/or chills (39%), stiff neck (35%), and anorexia (26%). Thirty-three patients (42%) had at least one objective finding on physical examination in addition to EM, including 18 (23%) with localized lymphadenopathy, 13 (16%) with fever (t > or = 37.8 degrees C), seven (9%) with tender neck flexion, six (8%) with joint tenderness, and 1 each with joint swelling, nuchal rigidity, and facial nerve palsy. No patient had new electrocardiogram evidence of atrioventricular block. Liver function assays were abnormally elevated in 37% of patients. Thirty-four percent of patients were seropositive by enzyme-linked immunosorbent assay at presentation. Most others rapidly seroconverted so that 69 of 78 evaluable patients (88%) were seropositive at some point during the first month after diagnosis. CONCLUSIONS: We describe the largest group of culture-positive patients with EM from the United States to date. Although systemic symptoms were present in most patients, objective evidence of advanced disease was uncommon. Our patients with culture-confirmed EM were less sick than those described in the days before culture confirmation was possible. The ability to isolate B burgdorferi from lesional skin of large numbers of patients with EM should make culture-positive patients the standard by which to define manifestations of early Lyme borreliosis associated with this rash. Microbiologic documentation of Lyme borreliosis will help delineate the manifestations of this illness, and should form the framework for research directed at pathophysiology, diagnosis, treatment, and prevention.

Adolescent↗
PubMed1996

Evolution of the serologic response to Borrelia burgdorferi in treated patients with culture-confirmed erythema migrans.

We investigated the appearance and evolution of immunoglobulin M (IgM) and IgG antibodies to Borrelia burgdorferi in 46 patients with culture-proven erythema migrans (EM). All patients received antimicrobial treatment and were prospectively evaluated for up to 1 year. A total of 257 serially collected serum samples were tested by commercial IgG-IgM enzyme-linked immunosorbent assay and separate IgM and IgG immunoblots (IBs). At the baseline, 33% of the patients had a positive ELISA result and 43% of the patients had a positive IgM IB result by using the criteria of the Centers for Disease Control and Prevention-Association of State and Territorial Public Health Laboratory Directors for the interpretation of IB results. Positive serology at the baseline and the rate of seroconversion correlated directly with disease duration and/or evidence of dissemination prior to treatment. At days 8 to 14 after the baseline, 91% of patients had a positive ELISA result and/or IgM IB result. Peak IgM antibody levels were seen at this time in patients with localized or disseminated disease. The most frequent IgM bands at the baseline and the peak were of 24 kDa (OspC), 41 kDa, and 37 kDa. Although 89% of the patients developed IgG antibodies as determined at a follow-up examination, only 22% were positive by the IgG IB criteria of the Centers for Disease Control and Prevention-Association of State and Territorial Public Health Laboratory Directors. The persistence of antibodies was directly related to disease duration and/or dissemination prior to treatment. Since IgM antibodies to the 24- and 41-kDa antigens remained detectable for long periods, 38% of IgM IBs were still positive at 1 year postbaseline. IgM to antigens of 39, 58, 60, 66, or 93 kDa, conversely, were most often seen in sera obtained within 1 month postbaseline. Their presence may be of assistance in confirming a recent infection with B. burgdorferi in individuals living in areas where Lyme disease is endemic.

Antibodies, Bacterial↗
PubMed1996

Molecular typing of Borrelia burgdorferi from Lyme disease patients by PCR-restriction fragment length polymorphism analysis.

Ninety-three Borrelia burgdorferi isolates obtained from erythema migrans lesions or blood of Lyme disease patients in Westchester County, N.Y., between 1991 and 1994 were characterized by PCR-restriction fragment length polymorphism (PCR-RFLP) analysis of the 16S-23S rRNA gene spacer. All isolates could be classified into three distinct RFLP types. Among the 82 skin biopsy isolates studied, 21 (25.6%) were type 1, 37 (45.1%) were type 2, and 21 (25.6%) were type 3. Three (3.7%) cultures contained a mixture of two isolates with distinct RFLP types. The 11 isolates cultured from blood showed a similar predominance of RFLP type 2 (6 of 11; 54.5%) relative to types 1 (2 of 11; 18.2%) and 3 (3 of 11; 27.3%). For one patient both skin and blood isolates were cultured, and RFLP analysis revealed that these isolates differed from one another. This study demonstrates that there is genotypic heterogeneity in B. burgdorferi strains infecting Lyme disease patients, and this typing approach may allow differentiation of isolates with various degrees of pathogenic potential.

Bacterial Typing Techniques↗
PubMed1995

The origin of amyloid in cerebral vessels of aged dogs.

Our morphometric study of 30 dogs, mongrels, from 6.5 to 26.5 years of age, shows amyloid angiopathy in cortical and leptomeningeal vessels of all dogs older than 13.2 years of age, and the increase in the numerical density of amyloid-positive vessels correlated with age. Cluster analysis distinguished the group of six dogs (25%) to be relatively less affected, a large group of 13 animals (54%) to have moderate pathology, and five dogs (21%) to have severe amyloid angiopathy. Amyloid accumulation starts in large vessels, particularly in the tunica media of large arteries. Amyloid deposition appears to be associated with smooth muscle cells. Ultrastructural studies of samples from nine dogs are in agreement with in vitro studies suggesting that smooth muscle cells are the source of soluble amyloid beta. beta-protein polymerizes in the basal lamina of the tunica media. Muscle cells in the area of amyloid-beta accumulation degenerate and die. Thioflavin-positivity of only 24% of cortical and 66% of leptomeningeal beta-protein-positive vessels suggests that thioflavin-negative deposits contain soluble, not yet fibrillized protein and/or partially degraded and depolymerized amyloid.

Aging↗
PubMed1995

Doxycycline versus tetracycline therapy for Lyme disease associated with erythema migrans.

BACKGROUND: Doxycycline is widely used to treat Lyme disease associated with erythema migrans. Whether it is comparable to tetracycline is unknown. OBJECTIVE: We conducted a two-part retrospective analysis of (1) the safety and efficacy of doxycycline compared with tetracycline and (2) the safety and efficacy of a 14-day versus a 20-day course of doxycycline. METHODS: Twenty-seven patients given tetracycline (500 mg four times a day for 14 days [group 1]) were compared retrospectively with 21 patients who received doxycycline (100 mg two or three times a day for 14 days [group 2]). The results for group 2 were also compared with that of 38 patients who received doxycycline for 20 days (100 mg three times daily) in a prospective treatment trial (group 3). RESULTS: There was no significant difference in the incidence of adverse drug effects or in efficacy at 1 month, but at 1 year there was a trend toward a better outcome in the group treated with tetracycline (p = 0.08). A 14-day course of doxycycline was comparable to a 20-day course in the incidence of adverse drug effects and in clinical outcome. CONCLUSION: The principal advantage of doxycycline over tetracycline for the treatment of Lyme disease associated with erythema migrans is the convenience of less frequent dosing, not enhanced efficacy or safety. There appears to be no advantage in extending treatment with doxycycline from 14 to 20 days.

Administration, Oral↗
PubMed1993

Failure to isolate Borrelia burgdorferi after antimicrobial therapy in culture-documented Lyme borreliosis associated with erythema migrans: report of a prospective study.

BACKGROUND: Borrelia burgdorferi, the etiologic agent of Lyme borreliosis, has occasionally been isolated from tissues or body fluids of patients after antimicrobial treatment. A prospective study of patients with Lyme borreliosis associated with erythema migrans (EM) was initiated in Westchester County, New York, to determine: (1) the clinical and laboratory parameters associated with culture positivity, and (2) the microbiologic response to treatment. METHODS: Skin biopsies were performed in patients with EM and cultured for B. burgdorferi in modified Barbour-Stoenner-Kelly medium at 33 degrees C. Subsequent biopsies for culture were performed adjacent to the original biopsy site for culture-positive patients after the completion of antimicrobial therapy. RESULTS: Initial biopsy cultures were performed for 44 patients; 6 were unevaluable due to culture contamination with other bacteria. Cultures were positive in 21 of 29 patients prior to treatment (72%), but in none of 9 patients during treatment (p < 0.001). The only other identified factor associated with successful recovery of B. burgdorferi was shorter duration of EM. When patients who had received prior antimicrobial therapy were excluded, the mean duration of the EM lesion for those with positive cultures was 5.0 +/- 5.2 days compared with 14.6 +/- 9.9 days for those with negative cultures (p < 0.01). B. burgdorferi could not be reisolated from any of 18 evaluable subsequent biopsies of skin from 13 culture-positive patients 4 to 209 days after completion of a course of antimicrobial therapy. Five patients had negative subsequent biopsy cultures on two separate occasions 3 to 5 months apart. CONCLUSIONS: After brief courses of antibiotics, B. burgdorferi appears to be rapidly eliminated from the skin at EM sites. The ability to recover B. burgdorferi from skin biopsy cultures of untreated patients with EM lesions wanes with increasing duration of EM, suggesting that this organism may also be spontaneously cleared from skin over time.

Adult↗
PubMed1993

Serodiagnosis in early Lyme disease.

Using a commercially available enzyme-linked immunosorbent assay (ELISA) and an immunoblot assay (IB), we tested sera from 100 patients with erythema migrans (EM) seen in 1991 a the Westchester County Medical Center Lyme Disease Diagnostic Center. Convalescent-phase sera were available from 59 patients. Fifty-five patients had EM of < 7 days' duration, 31 had EM of 7 to 14 days' duration, and 14 had EM of > 14 days' duration. During the acute phase of infection, 35 patients had a positive ELISA result and 43 had a positive IB result by the recently published criteria of Dressler et al. (F. Dressler, J. A. Whalen, B. N. Reinhardt, and A. C. Steere, J. Infect. Dis. 167:392-400, 1993) for interpretation of IB in patients with Lyme disease. A greater sensitivity of IB was observed in patients with EM of < 7 days' duration, as follows: 14 of 55 (25%) for IB versus 7 of 55 (13%) for ELISA (P = 0.144). Sera of all 14 patients with EM of > 14 days' duration were reactive by both tests, as follows: 13 positive and 1 equivocal by ELISA and 12 positive and 2 indeterminate by the IB. The band reactivity most frequently observed in the IB was to the 41- and 25-kDa antigens, the latter being the most frequent band observed in immunoglobulin M blots. Seroconversion was observed in 74 and 64% of evaluable patients by ELISA and IB, respectively, despite the use of antibiotic therapy.

Adult↗
PubMed1992

Use of a novel technique of cutaneous lavage for diagnosis of Lyme disease associated with erythema migrans.

OBJECTIVE: Determining the microbial cause of cellulitis is often difficult. In this study, a novel two-needle lavage technique was used to culture Borrelia burgdorferi from the skin of suspected erythema migrans lesions. DESIGN: The yield of lavage cultures for B burgdorferi was compared with that of a 2-mm skin biopsy sample. SETTING: A Lyme disease diagnostic center located in an area in which Lyme disease is epidemic. PATIENTS: Forty-five patients with suspected erythema migrans who had not been treated with antimicrobial agents. INTERVENTION: Cutaneous lavage of the advancing edge of a suspected primary erythema migrans lesion was done for all 45 participants, 33 of whom also had a skin biopsy of the same lesion at an identical (14) or an adjacent (19) site. MAIN OUTCOME MEASURES: Growth of B burgdorferi in in vitro culture. RESULTS: Lavage fluid cultures grew B burgdorferi in 13 (29%) of the 45 cases (95% confidence interval [CI], 16% to 44%). Among the 33 cases in which both lavage and skin biopsy cultures were done, the yield of lavage culture was less than that of biopsy culture (P less than .09, 12/33 vs 20/33). If contaminated cultures are excluded, this difference is significant (P less than .05, 12/30 vs 20/27). CONCLUSION: Cutaneous lavage is a new diagnostic technique for recovery of B burgdorferi from erythema migrans lesions that has potential applicability to other types of cutaneous infections.

Biopsy↗
PubMed1992

[Alcohol decreases the alpha subunit, LH and testosterone secretion in response to LH-RH].

UNLABELLED: In our previous study we showed that alcohol disturbed the circadian rhythms of LH, testosterone and its conversion to DHT. To determine the effect of LH-RH on pituitary-gonadal function before and after alcohol, 11 male volunteers aged 24-29 years (mean 25.5) were investigated. Blood for hormonal estimations was withdrawn before and 20, 30, 60, and 120 min after LH-RH. In every case, the LH-RH test was performed twice: 6 hours after placebo and, a week later, 6 hours after alcohol administered orally, in dose of 1.0 g/kg bw. The LH, FSH, alpha-subunit and testosterone concentrations were measured with radioimmunological methods. RESULTS: It was shown that alcohol significantly inhibited LH (p < 0.05), alpha-subunit (p < 0.02) and testosterone (p < 0.001) response to LH-RH stimulation, but not that of FSH.

Adult↗
PubMed1992

The effect of oral ethanol ingestion on the diurnal neurotensin secretion in man.

Neurotensin is a tridecapeptide, present in the central nervous system and the gastrointestinal tract in man and animals. The affect of orally administered ethanol (1 g/kg body weight) on the neurotensin secretion over 24 hr period was studied in eight young healthy men. No significant circadian rhythm of neurotensin secretion was detected in the eight subjects studied. Ethanol produced a progressive rise in the plasma level of neurotensin reaching a maximum at 12:00 (13.8 +/- 8.6 pmol/l). At 12:00 and 14:00, the neurotensin concentrations were significantly higher than on the placebo day (p < 0.05). The secretion rate of neurotensin was determined approximately using the area under the curve method. Ethanol produced a transient rise in neurotensin secretion over the first 12 hrs period (08:00-20:00 h) after its administration (p < 0.02). The observation that ethanol increases transiently the neurotensin secretion in man supports the hypothesis that neurotensin may be involved in the biological effect of ethanol. The source of its secretion remains to be elucidated.

Adult↗
PubMed1987

The role of opiate, dopaminergic, and adrenergic systems in the hypothalamo-pituitary dysfunction in obesity.

UNLABELLED: In order to evaluate the role of opiate, dopaminergic and adrenergic systems in the mechanism of hypothalamo-pituitary disturbances in obesity, 9 obese women and 14 healthy women were investigated. Serum GH, LH, beta-endorphin and cortisol concentrations were measured after administration of clonidine, an alpha 2-adrenergic receptor agonist, and naloxone, an opiate antagonist. Additionally, PRL levels were measured after administration of the dopamine receptor blocker metoclopramide. An impaired GH response to clonidine and naloxone was found in obese women. However, a marked increase in beta-endorphin was observed in obese patients after clonidine administration. Naloxone did not cause any significant change in beta-endorphin release. Neither clonidine nor naloxone induced any change in LH release. Serum PRL concentrations in response to metoclopramide were significantly higher in obese patients than in healthy women. IN CONCLUSION: Disturbed activity in opiate, adrenergic, and dopaminergic systems may be of pathogenetic importance in a hypothalamo-pituitary dysfunction in obesity. The occurrence of hypothalamic amenorrhoea as well as the presence of abnormalities of the central nervous system regulation of GH, PRL, ACTH, cortisol, insulin and vasopressin output might point to a generalized hypothalamo-pituitary dysfunction in obesity.

Adolescent↗