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Biomedical subjects

M Fernandes

Publications and source records attributed to M Fernandes.

At least 19 recordsLinked to original sources

HSF access to heat shock elements in vivo depends critically on promoter architecture defined by GAGA factor, TFIID, and RNA polymerase II binding sites.

Chromatin structure can modulate gene expression by limiting transcription factor access to gene promoters. We examined sequence elements of the Drosophila hsp70 promoter for their ability to facilitate the binding of the transcription factor, heat shock factor (HSF), to chromatin. We assayed HSF binding to various transgenic heat shock promoters in situ by measuring amounts of fluorescence at transgenic loci of polytene chromosomes that were stained with an HSF antibody. We found three promoter sequences that influence the access of HSF to its binding sites: the GAGA element, sequences surrounding the transcription start site, and a region in the leader of hsp70 where RNA polymerase II arrests during early elongation. The GAGA element has been shown previously to disrupt nucleosome structure. Because the two other critical regions include sequences that are required for stable binding of TFIID in vitro, we examined the in vivo occupancy of the TATA elements in the transgenic promoters. We found that TATA occupancy correlated with HSF binding for some promoters. However, in all cases HSF accessibility correlated with the presence of paused RNA polymerase II. We propose that a complex promoter architecture is established by multiple interdependent factors, including GAGA factor, TFIID, and RNA polymerase II, and that this structure is critical for HSF binding in vivo.

Animals

Gas-forming infections in genitourinary tract.

Diabetes mellitus associated with urinary tract infections and ureteral obstruction can be predisposing factors leading to emphysematous pyelonephritis. Fever, flank pains, and a palpable renal mass, associated with dehydration and hyperglycemia, were the most frequent presenting symptoms associated with emphysematous pyelonephritis. Computerized tomography (CT) scan is the best method to identify a renal or perirenal abscess and its ramifications. Intravenous antibiotic therapy is determined by blood and urine cultures. Mortality was zero in patients treated by nephrectomy. One patient who had incision and drainage of a renal abscess died of sepsis, and 1 patient died of sepsis following incision and drainage of a prostatic abscess. Patients with cystitis emphysematosa require antibiotic therapy and relief of bladder outlet obstruction. Prostatic abscess is best treated by perineal incision and drainage. Periurethral scrotal abscesses should be incised, drained, and the overlying necrotic skin debrided. Early diagnosis and aggressive medical and surgical management of gas-forming infections of the genitourinary tract are vital.

Abscess

A new Tay-Sachs disease B1 allele in exon 7 in two compound heterozygotes each with a second novel mutation.

Three novel Tay--Sachs Disease (TSD) mutations have been identified in two unrelated, non-Jewish compound heterozygous patients. A G772C transversion mutation causing an Asp258His substitution is shared by both patients. The mutant enzyme had been characterized, on the basis of previous kinetic studies (1) as a B1, or alpha-subunit active site mutation. This is the first B1 mutation not found in codon 178 (exon 5). A C508T transition causing an Arg170Trp substitution also occurred in one of the patients. The third mutation is a two base deletion occurring in exon 8 involving the loss of either nts 927-928 or 929-930 in codon 310. The deletion creates an inframe termination codon 35 bases downstream. The Arg170Trp mutation was also detected in a third unrelated TSD patient. In both families this allele was traced to French Canadian ancestors originating in the Estrie region of the province of Quebec. This mutation is the third TSD allele unique to the French Canadian population and the ancestral origins of the carrier parents are distant from the center of diffusion of the more common 7.6 kb deletion mutation which is in the eastern part of the province.

Alleles

Effects of beta blockade on systolic and diastolic left ventricular function at rest and during exercise in patients with chronic stable angina pectoris.

This study examined the effects of beta blockade with betaxolol, a cardioselective, lipid-soluble, beta-adrenergic-blocking agent, on rest and exercise systolic and diastolic left ventricular function in 15 patients, aged 40 to 70 years (mean = 52), with chronic stable angina pectoris. Each patient underwent three upright exercise studies at identical workloads; the first was a baseline study, the second was done 3 hours after a single oral dose, and the third was obtained after chronic therapy for 2 weeks. Beta blockade was evident by significant decreases in heart rate, systolic blood pressure, and diastolic blood pressure at rest and during exercise (p less than 0.04). Although there were no significant changes (at rest or during exercise) in mean left ventricular ejection fraction and peak filling rate, individual variations were seen after 3 hours and 2 weeks of therapy. During chronic therapy, the peak filling rate increased in three patients, decreased in five, and remained unchanged in seven. Also, discordant changes in systolic and diastolic functions were seen at rest and during exercise during both acute and chronic therapy. Thus, although acute and chronic beta blockade produces no significant changes in mean measurements of diastolic and systolic left ventricular performance, individual variations and discordant results are seen in many patients. The acute effects are generally consistent with the chronic effects, but exceptions are present.

Adrenergic beta-Antagonists

Bilateral renal oncocytoma: report of 2 cases and review of literature.

We report 2 cases of synchronous bilateral renal oncocytoma treated by radical nephrectomy on 1 side and by partial nephrectomy on the other side. Long-term followup serves to confirm the noninvasive nature of this disease. We recommend conservative management based upon radiological and gross pathological findings.

Adenoma

Comparison of subclavian vein with femoral vein catheterization for hemodialysis.

Subclavian vein catheterization (SVC) is not widely accepted for vascular access because it is considered more invasive than femoral vein catheterization (FVC). The use of FVC and SVC for acute vascular access was compared for 9 mo each. Complications were minimal with both, but access related hospitalizations were lower and the number of out-patient dialyses performed were higher with SVC than FVC. Complications with SVC might have been minimized by using an 18-gauge metallic needle for insertion, avoiding interdialytic infusions and using SVC for less than 4 wk.

Catheterization

Increment in dialysate sodium with sodium chloride or bicarbonate addition.

Hemodialysis was performed in 12 patients for 2 weeks each utilizing acetate dialysate containing 134 mEq/L sodium and dialysate containing 143 mEq/L sodium, achieved by the addition of sodium chloride or sodium bicarbonate to the acetate dialysate. Intradialytic morbidity was lower, dialysis hypoxemia less marked, and predialysis blood pH higher with the bicarbonate-than with the chloride-added dialysate. The long-term use of sodium bicarbonate-added dialysate in three patients was safe. Dialysate pH adjustment was not required. These findings suggest that the addition of sodium bicarbonate (50-75 g) to acetate dialysate may be preferred to sodium chloride for increasing dialysate sodium in selected patients.

Aged

Frequency resolution and discrimination of constant and dynamic tones in normal and hearing-impaired listeners.

Frequency resolution and three tasks of frequency discrimination were measured at 500 and 4000 Hz in 12 normal and 12 hearing-impaired listeners. A three-interval, two-alternative forced-choice procedure was used. Frequency resolution was measured with an abbreviated psychoacoustical tuning curve. Frequency discrimination was measured for (1) a fixed-frequency standard and target, (2) a fixed-frequency standard and a frequency-transition target, and (3) frequency-transition standard and a frequency-transition target. The 50-ms frequency transitions had the same final frequency as the standards, but the initial frequency was lowered to obtain about 79% discrimination performance. There was a strong relationship between poor frequency resolution and elevated pure-tone thresholds, but only a very weak relationship between poor frequency discrimination and elevated pure-tone thresholds. Several hearing-impaired listeners had normal discrimination performance together with pure-tone thresholds of 80-90 dB HL. A slight correlation was found between word recognition and frequency discrimination, but a detailed comparison of the phonetic errors and either the frequency-discrimination or frequency-resolution tasks failed to suggest any consistent interdependencies. These results are consistent with previous work that has suggested that frequency resolution and frequency discrimination are independent processes.

Acoustic Stimulation

The form and structure of supernumerary hindlimbs formed following skin grafting and nerve deviation in the newt Triturus cristatus.

The results of a series of skin grafting experiments performed on the hindlimb of the newt Triturus cristatus are described. In an attempt to limit the position of origin and the complexity of supernumerary limb outgrowths four experimental features were varied. These were 1) size of skin grafts; 2) their position of origin; 3) the position to which they were grafted; and 4) the presence or absence of nerves of two different sizes at the graft site. The degree of distal outgrowth and the pattern of the supernumerary structures in the anterior to posterior and dorsal to ventral axes were assessed. The results are discussed in terms of the control of pattern regulation in localized populations of limb blastema cells.

Animals

Development and loss of tolerance to morphine in the rat.

The development of a differential tolerance to morphine was investigated with respect to the mean effective dose, the threshold dose of tolerance, the degree of tolerance after a fixed dose, and the speed of tolerance loss. The mean effective doses, the threshold doses of tolerance, and the degree of tolerance differed considerably from effect to effect, whereas in all tests tolerance loss remained the same. The mean effective doses were not correlated to threshold doses of tolerance, degree of tolerance, or to the loss of tolerance, but a strong correlation exists between threshold doses of tolerance and degree of tolerance to all effects measured. Consequences of these results upon current theories of tolerance are discussed.

Animals

Frequency resolution and hearing loss.

Future scientific and diagnostic interest in frequency resolution requires an evaluation of the different methods that are available to measure it. We compared three methods: (1) pure-tone thresholds in broadband noise, (2) pure-tone thresholds in the presence of a fixed pure-tone masker and (3) psychoacoustical tuning curves. We additionally obtained estimates of temporal integration and of speech intelligibility in noise. Three subject groups were tested: 10 normals, 13 subjects with a noise-induced hearing loss and 18 subjects with a cochlear hearing loss but no history of noise exposure. Generally the three measures of frequency resolution show moderate agreement with each other. Poor frequency resolution is invariably associated with a pure-tone threshold loss. Temporal integration appears unrelated either to the pure-tone threshold loss or frequency resolution. Some of the measures of frequency resolution display significant correlation with speech intelligibility in noise. However, since both variables are correlated with pure-tone threshold loss the exact relationship between frequency resolution and speech intelligibility cannot be clearly established.

Adolescent

Body fluid volumes in the spontaneously hypertensive rat.

1. Plasma volume, packed cell volume (PCV), blood pressure, extracellular fluid volume (ECFV) and evans blue disappearance rate were measured in conscious spontaneously hypertensive rats and in weight-matched Wistar normotensive rats. 2. Over the weight range studied (250-350 g), plasma and blood volumes were significantly lower in the spontaneously hypertensive rat. Extracellular fluid volumes were similar in the two groups. PCV and Evans blue disappearance rates were significantly higher in the spontaneously hypertensive rat. 3. Negative correlations were obtained between plasma volume and mean arterial pressure and between the plasma/interstitial fluid volume ratio and mean arterial pressure. 4. The normal extracellular fluid volume and the lack of correlation with mean arterial pressure excludes volume expansion as a pressor mechanism during the established phase of hypertension in the spontaneously hypertensive rat.

Animals