Biomedical subjects
Publications and source records attributed to B S Chang.
Fibrous dysplasia of the rib is not uncommon, but is rarely demonstrated as a huge chest wall mass with severe clinical symptoms. A 59-year-old patient, presenting with a huge, rapidly expanding chest wall tumor compressing the lung, liver and heart accompanied by chest pain and dyspnea, is reported. The tumor was success-fully excised by local radical resection.
Previous investigations into the evolution of the Drosophila opsin gene family are extended by inter- and intraspecific DNA sequence comparisons of the Rh3 locus in the melanogaster subgroup and D. pseudoobscura. Two separate statistical tests of the neutral-mutation hypothesis suggest that random genetic drift is responsible for virtually all of the observed amino acid replacement substitutions within the melanogaster subgroup. Analyses incorporating the D. pseudoobscura sequences are enigmatic due to the accumulation of multiple substitutions, because the McDonald-Kreitman test is not applicable to species comparisons that approach mutational saturation. However, the data from D. pseudoobscura are not inconsistent with selective neutrality. The ratio of amino acid polymorphisms within species to fixed differences between species imply that there are approximately 31 possible neutral single-step amino-acid-replacement substitutions at this locus. Synonymous substitutions are unevenly distributed among the structural domains of the Rh3 gene. Patterns of synonymous polymorphism are analyzed with respect to GC content and codon bias, and are compared to other loci from the same species.
Light microscopic and immunohistochemical examination was undertaken of intracranial arteriovenous malformations (AVMs) surgically resected from 18 patients, each of whom had undergone preoperative angiographic embolization with multiple agents. Distinct patterns of tissue reaction to these agents were noted, even when more than one substance was present in a vascular lumen. Avitene produced the mildest tissue response but resulted in relatively early endothelialization and recanalization. Cyanoacrylates were longer-lasting but associated with more acute and chronic (including granulomatous) inflammation and vessel wall changes. Polyvinyl alcohol foam/ethanol mixture had intermediate properties. Endothelial proliferation over embolization material was confirmed using immunohistochemical application of an antibody to cell proliferation-specific proteins. The significance of these findings for combined endovascular and surgical treatment of cerebral vascular malformations is discussed.
Porcine pancreatic elastase, a well-characterized serine protease, has been used as a model to assess the effects of excessive humidity on solid-state stability of the lyophilized protein. Elastase lyophilized without excipients retained full activity immediately after freeze-drying but became denatured upon continued storage at 40 degrees C, 75% relative humidity. The extent of inactivation could be monitored through assays of amidolytic activity, as well as through changes in the circular dichroism (CD) and fluorescence spectra. Differential scanning calorimetry (DSC) was employed as a means of screening potential stabilizing additives; based on the results, sucrose and dextran 40 were selected for further evaluation. Both additives were effective in preventing denaturation. Possible mechanisms for the denaturation and stabilization of elastase are discussed.
We have reported previously that thyroid gland blood flow, expressed as vascular conductance (C) per mass, is decreased at very low and increased at very high chronic plasma TSH concentrations, but is apparently unchanged over a broad range of plasma TSH concentrations encompassing normal levels. The aim of the present study was to examine the apparently very steep dose-response relationship between elevated plasma TSH and thyroid vascular C/mass. In the first series of experiments, endogenous plasma TSH concentrations were manipulated by treating male Sprague-Dawley rats (250-280 g) for 6 days as follows: 1) controls (0.5 ml saline/day, ip), 2) propylthiouracil injections (2.0 mg PTU/day, ip), 3) PTU plus partial thyroid hormone replacement (2.0 mg PTU/day and 0.3-0.9 microgram T4 plus 0.075-0.225 microgram T3/100 g.day via continuous sc infusion), or 4) TRH (9-1200 micrograms TRH/100 g.day via continuous iv infusion). The vascular C values of the thyroid gland, salivary gland, kidney, and pancreas were determined using the reference sample version of the radioactive microsphere technique. PTU treatment led to the expected hypothyroidism, increased plasma TSH concentrations (959 +/- 66 vs. 154 +/- 22 ng/dl), increased thyroid weight (9.19 +/- 0.36 vs. 4.60 +/- 0.15 mg/100 g), and increased thyroid vascular C/mass (495 +/- 51 vs. 127 +/- 20 microliters/mm Hg.g/min). PTU-treated rats receiving partial thyroid hormone replacement demonstrated a dose-related suppression of plasma TSH, thyroid weight, and thyroid vascular C. Although, TRH treatments resulted in increased plasma TSH concentrations (e.g. 1200 micrograms TRH, 706 +/- 46 ng/dl) and thyroid weight (e.g. 1200 micrograms TRH, 7.45 +/- 0.41 mg/100 g), thyroid vascular C per tissue mass was not significantly increased after any TRH treatment (e.g. 1200 micrograms TRH, 166 +/- 19 microliters/mm Hg.g/min). Thus, at similarly elevated plasma TSH concentrations, the thyroid vascular C/mass of PTU- and TRH-treated rats constituted separate populations. Both PTU- and TRH-induced thyroid growth were accompanied by similar alterations in thyroid gland morphology (i.e. increased cellular mass with little change in the total amount of colloid). To investigate the mechanisms involved, groups of rats were treated for 6 days as follows: 1) control, 2) PTU or methimazole (25 mg MMI/day, ip), 3) PTU or MMI plus thyroid hormone replacement (1.2 micrograms T4 plus 0.3 microgram T3/d.100 g), 4) TRH (12 micrograms/100 g.day), and 5) PTU or MMI, thyroid hormones, and TRH.(ABSTRACT TRUNCATED AT 400 WORDS)
While primary and secondary malignant lymphomas have been well-documented in the CNS of patients with the acquired immunodeficiency syndrome (AIDS), only one case of lymphomatoid granulomatosis (LG) involving the CNS has been reported. We present three AIDS patients with multiple grossly evident foci of necrosis in the cerebral hemispheres which, on histologic evaluation, were seen to contain angiocentric mixed chronic inflammatory infiltrates with atypical mononuclear cells, luminal thrombosis, and infarction, which is typical of LG. LG was also identified in sections of the lung in one case. Lymphoma was found in other regions of the brain in two cases, suggesting the evolution of LG into cerebral lymphoma. In addition, widespread perivascular multinucleate syncytial giant cells, associated with human immunodeficiency virus (HIV) infection of the CNS, were identified in all patients. The features of LG, its relationship to lymphoma, and the possible etiologic role of an immunodeficiency state or the HIV virus in the pathogenesis of LG are discussed.
beta-Galactosidase from an autolytic strain of Streptococcus salivarius subsp. thermophilus was purified 109-fold to near homogeneity. The yield of purified enzyme was 41% and the specific activity was 592 o-nitrophenyl beta-D-galactopyranoside U/mg at 37 degrees C. Two isozymes were present, but only one subunit was detected, having a mol. wt of 116,000. Enzyme stability was 37-83 times greater in milk than in buffer in the range 60-65 degrees C. At 60 degrees C the half-life in milk was 146 min. Denaturation in buffer was first-order, but in milk the overall reaction order with respect to enzyme concentration was approximately 0.5. The activation energy for denaturation was 453 kJ/mol in milk and 372 kJ/mol in buffer. In milk the activation energy for lactose hydrolysis was 35.1 kJ/mol.
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The increased plasma bicarbonate concentration seen in hypercapnia implies that tubular bicarbonate reabsorption must be increased in the presence of an elevated Paco2. In contrast to early reports, more recent experimental data in acute hypercapnia have been interpreted to show that the observed increment in tubular reabsorption of bicarbonate factored for glomerular filtration rate (THCO3/GFR) is largely related to the concurrent changes in renal sodium reabsorption and to the increment in the filtered load of bicarbonate, and that acute hypercapnia per se causes little or no change in the tubular handling of bicarbonate. We reexamined this question by observing the changes in renal function occurring in the presence of a moderate elevation of plasma bicarbonate concentration in two groups of dogs. In group I, the elevation occurred as a result of acute hypercapnia during the administration of an "isometric" solution; in group II, it was caused by the infusion of identical amounts of an isotonic solution with the same concentration of sodium as in group I, but a higher bicarbonate concentration, in the presence of eucapnia. A subset of group II provided controls for the decrease in renal perfusion pressure that occurred spontaneously in group I. With increasing filtered loads of bicarbonate, fractional excretion (FE) of HCO3 increased in group II, whereas it dropped markedly in group I. Furthermore, the relative reabsorption rate of HCO3 compared with that of Cl (assessed by changes in fractional reabsorption (FR) of HCO3/Cl) decreased in group II, whereas it increased in group I. Although FENa also decreased in group II, the opposite changes in FR(HCO3/Cl) could not be attributed solely to concurrent changes in sodium handling, indicating that in the presence of acute hypercapnia there is a preferential reabsorption of bicarbonate that tends to perpetuate the increase in plasma bicarbonate concentration. By contrast, THCO3/GFR rose in both groups. The data are interpreted to reveal that acute hypercapnia, although causing a drop in renal perfusion pressure and in natriuresis, also has an additional specific effect on raising preferential bicarbonate reabsorption. This effect can be detected best by monitoring changes in the anionic composition of tubular reabsorbate, whereas it may not be unveiled by following changes in THCO3/GFR. Changes in THCO3/GFR may not yield useful information regarding the integrated response of the kidney to acid-base perturbations, and the conclusions of previous studies based on changes in this parameter must be carefully reexamined.
Dried smears of urinary sediment stained with Wright's stain were examined and compared in 20 selected patients with hematuria. In ten patients with microscopic hematuria and glomerular lesions demonstrated by renal biopsy, the urinary red cells were characteristically dysmorphic and hypochromic. This was distinctly different from the red cell morphology in ten patients with nonglomerular causes of hematuria, which was more like peripheral blood. The pathogenesis of the changes in red cell morphology seen in glomerular hematuria is unknown, but it appears not to be due to the urine composition per se. It is concluded that with some limitations, this simple, noninvasive technique may be useful in identifying a source of bleeding in the workup of hematuria.
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Quantitation of urinary protein excretion is used extensively for diagnostic and prognostic purposes and to assess the effects of therapy. The method most commonly used to measure urinary protein relies on 24-hour urine collections, which are time consuming, cumbersome, and often inaccurate. We reasoned that the urinary protein/creatinine ratio in a single voided urine sample should correlate well with the quantity of protein in timed urine collections. In a study of 46 specimens we found an excellent correlation between the protein content of a 24-hour urine collection and the protein/creatinine ratio in a single urine sample. The best correlation was found when samples were collected after the first voided morning specimen and before bedtime. We conclude that the determination of the protein/creatinine ratio in single urine samples obtained during normal daylight activity, when properly interpreted by taking into consideration the effect of different rates of creatinine excretion, can replace the 24-hour urine collection in the clinical quantitation of proteinuria. In the presence of stable renal function, a protein/creatinine ratio of more than 3.5 (mg/mg) can be taken to represent "nephrotic-range" proteinuria, and a ratio of less than 0.2 is within normal limits.
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Studies have demonstrated that the protective effect of secondary hypocapnia on plasma acidity during chronic HCl-acidosis is undermined by a renal-mediated decrement in plasma bicarbonate concentration induced by the hypocapnia itself. The present study was designed to assess whether the protection of "whole body" intracellular pH (pHi) is similarly undermined by this maladaptive response of the kidney. Whole body pHi was estimated by the 5,5 dimethyl-2,4-oxazolidinedione (DMO) method in seven unanesthetized dogs under each of three conditions: control, chronic HCl-acidosis (10 mEq H+/kg/day) with spontaneous secondary hypocapnia, and chronic HCl-acidosis with a normal level of carbon dioxide tension (maintained by the use of an environmental chamber). pHi was 6.71 +/- 0.02 during control, and 6.57 +/- 0.03 and 6.57 +/- 0.02 during the two acidosis periods, respectively. These results indicate that sustained secondary hypocapnia fails to render the intracellular compartment less acidic because of a maladaptive reduction in intracellular bicarbonate concentration.
The high mortality rate of patients afflicted with adult respiratory distress syndrome (ARDS) may be due, in part, to the hemodynamic changes and the barotrauma accompanying mechanical ventilation, especially when high positive pressure and oxygen tension are used. Recent experimental evidence suggests that prognosis may be improved by suspending ventilation: in the apneic condition, oxygenation can be maintained by transalveolar oxygen diffusion, while extracorporeal carbon dioxide removal (ECCO2R), achieved with membrane lungs, assures CO2 homeostasis. This technology, however, requires high blood flow rates, and is available only to very few specially equipped centers. We report results of experiments in dogs using an alternative approach to ECCO2R during apnea. Dissolved CO2 was converted to bicarbonate by the systemic infusion of NaOH at the rate of 0.15 mM/kg/min; the generated bicarbonate was then removed by hemodialysis against a bicarbonate-free dialysate, at a blood flow rate of 200 ml/min. Sodium and fluid balance were maintained by ultrafiltration. Observations in five dogs confirm that systemic pCO2, TCO2, and pH can be maintained well within physiologic ranges, and that prolonged apnea followed by full recovery can be achieved with this methodology. Because of the wide availability of dialysis equipment and expertise, and of lower extracorporeal blood flow requirements, ECCO2R by alkali administration and hemodialysis offers a potentially attractive alternative approach to the use of membrane lungs in the apneic therapy of ARDS.
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We performed detailed studies of renal function in two of five related patients with normal serum creatinine levels to determine the mechanism of their chronic azotemia. Inulin and para-amino-hippurate clearances, maximum tubular transport of para-aminohippurate, and renal acidification were within normal limits. In addition, renal concentrating and diluting abilities of these patients were similar to those of four normal controls. Urea clearances of both patients during maximum water diuresis (27.6 and 40.8 ml per minute per 1.73 m2) and antidiuresis (5.3 and 4.0), however, were much lower than mean (+/- S.E.M.) values in the normal controls (70.4 +/- 3.7 and 30.0 +/- 3.42 ml per minute per 1.73 m2, respectively). Thus decreased urea excretion despite otherwise normal renal function was responsible for the chronic azotemia of these patients. The genetic defect in renal urea clearance appeared to be inherited as an autosomal dominant trait.
A crossover, randomized, eight-week trial using eight adult volunteers was undertaken to (1) determine the efficacy of aluminum hydroxide in decreasing gastrointestinal phosphate absorption, (2) compare the effectiveness of "with meal" and "between meal" dosing schedules, and (3) compare the effectiveness of the capsule and liquid dosage forms. Four treatments, each with a daily dose of approximately 6 g, were taken on a three-times-a-day regimen. The effectiveness of the treatment regimens was measured by using two variables: the decrease in total urinary phosphorus excretion, and the increase in the percent tubular reabsorption of phosphorus (TRP). Aluminum hydroxide treatment produced a significant change in urinary phosphorus excretion (p less than 0.0005) and in percent TRP (p less than 0.0005). For the study population, total urinary phosphorus excretion was the determining factor in changing the percent TRP. The increase in TRP and the decrease in total urinary phosphorus excretion was of the same degree regardless of dosage form or dosage schedule. Aluminum hydroxide was effective in decreasing phosphorus absorption as measured in this study. It appears that aluminum hydroxide capsules could be used with equal efficacy as the liquid dosage form in controlling hyperphosphatemia in patients with chronic renal failure who will not comply with a treatment program using the liquid.