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Biomedical subjects

J J Huang

Publications and source records attributed to J J Huang.

At least 19 recordsLinked to original sources

Acute bacterial nephritis: a clinicoradiologic correlation based on computed tomography.

PURPOSE: Acute bacterial nephritis (ABN) represents localized, nonliquefied renal infection, and the subsequent alteration of tissue densities can be readily detected by computed tomography (CT). In recent literature, a variety of renal parenchymal alterations observed on CT were reported. However, previous reports on the clinical course of ABN were inconsistent and lacked correlation with radiologic findings. In this investigation, we attempt to correlate the severity of clinical manifestations with CT findings in ABN and draw some conclusions regarding the natural history, pathophysiology, and clinical management of this disease. PATIENTS AND METHODS: From July 1988 to June 1991, 30 cases of ABN were evaluated at our institute. On the basis of postcontrast-enhanced CT findings, 28 cases were grouped into (1) Group I (7 cases), wedge-shaped lesions (focal or diffuse); (2) Group II (12 cases), focal mass-like lesions; and (3) Group III (9 cases), diffuse (multifocal) mass-like lesions. The clinical features and outcomes of the three groups were compared. The positive detecting rates and clinical usefulness of ultrasonographic (US) and urographic examinations were also studied in each group. RESULTS: An excellent correlation can be demonstrated between the clinical parameters (including underlying diseases, maximum temperature and leukocyte count, duration of fever, flank pain, leukocytosis, and pyuria; the incidence of septic shock, diabetic ketoacidosis, and acute renal failure; and outcome) and the pattern of renal parenchymal abnormalities detected on CT. The clinical features in Group I patients displayed many similarities with those in uncomplicated acute pyelonephritis (APN) reported previously, and responded to antibiotic therapy promptly. Most patients in Group II were successfully treated with antibiotics but had a protracted clinical course with a slower clinical improvement than Group I. Only one case with a Group II lesion was noted to progress to renal abscess formation and extrarenal involvement. In comparison, 33% of the patients in Group III died despite antibiotic therapy. Our data also show that US examination is sensitive in detecting Group II ABN lesions (62% positive rate), and revealed marked renal enlargement in most Group III lesions (89%). It is therefore a useful initial imaging modality in providing information vital to clinical decision making. CONCLUSION: Our experiences suggest that renal bacterial infection may show the continuum of severity from uncomplicated APN to ABN, demonstrated on postcontrast CT scan as wedge-shaped lesions to mass-like lesions, and possibly, finally to frank abscess formation. We classify ABN into three subgroups according to CT findings, and good correlation with clinical severity is demonstrated. These findings deliver valuable concepts regarding the pathophysiology and clinical management of this disease.

Acute Disease

[Parathyroid storm: report of two cases].

Parathyroid storm in patients with primary hyperparathyroidism has previously been described as hyperparathyroid crisis, parathyroid intoxication or acute hyperparathyroidism. Whatever the nomenclature, all emphasize the severity and urgency of this disease entity. Although fewer than 200 cases have been described since the first report by Dawson in 1932, it is generally agreed that parathyroid storm is more prevalent than commonly appreciated. The symptoms and signs of the syndrome are not only due to the hypercalcemia, but also to the toxic effects of the parathyroid hormone (PTH). Its wide, but nonspecific clinical presentations make it easily confused with other cardiovascular or renal diseases. The mortality rate in untreated cases of parathyroid storm is essentially 100%. With combined medical-surgical treatment, it is still reported to be as high as 40%. Two patients with parathyroid storm were encountered at our institute recently, they both presented with severe hypercalcemia, consciousness disturbance and acute renal failure. The serum level of the intact form of PTH (iPTH) in both patients was greater than 1,000 pg/mL. Case 1, a 63-year-old female, presented with hypercalcemic crisis. Initially, good responsiveness to a saline infusion, steroids and furosemide administration was noted. Unfortunately, she became comatous after fine-needle aspiration of the parathyroid tumor. The recurrent storm was refractory to medical therapy, but was treated successfully by surgical removal of the single adenoma. This is a rare reported case regarding a hyperparathyroid storm after fine-needle aspiration of a parathyroid adenoma.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease

Mycotic aneurysm rupture: report of four cases.

"Mycotic" aneurysm was originally described by Osler in 1885. It occurs in a normal or atherosclerotic artery from septic emboli in patients with infective endocarditis. However, now the term "mycotic" aneurysm is applied to all cases of aneurysms caused by any organisms. From September 1988 to November 1990, four cases of ruptured mycotic aneurysm were diagnosed at our institute. Three were males and one was a female; they were elderly with atherosclerosis of the aorta. The diagnosis was established by computed tomography (CT) scan, bacteriology or operative findings. Two of the patients underwent emergency operation; only one survived. In general, the diagnosis of mycotic aneurysm is based on the classical features of fever, abdominal or chest pain, positive blood culture and a pulsatile mass. Because the clinical manifestations are often variable, a patient may present with chronic sepsis (esp. Salmonella sp) of unknown origin with deterioration to a fatal outcome from the aneurysmal rupture, which is a rare cause of retroperitoneal abscess or pericardial effusion. The principles of management, including high clinical suspicion, an accurate diagnosis by imaging studies (arteriography or CT scan), prolonged effective antibiotic therapy, arterial ligation or wide excision of the infected lesion, intraoperative Gram's stain and culture, extra-anatomic bypass grafting through clean tissue planes, and prolonged postoperative follow-up, are indispensable to reduce morbidity and mortality.

Aged

Caroli's disease and congenital hepatic fibrosis associated with polycystic kidney disease. A case presenting with acute focal bacterial nephritis.

Congenital cystic dilatation of the intrahepatic biliary ducts (Caroli's disease), until recently, has been infrequently recognized. It is often associated with autosomal recessive polycystic kidney disease (ARPKD) and congenital hepatic fibrosis (CHF). We hereby report a case with Caroli's disease, polycystic kidney disease (PKD), and CHF: This 24-year-old female patient initially presented with acute bacterial nephritis (ABN). Renal ultrasonography revealed bilateral enlarged kidneys with multiple cysts. Because her parents showed no renal cyst on ultrasonographic examination, she received further studies. Abdominal ultrasonography showed cystic dilatation of the biliary tree. Computed tomography (CT) with meglumine lotroxinate (biliscopin) infusion study and hepatobiliary scintigraphy confirmed the diagnosis of Caroli's disease. Liver biopsy revealed CHF: The radiographic and scintigraphic pictures are hereby illustrated and CT with biliscopin infusion study is emphasized. We conclude that if radiologic evidence of renal cystic lesions is absent in the parents of patients with PKD, the coexistence of Caroli's disease and CHF should be considered. The clinical pictures of ABN in this patient are also discussed. As far as we know, this is the first reported case of ABN in a patient with PKD and Caroli's disease, and it showed good response to antibiotic therapy.

Adult

Mixed acid fermentation of glucose as a mechanism of emphysematous urinary tract infection.

Emphysematous pyelonephritis is a severe necrotizing infection that usually occurs in patients with diabetes mellitus or obstructive uropathy. Although glucose fermentation has been considered as the main cause of gas production the actual mechanism remains controversial. Compositions of gas samples from 2 patients with emphysematous pyelonephritis recently encountered were analyzed, and showed 15% hydrogen, 4.8% carbon dioxide, 60% nitrogen, 6.7% oxygen and some unknown gases in case 1, and 3.4% hydrogen, 22% carbon dioxide, 66% nitrogen and 9.8% oxygen in case 2. These results tend to implicate mixed acid fermentation of glucose as the pathway by which emphysematous urinary tract infections develop.

Aged

Gas-forming vertebral osteomyelitis in diabetic patients.

We report 2 cases of gas-forming vertebral osteomyelitis in diabetic patients. Both were caused by gram-negative bacilli, Escherichia coli and Klebsiella pneumoniae respectively. Both ran a fulminant course to death despite appropriate parenteral antibiotics. We suggest that early surgical intervention may be needed in cases with gas-forming vertebral osteomyelitis.

Aged

Bioelectrical impedance analysis of nutritional status in uremic patients on regular hemodialysis.

The body composition of uremic patients on regular hemodialysis (HD) therapy was studied using the bioelectrical impedance analysis (BIA) technique. The accuracy of BIA in estimating fluid loss during HD was also studied. Thirty-five uremic patients (28 men and 7 women), regularly treated by hemodialysis (HD), were enrolled. The uremic patients had lower serum albumin levels and a marginally lower arm muscle circumference (AMC; p = 0.06) than 107 age- and sex-matched normal control subjects (86 men and 21 women). Before HD, the uremic patients presented with a similar percentage of body fat (BF), fat-free mass (FFM) and total body water (TBW) as normal controls, but they possessed a lower percentage of TBW and FFM, and a higher percentage of BF after HD. When BIA was applied to estimate the fluid loss during HD, overestimation usually occurred. A good correlation between the body fluid loss estimated by the BIA method (BIAL) and that estimated by the body weighing method (BWL) was noted. An equation of BWL = 0.452 BIAL + 0.844 (n = 35, R = 0.85, SEE = 0.58, p less than 0.0001) was derived following linear regression analysis. The weight of BF estimated by BIA before and after HD demonstrated a good correlation (n = 35, R = 0.98, p less than 0.0001). In conclusion, uremic patients on regular HD therapy seem to have decreased serum albumin levels and decreased AMC in anthropometry. After HD, they possess a lower percentage of FFM and TBW than normal controls. The results suggest that accelerated protein catabolism is a common problem in uremic patients on regular HD therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Decrease of catecholamine and neuropeptide Y-like immunoreactivity in the glycerol-induced acute renal failure of rats.

Changes of catecholamine and neuropeptide Y (NPY) were investigated in experimental acute renal failure (ARF) of rats. Concentrations of noradrenaline (NA) and dopamine (DA) were determined by chromatographic analysis using electrochemical detection. Renal content of NPY, identified by radioimmunoassay, was expressed as NPY-like immunoreactivity (NPY-LI). All animals with a plasma urea value higher than 200 mg/dl induced by injection of glycerol were employed as ARF subjects for the experiment. Formation of ARF was also confirmed by histological findings showing diffused necrosis of tubular epithelia. In ARF rats, renal contents of NA and DA decreased markedly (P less than 0.001), NA (ng/g wet tissue) decreased from 186.3 +/- 19.6 to 2.81 +/- 0.67 (n = 8), and DA (ng/g wet tissue) decreased from 14.69 +/- 4.97 to 4.05 +/- 2.66 (n = 8). Similarly, NPY-LI (pg/g wet tissue) in ARF was reduced significantly (P less than 0.001) from 435.23 +/- 35.82 to 4.61 +/- 0.52 (n = 8). The decrease of NA in ARF was obtained parallel to the change of NPY-LI; degeneration of adrenergic nerve fibers was confirmed by immunohistochemical observation. Results obtained suggest damage to the adrenergic and the dopaminergic innervation in the kidneys during ARF.

Acute Kidney Injury

In vivo inhibition of tumor growth of B16 melanoma by recombinant interleukin 1 beta. I. Tumor inhibition parallels lymphocyte-activating factor activity of interleukin 1 beta proteins.

Seven daily intratumoral injections of human recombinant interleukin 1 beta (rHu-IL 1 beta) inhibit the growth of B16 melanoma in syngeneic female C57BL/6 mice. Inhibition was dose dependent and ranged from 36% to 93%. Other routes of injection of rHu-IL 1 beta (intramuscular, intraperitoneal, intradermal) inhibited tumor growth but to a lesser degree (27% to 50%). Two different rIL 1 beta s, one a mutein of rHu-IL 1 beta (Glu-4) and the other one murine IL 1 beta (rM-IL 1 beta), were tested in the tumor inhibition model. rM-IL 1 beta inhibited tumor growth at lower concentrations than did rHu-IL 1 beta and also had enhanced IL 1 activity in the thymocyte assay in vitro. The mutein of rHu-IL 1 beta (Glu-4) had significantly reduced in vitro IL1 activity and did not inhibit tumor growth. No cytotoxic or cytostatic effects of rHu-IL 1 beta were observed in in vitro assays. These results suggest that rHu-IL 1 beta has antitumor activity in vivo that is probably not due to its direct effects on B16 cells but rather is mediated by secondary effects of IL 1 beta.

Animals

Systemic interleukin I administration suppresses arachidonic acid-induced ear oedema in the mouse.

Recombinant human interleukin 1 beta (IL-1 beta), given intraperitoneally to mice as a single injection, significantly suppressed the development of arachidonic acid (AA)-induced ear oedema. This effect was noted 2 h after administration and for at least 5 days afterwards. IL-1 beta was effective in the dose range of 250 ng-20 micrograms/mouse. Injection of IL-1 beta per se resulted in erythema of the ears, and thus, IL-1 beta has the capacity not only to induce and augment but also to suppress inflammatory responses. Indomethacin administered as subcutaneously-implanted pellets did not influence the IL-1 beta induced-ear erythema, but suppressed to some extent the effect of IL-1 beta on the AA-induced ear oedema.

Animals

The inhibitory effect of gossypol on human sperm motility: relationship with time, temperature and concentration.

The inhibitory effect of gossypol acetic acid on human sperm motility was studied with a transmembrane migration method. Gossypol decreased sperm motility after it had been incubated with semen for more than 15 min. However, when sperm motility was evaluated immediately after semen had been mixed with gossypol, no inhibitory effect could be found. We consider that the sperm immobilizing potency of gossypol is much less than our previously studied sperm immobilizing agents. It is unlikely that gossypol can be developed as a vaginal spermicide. The importance of time course in the pharmacological study of sperm motility is emphasized in this study.

Gossypol

Interleukin 1-induced, T cell-mediated regression of immunogenic murine tumors. Requirement for an adequate level of already acquired host concomitant immunity.

Intraperitoneal injection of human rIL-1 in a dose of 0.5 microgram daily for 5 d, or 1 microgram daily for 3 d, was capable of causing complete regression of immunogenic SA1 sarcoma growing subcutaneously in syngeneic or semisyngeneic mice. Higher doses of IL-1 were not more therapeutic against the SA1 sarcoma, but needed to be given to cause complete regression of the immunogenic L5178Y lymphoma. On the other hand, the P815 mastocytoma was much less responsive to IL-1 therapy, in that it failed to undergo complete regression in response to doses of IL-1 capable of causing regression of the L5178Y lymphoma. IL-1 caused regression of the SA1 sarcoma when given on days 6-8 of tumor growth, but not when given on days 1-3. This refractoriness of a small tumor to IL-1 therapy suggests that the antitumor action of IL-1 is based on an underlying host-immune response that is not generated until after day 3 of tumor growth. Direct evidence for the participation of host immunity in IL-1-induced tumor regression was supplied by results showing that IL-1 was not therapeutic against the SA1 sarcoma growing in T cell-deficient (TXB) mice, unless these mice were first infused with Ly-2+ and L3T4+ T cells from donor mice bearing an established SA1 sarcoma. In contrast, normal T cells, or T cells from donor mice bearing a YAC-1 lymphoma, failed to provide TXB recipients with the ability to cause regression of their SA-1 sarcoma in response to IL-1 treatment. The results are in keeping with the interpretation that exogenous IL-1, by augmenting the production of tumor-sensitized T cells, converts a subtherapeutic level of host immunity to a therapeutic level. The results suggest, in addition, that IL-1 only stimulates the replication of T cells that are already engaged in the antitumor immune response.

Animals

Characterization of murine IL-1 beta. Isolation, expression, and purification.

One cDNA clone encoding a truncated murine IL-1 beta (M IL-1 beta) sequence was isolated from a murine macrophage cDNA library. We reconstituted the coding sequence of the 152-residue mature protein and expressed it in Escherichia coli. rM IL-1 beta was purified to homogeneity and characterized by oligonucleotide and NH2-terminal sequence analysis. Purified rM IL-1 beta exhibited biologic activity equivalent to 7.8 x 10(7) units/mg in the murine thymocyte proliferation assay and 9.9 x 10(3) units/mg in the human gingival fibroblast PGE2 production assay, indicative of species specificity. The isoelectric point of rM IL-1 was found to be 8.85. The circular dichroism spectrum revealed that the secondary structure of M IL-1 is indistinguishable from that of the human protein. Receptor binding studies indicated the rM IL-1 bound to murine EL-4.1 thymoma cells in a specific and dose-dependent fashion with an affinity of 32 pM. Competition binding data suggested that murine and human IL-1 compete for a single class of receptor. Antisera were generated in rabbits against both murine and human IL-1. Results of ELISA binding and antisera neutralization assays indicated that there are common antigenic sites between the two IL-1 beta molecules. These domains are of functional importance because they are capable of mediating the neutralization of biologic activity.

Amino Acid Sequence

A biochemical and kinetic analysis of the interleukin-1 receptor. Evidence for differences in molecular properties of IL-1 receptors.

This study describes the biochemical characterization and kinetic analysis of the interleukin-1 (IL-1) receptor in Raji human B-lymphoma and EL4 murine T-lymphoma cells. The internalization of 125I-IL-1 was studied in both cell types by an acid extraction technique which removes surface bound ligand. At 37 degrees C, binding to Raji IL-1 receptors was almost entirely cell surface (91%). EL4 cells, in contrast, internalized 59% of ligand at this temperature and this was almost totally inhibited by sodium azide. Receptor binding studies showed that the B-cells had a lower binding affinity but much higher receptor density per cell (KD = 2.1 nM, Ro = 7709) than the T-cells (KD = 0.4 nM, Ro = 241). The receptor binding affinity of two IL-1 analogs, Glu-4 and clone 18, was determined in competitive binding studies. In the B-cells the analogs had binding affinities of 25 and 90%, respectively, whereas in the T-cells the affinities were 0.2 and 200%, respectively. Chemical cross-linking studies showed that the IL-1 receptor in B-cells had a lower molecular weight than that in T-cells (68 kDa compared to 80 kDa). In summary these studies demonstrate that structural differences exist between IL-1 receptors in Raji and EL4 cells.

Animals

Muteins of human interleukin-1 that show enhanced bioactivities.

Using recombinant DNA techniques, we have made a series of amino-terminal muteins of human interleukin-1 (IL-1). Two of the muteins demonstrated 4-7-fold increase in bioactivity as compared to that of the native IL-1. The enhanced biological potency coincides with an increase in both receptor binding affinity and in vivo tumor inhibitory activity. By site specific mutagenesis, we have shown that the arginine at the fourth position of IL-1 is one of the key residues in the function of IL-1. Circular dichroism studies of the amino-terminus analogs showed little structural rearrangement. The change in bioactivity might be due to a change in the stability of the muteins, in the side chain interactions with receptors or in the minor change in folding near the receptor binding site.

Amino Acid Sequence

High-level expression in Escherichia coli of a soluble and fully active recombinant interleukin-1 beta.

A complementary DNA sequence encoding monocyte interleukin-1 (IL-1), beta form/pI7, was expressed in Escherichia coli. Recombinant plasmid pDP516 was constructed by cloning and rebuilding the mature IL-1 coding sequence into an E. coli expression vector. Bacteria transformed with pDP516 constitutively produced recombinant IL-1 (r-IL-1) at 15-20% of total E. coli protein. The r-IL-1 was found to be in the soluble fraction of sonicated E. coli Bacterial r-IL-1 (DP516) has been purified to homogeneity by anion exchange and sizing column chromatography, with an apparent molecular weight of 17,500. The identity of the purified r-IL-1 was confirmed by amino acid and DNA sequencing analyses. Purified recombinant IL-1 DP516 exhibits biological activity similar to that of native monocyte IL-1 (3 approximately 4 X 10(7) units/mg). An amino-terminal deletion mutant completely abolishes the biological activity, indicating that the integrity of the IL-1 molecule might be important for its function.

Amino Acid Sequence

The inhibitory effect of some ionophores on human sperm motility.

The inhibitory effect of five ionophores, namely, A23187, nonactin, nigericin, monensin and m-chlorocarbonyl cyanide phenylhydrazone, on human sperm motility were measured with a trans-membrane migration method. The concentrations of A23187 and nigericin that decreased sperm motility to 50% of control were 20 microM (10.5 mg/l) and 8 microM (5.8 mg/l), respectively. Because these two ionophores were more potent than previously reported membrane-active sperm-immobilizing agents, we propose that ionophores could be a new category of vaginal contraceptive if a pharmaceutical preparation that is safe to be administered in vivo can be developed.

Anti-Bacterial Agents