Processing of MOPC 315 immunoglobulin A oligosaccharides: evidence for endoplasmic reticulum and trans Golgi alpha 1,2-mannosidase activity.

The processing of asparagine-linked oligosaccharides on the alpha-chains of an immunoglobulin A (IgA) has been investigated using MOPC 315 murine plasmacytoma cells. These cells secrete IgA containing complex-type oligosaccharides that were not sensitive to endo-beta-N-acetylglucosaminidase H. In contrast, oligosaccharides present on the intracellular alpha-chain precursor were of the high mannose-type, remaining sensitive to endo-beta-N-acetylglucosaminidase H despite a long intracellular half-life of 2-3 h. The major [3H]mannose-labeled alpha-chain oligosaccharides identified after a 20-min pulse were Man8GlcNAc2 and Man9GlcNAc2. Following chase incubations, the major oligosaccharide accumulating intracellularly was Man6GlcNAc2, which was shown to contain a single alpha 1,2-linked mannose residue. Conversion of Man6GlcNAc2 to complex-type oligosaccharides occurred at the time of secretion since appreciable amounts of Man5GlcNAc2 or further processed structures could not be detected intracellularly. The subcellular locations of the alpha 1,2-mannosidase activities were studied using carbonyl cyanide m-chlorophenylhydrazone and monensin. Despite inhibiting the secretion of IgA, these inhibitors of protein migration did not effect the initial processing of Man9GlcNAc2 to Man6GlcNAc2. Furthermore, no large accumulation of Man5GlcNAc2 occurred, indicating the presence of two subcellular locations of alpha 1,2-mannosidase activity involved in oligosaccharide processing in MOPC 315 cells. Thus, the first three alpha 1,2-linked mannose residues were removed shortly after the alpha-chain was glycosylated, most likely in rough endoplasmic reticulum, since this processing occurred in the presence of carbonyl cyanide m-chlorophenylhydrazone. However, the removal of the final alpha 1,2-linked mannose residue as well as subsequent carbohydrate processing occurred just before IgA secretion, most likely in the trans Golgi complex since processing of Man6GlcNAc2 to Man5GlcNAc2 was greatly inhibited in the presence of monensin.

[Life experience of adults with unilateral agenesia of the forearm: effect of prosthesis on self image and social relations]. / Parcours de vie d'adultes présentant une agénésie unilatérale d'avant-bras: enjeux et incidence du recours à la prothèse sur l'image de soi et les relations sociales.

PURPOSE OF THE STUDY: This study was devoted to better understanding how adults with agenesia of the forearm live their condition. The malformation studied was identical to that of a previous study in children. The present study was designed to provide professionals and parents with a reference system for making therapeutic decisions. MATERIAL AND METHODS: An intensive survey using semi-directive interviews was conducted among adults aged 19 to 37 years, 12 women and 8 men, with unilateral agenesia of the forearm. The majority of the participants had an occupation and an active social and familial life. RESULTS: The survey revealed factors of limitation or progress, expectations and renouncements, marking the life experience of these persons. The prosthesis had a significant impact on their lives. DISCUSSION: Four types of life experience could be identified from the survey data. All four could be understood as a search for equilibrium between internal reality (desired self image) and external reality (image produced by the physical and human environment via the regards of others and obstacles encountered). Several modalities for using a prosthesis, several ways of coping with the absence of a hand, with or without a prosthesis, and several ways of constructing a self-representation were distinguished. Rather than a functional disability, agenesia was found to be perceived as a persistent problem in daily life, generating handicap- or discrimination-producing situations. CONCLUSION: Forearm agenesia creates a situation different from normal and as such makes the question of self-identity and social relations more complex than for others. The comments provided by these young adults who cope with the paradoxical condition of an amputated but functional body demonstrated the central role of the body.

Sequential hemodynamic changes in end-stage renal disease and the anephric state during volume expansion.

The sequence of hemodynamic events during periods of salt- and water-loading was studied in anephric patients and those with end-stage kidney disease. The 10 patients studied showed four different sequential hemodynamic patterns: 1) no significant increase in blood pressure (BP) in two patients; 2) increase in BP associated with an increase in cardiac output and without change in total peripheral resistance in two patients; 3) increase in BP associated with an increase in total peripheral resistance from the beginning without an increase in cardiac output in five patients; and 4) increase in BP associated with an initial increase in cardiac output followed by an increase in total peripheral resistance in one patient. There was a significant positive correlation between BP and blood volume and between BP and total exchangeable sodium in the patients in whom salt- and water-loading increased the BP. It is concluded that during salt- and water-loading an initial rise in cardiac output is not necessary to increase BP and that a sustained rise in cardiac output does not always increase the total peripheral resistance. Mechanisms other than whole-body autoregulation play a role in increasing BP during salt- and water-loading in patients deprived of renal excretory function.

Circadian relationships between circulating atrial natriuretic peptides and serum calcium and phosphate in healthy humans.

Long-acting natriuretic peptide (LANP), vessel dilator (VSDL), and atrial natriuretic factor (ANF) consisting of amino acids (aa) 1 to 30, 31 to 67, and 99 to 126, respectively, of the 126-aa ANF prohormone circulate in humans. Among the biologic properties of these peptides is the ability of ANF to decrease intracellular calcium concentrations. To determine if atrial natriuretic peptides are directly related to serum calcium and/or phosphate in healthy normocalcemic humans, we examined 21 24-hour profiles of VSDL, LANP, ANF, and serum calcium and phosphate in 14 healthy humans. VSDL, LANP, and ANF each had significant (P < .001) circadian rhythms, with peak concentrations late during sleep (at 4:00 AM) being nearly twice the concentrations in the afternoon and evening. Serum calcium and phosphate also had significant circadian rhythms (P < .001) with troughs nearly opposite to those of the atrial natriuretic peptides, suggesting that atrial peptides may be important in the modulation of the circadian rhythms of calcium and phosphate. The nearly identical circadian rhythms of the atrial natriuretic peptides and of parathyroid hormone (PTH) reported by others, along with evidence that PTH may increase atrial peptide release, suggest that some of the effects attributed to PTH may be mediated by atrial natriuretic peptides.

Effective long-term suppression of pituitary-gonadal axis in prostatic cancer by Zoladex (ICI 118,630).

Eleven patients with prostatic cancer maintained on monthly depot Zoladex (ICI 118,630) from 20 to 23.5 months are described. All are in clinical remission. Castrate levels of testosterone are maintained, and low levels of LH and FSH were observed. Contrary to a prior report, persistent blockage of the pituitary-gonadal axis is achieved and maintained with no detectable adverse side effects.

Further study of fibrinogen degradation products in bladder cancer detection.

A new, rapid immunoassay kit for assaying fibrinogen degradation products (FDP) was studied in 56 patients with cancer of the bladder and in 48 control patients. The specificity of the kit was demonstrated with a small number of false positive results. In bladder cancer patients with low-stage, small superficial tumors, FDP was positive in 32.2 per cent. The combination of urinary cytologic examination with FDP increased the accuracy of the positive results to 80 per cent. The rapid FDP test supplements the urinary cytology in the follow-up and detection of early bladder cancer.

Zoladex (ICI 118,630): clinical trial of new luteinizing hormone-releasing hormone analog in metastatic prostatic carcinoma.

Twenty-seven patients with metastatic adenocarcinoma of the prostate were treated with the new luteinizing hormone-releasing hormone analog, Zoladex (ICI 118,630) for up to ninety-eight weeks. Initially, treatment was randomized between Zoladex 250 micrograms and 500 micrograms self-injected subcutaneously every day for a minimum period of twelve weeks following which a sustained-release, once-monthly depot formulation of Zoladex 3.6 mg s.c. was used. Acute rises in serum gonadotropins and testosterone during the first two days were followed by declines in hormone levels over the following three weeks. Median time to castration with 500 micrograms/day was twenty-two days compared with forty-three days with 250 micrograms/day (p = 0.06). No significant endocrinologic changes occurred during the transfer to the depot, and serum testosterone remained 95 per cent suppressed throughout the duration of the study. After three months the median daily serum Zoladex concentrations ranged between 0.47 and 0.53 ng/ml and were not significantly different among the three dosage forms. No specific correlation among serum Zoladex concentrations, endocrinologic parameters, and tumor response rates were found. Hot flashes initially, and decreased libido were the only common complaints. Zoladex was well tolerated, and no side effects required dose-modification or removal from the study. Tumor response rates up to one year appeared to be comparable to the conventional endocrine therapies. This analog in monthly depot formulation is recommended for further clinical evaluation.

Mental confusion in a patient treated with metronidazole--a concentration-related effect?

We report a case of serious mental confusion, hallucinations, and agitation in a 65 year old man, occurring in close relationship to the intravenous administration of metronidazole. The patient was treated twice, but at different dosages. The confusion and hallucinations occurred at the recommended daily dose of 2.0 g, but did not return at a daily dose of 500 mg. Metronidazole serum concentrations were obtained throughout both courses of therapy; CSF and tissue concentrations were obtained at autopsy. The mental confusion was associated with peak serum concentrations of approximately 40 micrograms/ml. Symptoms resolved within 24-48 hr after stopping metronidazole, and resolution was consistent with a metronidazole half life of 14 hr. We conclude that metronidazole can be associated with a dose- and serum concentration-related mental confusion state, and that this side effect appears completely reversible upon discontinuing the drug.

Reference values for circadian rhythms of 98 variables in clinically healthy men in the fifth decade of life.

Nine clinically healthy men, 41-47 yr of age, served as subjects in a 24-hr study conducted at the Edward Hines Jr Veterans Administration Hospital in the Chicago area in May 1988. Physiologic measurements, and blood and urine samples were collected at 3-hr intervals over a single 24-hr period beginning at 1900. The number of variables measured or calculated (total = 98) included: 6 vital signs (oral temperature, pulse, blood- and intraocular pressures); 16 in whole blood (counts and differentials); 50 in serum (SMAC-24, lipids, hormones, electrophoresis of LDH and proteins); and 26 in urine (solids, proteins, creatinine, catecholamines, melatonin, cortisol, electrolytes and metals). Data were analyzed for time effect by analysis of variance (ANOVA) and for circadian rhythm by single cosinor. Individual rhythm characteristics for each variable were summarized for the group by population mean cosinor. The vast majority of variables revealed statistically significant within-day changes in values as validated by one-way ANOVA. All vital signs (except for intraocular pressures) and all serum hormones displayed a prominent circadian rhythm for the group, as did most variables in whole blood, while only about half of the variables in urine demonstrated a significant group rhythm. The results obtained are meant to: (a) document the circadian time structure; and (b) serve as reference values for circadian rhythm characteristics (range of change, mesor, amplitude and acrophase) for a defined group of individuals: clinically-healthy adult men in the prime of life.

Ten-year-replicated circadian profiles for 36 physiological, serological and urinary variables in healthy men.

At 3-hr intervals over a 24-hr span, 36 systemic, serologic and urinary variables were examined in 7 men in their mid 20's in the Spring of 1969, and again in the same 7 men in the Spring of 1979 under a similar chronobiologic protocol, using the same chemical and numerical analytical procedures. The variables examined for rhythms by cosinor were: vital signs--blood pressure (systolic, diastolic, pulse pressure and mean arterial pressure), heart rate, intraocular pressure (left and right), oral temperature; serum components--albumin, albumin/globulin ratio, total bilirubin, calcium, carbon dioxide, chlorides, bilirubin, cholesterol, globulin, glucose, potassium, sodium, sodium/potassium ratio, transaminase, triglycerides, total protein, urea nitrogen; and urine components--calcium, calcium/magnesium ratio, creatinine, magnesium, pH, potassium, sodium, sodium/potassium ratio, urea clearance, urea nitrogen, volume and zinc. Although all subjects appeared clinically healthy in 1969 and in 1979, certain inter-study differences were observed in a number of rhythm parameters of different variables. Statistically significant increases in mesor for the group as a whole were observed for serum Ca, cholesterol, Cl, CO2, K, Na, and while statistically significant mesor decreases for a group as a whole were noted in serum glucose and transaminase. Statistically significant increases in amplitude for the group as a whole were observed in serum chloride and urinary Na/K ratio, while statistically significant decreases were observed in amplitude for blood pressure, heart rate, serum albumin, A/G ratio, globulin, glucose, protein, sodium and transaminase.(ABSTRACT TRUNCATED AT 250 WORDS)

The circadian rhythm of the N-terminus and C-terminus of the atrial natriuretic factor prohormone.

Circadian variation in the circulating concentrations of the N-terminal and C-terminal portions of the atrial natriuretic factor prohormone (pro ANF) was evaluated in 8 men, ages 41-47, who have been followed for 19 years with respect to circadian variation in physiological variables including blood pressure and clinical chemistries. The N-terminus of the ANF prohormone contains two peptides consisting of amino acids 1-30 and 31-67 while the C-terminus contains 1 peptide (amino acids 99-126) of this 126 amino acid prohormone which lower blood pressure and have natriuretic properties. To determine if either the N-terminus and/or the C-terminus of the prohormone have a circadian variation in their circulating plasma concentrations these 8 men had blood samples obtained for radiommunoassay every 3 hr during a 24-hr period. Three radiommunoassays which immunologically recognize (1) the whole N-terminus (i.e. amino acids 1-98), (2) the midportion of the N-terminus (amino acids 31-67) and (3) the C-terminus (amino acids 99-126) of the ANF prohormone were utilized. The whole N-terminus, the midportion of the N-terminus which circulates after being proteolytically cleaved from the rest of the N-terminus, and the C-terminus each had a peak circulating concentration between 0400 and 0700 which were significantly (P less than 0.001) higher than their concentrations at any other time throughout the 24-hr period.(ABSTRACT TRUNCATED AT 250 WORDS)

Circadian distribution of proteins in urine from healthy young men.

Urine samples were collected at 3-hr intervals over a single 24-hr period from each of seven clinically healthy men who ranged in age from 21-25 years. Urines at each collection time were subsequently pooled using 20% of each volume and serially dialyzed against ammonium-barbituric acid buffer (pH 7.35 +/- 0.02), using a cellulose membrane permeable to compounds of less than 12,000-14,000 molecular weight (mw). When the dialyzed portions were then analyzed for total proteins, the sum of proteins in eight pools amounted to 74 mg. A 1 ml aliquot of each pool, representing approximately 50 micrograms of proteins, was concentrated and reconstituted. Approximately 20 micrograms of reconstituted proteins were then subjected to polyacrylamide gel electrophoresis. The stained gel was then scanned by laser densitometry and planimetry. Each aliquot revealed eight segments as identified by Coomassie and silver staining. Their molecular weights, estimated by extrapolation from concurrently run protein standards, and their total protein amounts were: 116,000 mw (9.44 mg), 91,000 mw (3.3 mg), 68,000 mw (11.58 mg), 53,000 mw (2.58 mg), 43,000 mw (9.12 mg), 32,000 mw (7.13 mg), 24,000 mw (4.52 mg) and 20,000 mw (5.27 mg). A statistically significant rhythm (P = 0.022 from ANOVA and 0.011 from Single Cosinor) was found for the excretion of total proteins, with an acrophase in the afternoon (1537) for these diurnally-active subjects.

The lateral notch sign associated with acute anterior cruciate ligament disruption.

We prospectively studied all of the patients with anterior cruciate ligament disruptions who sought treatment at the senior author's office during a 36-month period. Plain radiographs identified depressions measuring 2 mm or more in the lateral femoral condyle (lateral notch sign) in 9 of 120 knees (7.5%) with acute anterior cruciate ligament disruption and in 2 of 44 knees (4.5%) with chronic pivot shift instability. The depression ranged from 2 to 6 mm deep and from 20 to 25 mm long. The mean age for acutely injured patients with lateral notch signs was 17.2 years, 6 years younger than the mean age of the group with acutely injured anterior cruciate ligaments as a whole. Ten of the 11 patients (91%) with lateral notch signs were men, and all 6 patients with depressions shallower than prior descriptions of the notch sign were men. In contrast, 67% (N = 110) of the entire group of patients who had anterior cruciate ligament disruption were men. Ten of the 11 patients (91%) with the lateral notch signs and 4 of the 6 patients (66%) with minimal depressions also had lateral meniscus tears, while 58 of 147 patients (39%) without lateral femoral condyle depression had lateral meniscus tears. Previous reports that the lateral notch is a sign of chronic anterior cruciate ligament deficiency with recurrent pivot shifts are not supported by the number of prospectively recognized acute lateral femoral notch signs in this series. We found the presence of radiographic changes in the lateral femoral condyle to have statistically significant correlations with young age, male sex, lateral meniscus tears in general and anterior-horn lateral meniscus tears specifically, and lateral femoral chondral lesions.

Instrumental analysis of trace elements in thumbnails of human subjects.

Human thumbnails were analyzed for trace elements by instrumental analysis using thermal neutron activation technique. The average concentration of metals studied in clinically symptom-free adult female and male subjects were: zinc, 184 vs. 153 ppm; chromium, 6.8 vs. 4.2; selenium, 0.9 vs. 0.6; gold, 2.6 vs. 0.4; mercury, 1.9 vs. 0.4; silver, 0.7 vs. 0.3; cobalt, 0.07 vs. 0.04. A summary of literature reported concentration of metals in human nail is also presented.

Sodium diethyldithiocarbamate (imuthiol) and cancer.

Sodium diethyldithiocarbamate (imuthiol), a nonantigenic, nontoxic and noncarcinogenic compound, evinces distinctive properties in recruitment and activation of T cells, and no direct influences on B cells or macrophages. The biological attributes of imuthiol (destruction of neoplastic cells, bacteria, fungi and parasites; a detoxifying influence against carcinogens or agents toxic for the liver) could strengthen its activity as a biological response modifier. Preliminary clinic testings show that imuthiol restores T cell activities and regulates the ratio among T cell subsets in cancer patients, without untoward side effects.

Assessment of HBV replicative status by receptors for polymerized human albumin.

Receptors for polymerized human albumin (pHSA-r) are expressed on HBsAg in larger numbers during complete viral replication. We have evaluated the usefulness of pHSA-r as a marker of high-level infection by a comparison with serum HBeAg, liver HBcAg and serum HBV-DNA. One-hundred-and-fifty-seven patients with HBsAg positive chronic liver disease were tested for HBeAg and pHSA-r titre. In 73 of them liver HBcAg was tested by immunofluorescence, while in the remaining 84 serum HBV-DNA was determined. Seventy-three subjects were HBeAg positive, 20/73 were HBcAg positive, and 60/84 had circulating HBV-DNA. The best cut-off for pHSA-r was found at 1:204,800 (sensitivity of 67.6% and specificity of 95.7% in detecting viral replication). At this cut-off the concordance rate between pHSA-r and viral replication (as assessed by HBV-DNA or liver HBcAg) was 83%, a figure similar to that of HBeAg (88%). Three HBeAg negative subjects who were actually complete replicators were identified by the pHSA-r test.

Long-term airway space changes after mandibular setback using bilateral sagittal split osteotomy.

Eleven patients were evaluated retrospectively for their long-term changes in hypopharyngeal airway space after surgical correction of mandibular hyperplasia. All patients had undergone mandibular setbacks by way of bilateral sagittal split osteotomies using rigid fixation. The cephalometric evaluation of hypopharyngeal airway space was based on stable craniofacial landmarks. The results of this study indicate that mandibular setback procedures create relative narrowing of the hypopharyngeal airway space, as seen on lateral cephalometric radiographs, which in isolated cases might contribute to the development of an obstructive sleep apnea syndrome. The 2-dimensional evaluation of hypopharyngeal airway space and the clinical implications of the results are discussed.

Chronic ulcers and myasis as ports of entry for Clostridium tetani.

Evaluating tetanus immune status is not yet the usual clinical practice regarding patients with chronic ulcers or myasis. However, of 858 tetanus patients at Hospital Couto Maia (Salvador, Bahia, Brazil) aged 1 year or above, 2 had pressure ulcers and 17 had chronic ulceration of the lower limbs where these skin lesions were the ports of entry for Clostridium tetani. In these 19 cases, the following predisposing factors were described: venous insufficiency (n=6), sickle cell anemia (n=2), Hansen s disease (n=1), malnutrition (n=1), diabetes mellitus (n=1), trauma (n=1) and unknown factors (n=7). In 6 other cases, in addition to the Hansen s disease patient, the port of entry for tetanus was the site of extraction of Tunga penetrans larvae. In these 25 cases, the majority of patients (68%) were over 40 years old (17/25) and all of these patients stated that they had either not followed a tetanus toxoid vaccination regimen (19/25), or had partially completed such a regimen, or did not give precise information (6/25). Among the same series studied, over half (52%) of the patients died (13/25). We conclude that tetanus prevention must be included in the treatment of chronic skin ulcer patients, vaccination coverage should be increased among older people, and strategies aimed at improving coverage for all age groups must be reviewed.

Health physics measurement of Princeton Tokamaks, 1977-1987.

The Princeton Plasma Physics Laboratory (PPPL) began fusion experiments in 1951. In the early years, the major health physics concerns were associated with x radiation produced by energetic electrons in the plasma. Within the past year, neutron and 3H production from 2H-2H (represented hereafter as D-D) reactions has increased significantly on the larger fusion devices. Tritium retention noted in graphite tiles underscores the significance of material selection in present and future 3H-fueled fusion devices. This paper reports on operational health physics radiation measurements made on various PPPL machines over the past 10 y.

[Treatment of anemia in children undergoing chronic hemodialysis with recombinant human erythropoietin]. / Tratamiento de la anemia en niños sometidos a hemodiálisis crónica con eritropoyetina humana recombinante.

Anemia associated to chronic renal failure (CRF) is a very frequent disorder. Twenty five per cent of adult patients under hemodialysis require periodical transfusions to maintain acceptable quality of life. This anemia is due mainly to a relative deficit of erythropoietin (EPO). Thanks to recombinant DNA techniques, EPO availability has made it possible to treat this population with the hormone. Most of the reported experience has been obtained from adult patients and literature on children is scarce. For this reason, a controlled prospective trial on 18 patients (9 males and 9 females) with a mean age of 12.4 years (range 7-17) was conducted, evaluating hematimetric response, safety of treatment and effect on quality of life after one year of treatment. Seventeen patients could be evaluated; mean follow-up was of 365 days (180-323). Treatment started with an administration scheme of 25 U/kg/dose, i.v. route, three times weekly, and dose was corrected according to the hematimetric response. Target hemoglobin was set in 10 g%. Mean dose required to reach target was 101.5 +/- 37.7 U/kg/dose (50-200) three times weekly and time elapsed was of 223.3 days (175-355). Only one patient did not achieve target hemoglobin value with the maximal dose planned (200 U/kg/dose). Bone marrow biopsy in this patient showed alpha widespread fibrosis secondary to hyperparathyroidism caused by CRF. Direct correlation was found between the required rHuEPO dose and basal levels of serum alkaline phosphatase (Table 2). Results obtained in status performance on six patients showed significant increase in all the variables under analysis (Table 4).(ABSTRACT TRUNCATED AT 250 WORDS)