Commentary. Stories that heal, wheel within a wheel.
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Biomedical subjects
Publications and source records attributed to E Schwartz.
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This study characterized the nature of reticulin fibrils from human kidney cortex by immunochemical analysis. Controls consisted of type I collagen fibrils derived from the kidney parietal capsule. Most of the fibrils in the capsule ranged in diameter from 60 to 80 nm whereas reticulin fibrils from the cortex ranged from 30-45 nm. Immunochemistry by light and electron microscopic examinations was carried out with antibodies directed against type I and type III collagens, their corresponding aminopropeptides, and decorin (PG-II). The ratio of type I to type III collagen was determined by cyanogen bromide peptide digests. This study showed that reticulin fibrils are hybrids of type I and type III collagens. Double immunoelectron microscopic examination showed that fibrils 20-25 nm consisted mainly of type I collagen some of which retained their aminopropeptide. Larger fibrils 30-35 nm labeled simultaneously for type I and type III collagens. However, most fibrils with diameters between 40-55 nm labeled for type III collagen and its corresponding aminopropeptide. No decorin was detected at the surface of reticulin fibrils. Purified reticulin consisted of 82% type III and 18% type I collagen whereas collagen derived from the capsule revealed 76% type I and 24% type III. The presence of the aminopropeptide of type III procollagen in reticulin fibrils is a striking feature and may play a role in regulating their diameter.
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The laryngeal mask (LM) is a new concept developed by Brain. Easily inserted, the LM allows appropriate ventilation without the disadvantages of either the facial mask or the endotracheal intubation with its own complications. The limits of its use concern all the cases of reduction of thoracopulmonary compliance and full stomach. The LM offers no protection against regurgitation and aspiration. Airway obstruction may occur following laryngospasm (light anaesthesia) or down folding of the epiglottis. Trauma to the uvula and the posterior pharyngeal wall have been reported. The LM may be useful in all cases of surgery in which intubation is not absolutely required. Moreover, the LM is widely used for ENT and ophthalmic surgeries, in paediatric and adult procedures. Many cases of foreseeable or unforeseeable difficult intubation have been resolved by the insertion of a LM, allowing secondary intubation through the mask. Further investigations are required in order to evaluate the real limits and indications for its extended use.
An acute, severe onset of celiac disease is very unusual in adults. We describe its occurrence postpartum in two patients. These, together with two similar cases previously reported, suggest a causal association with the puerperium. Possible causes include potentiation of a pathogenetic immune reaction and hormonal mechanisms.
The molecular basis of most beta-thalassemia syndromes has been defined, while the spectrum of mutations causing delta-thalassemia is not well characterized. In an attempt to identify such mutations, the region encompassing the delta-globin gene from three Greek Cypriot families suspected of having delta-thalassemia was amplified by polymerase chain reaction (PCR), and DNA sequence determined using an automated fluorescence-based sequencer. Four novel mutations were identified: a G----T change at codon 27 that results in an alanine to serine change; a C----T change at codon 116 converting arginine to cysteine; a T----C change at codon 141 converting leucine to proline; and an AG----GG change at the consensus 3'-acceptor site in IVS-2. While the latter is clearly a thalassemic mutation, the low hemoglobin A2 in the first three may be due to either decreased production or instability of the altered delta-globin chain. All four mutations may be detected by PCR amplification of genomic DNA followed by restriction enzyme digestion. Two mutations abolish restriction sites while two create new cleavage sites. Screening for molecular defects that cause delta-thalassemia or unstable delta-globin by PCR amplification and restriction enzyme digestion will lead to correct diagnosis of beta/delta-thalassemia compound heterozygotes and improved genetic counseling.
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IS150 contains two tandem, out-of-phase, overlapping genes, ins150A and ins150B, which are controlled by the same promoter. These genes encode proteins of 19 and 31 kD, respectively. A third protein of 49 kD is a transframe gene product consisting of domains encoded by both genes. Specific -1 ribosomal frameshifting is responsible for the synthesis of the large protein. Expression of ins150B also involves frameshifting. The IS150 frameshifting signals operate with a remarkably high efficiency, causing about one third of the ribosomes to switch frame. All of the signals required for this process are encoded in a 83-bp segment of the element. The heptanucleotide A AAA AAG and a potential stem-loop-forming sequence mark the frameshifting site. Similar sequence elements are found in -1 frameshifting regions of bacterial and retroviral genes. A mutation within the stem-loop sequence reduces the rate of frameshifting by about 80%. Artificial transposons carrying this mutation transpose at a normal frequency, but form cointegrates at a approximately 100-fold reduced rate.
Tryptic peptide sequences from the 22 kDa polypeptide of tomato LHCI were used to construct a probe for gene cloning. The two genes cloned, cab11 and cab12, encode proteins of 251 and 250 residues that are 88% identical in overall amino acid sequence and 93% identical in the deduced mature protein. Each gene is present in a single copy per haploid genome; cab11 on chromosome 3 and cab12 on chromosome 6, and each has 2 introns located in similar positions to introns in other members of the Chl a/b-binding (CAB) protein gene family. Comparison of the amino acid sequences of LHCI, LHCII, CP29 and CP24 polypeptides confirms that all CABs share two regions of very high similarity which include the first and third transmembrane helices and the stroma-exposed sequences preceding them. However, near the N-terminus and between the conserved regions, the LHCI polypeptides have sequence motifs which appear to be PSI-specific.
In a double-blind study, we compared the postoperative (post-op) blood loss in 161 children undergoing open heart surgery with cardiopulmonary bypass whose immediate post-op transfusion requirements were met with either very fresh whole blood (VFWB), 24- to 48-hour-old whole blood or reconstituted whole blood (packed red blood cells, fresh frozen plasma [FFP], and platelets). Assignment to treatment groups was not strictly random but dependent, in part, on the ability of families to provide directed donors for fresh blood. The three patient groups were comparable with respect to patient age, pre-op coagulation profiles (bleeding time, prothrombin time, activated partial thromboplastin time, platelet count, fibrin split products, fibrinogen, and platelet aggregation tests) difficulty of operative procedures and time spent on CPB. Mean 24-hour post-op blood loss in milliliters per kilogram was 50.9 +/- 9.3 in the VFWB group, 44.8 +/- 6.0 in the 24- to 48-hour-old group, and 74.2 +/- 8.9 in the reconstituted group (p = .03). When blood loss was compared in the 93 children less than 2 years of age, mean blood loss was 52.3 +/- 10.8 in the VFWB group, 51.7 +/- 7.4 in the 24- to 48-hour-old group, and 96.2 +/- 10.7 in the reconstituted group (P = .001). For subjects who had received reconstituted blood, 30-minute and 3-hour post-op platelet aggregation responses to adenosine diphosphate (10 mumol/L) and 30-minute aggregation response to epinephrine (2.5 mumol/L) were more depressed than in the VFWB and 24- to 48-hour groups (P less than .001, P = .005, and P = .02). Comparison of other post-op coagulation tests could not explain the increased blood loss in the reconstituted group. We conclude that the transfusion of less than 48 hours old whole blood is associated with significantly less post-op blood loss than the transfusion of packed red blood cells, FFP, and platelets in children under 2 years old who underwent complex cardiac surgery. The blood losses associated with the transfusion of VFWB and 24- to 48-hour-old blood are comparable and may be, in part, due to better functioning platelets.
Prolonged spontaneous clinical remission in a patient with malignant peritoneal mesothelioma is described. The case is also unique because of the presence of high-spiking fevers as a symptom of tumor recurrence and the finding of an elevated titer of rheumatoid factor in the ascitic fluid. The caution needed in interpreting results of therapeutic interventions in this tumor is emphasized.
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The steady-state levels of mRNA produced by 14 genes encoding members of the tomato chlorophyll a/b binding protein family were quantified. All genes were found to be expressed in leaf tissue, but the mRNAs accumulated to significantly different levels. The transcripts of cab 1A, cab 1B, cab 3A and cab 3B, encoding the Type I LHC proteins of photosystem II, are abundant, while low levels were measured for mRNAs encoding the Type II LHC II and the LHC I proteins. Sequences from the 5' upstream regions (-400 to translational start) of some cab genes were determined in this study, and a total of 16 tomato cab gene promoters for which sequences are now available were analyzed. Significant sequence conservation was found for those genes which are tandemly linked on the chromosome. However, the level of sequence conservation is different for the different cab subfamilies, e.g. 85% similarity between cab 1A and cab 1D vs. 45% sequence similarity between cab 3A and cab 3C upstream sequences. Characteristic GATA repeats with a conserved spacing were found in 5' upstream sequences of cab 1A-D, cab 3A-C, cab 11 and cab 12. The consensus sequence CCTTATCAT, which is believed to mediate light responsiveness, was found at different locations in the upstream sequences of cab 6B, cab 7, cab 8, cab 9, cab 10A, cab 10B and cab 11. In 11 out of 15 genes the transcription initiation site was found to center on the triplet TCA.
Pseudoxanthoma elasticum (PXE) is a heritable disorder of connective tissue that is characterized by redundant folds of skin in flexural areas. There is considerable evidence that suggests that the elastic fiber is the main site of the abnormality although the primary molecular defect has not been identified. The aim of this study was to identify differences between PXE and normal skin elastins. Elastins from normal, nonsolar-exposed skin, and pseudoxanthoma elasticum lesional skin were purified and their solubilization by pancreatic elastase was compared. Results demonstrated that elastin derived from normal skin was more susceptible to proteolytic cleavage than elastin purified from either pseudoxanthoma elasticum lesional skin or ligamentum nuchae. Pretreatment of the lesional elastin with testicular hyaluronidase increased its solubilization two-fold and generated a unique 15,000 Da molecular weight fragment. Elastin prepared from PXE skin may contain bound glycosaminoglycans which interfere with elastase activity. The susceptibility of normal skin elastin to proteolytic degradation may have implications in the study of aging skin.
STUDY OBJECTIVES: To survey faculty attrition in emergency medicine and compare it with faculty attrition in the specialties of orthopedic surgery and cardiology. DESIGN: Chairmen of the three departments were surveyed regarding faculty attrition, work hours, and motivation for leaving. Those emergency physicians having left also were surveyed. MAIN RESULTS: Responses were obtained from 67 of 68 emergency medicine programs, 53 of 58 orthopedic programs, and 47 of 54 cardiology programs. Overall, there were 670 total faculty in emergency medicine, of which 67 (10%) left their positions during 1988-38 to enter private practice, 18 to take another academic position, and 11 to do something unidentified. There was no difference in faculty attrition among the three specialties or in what the physicians left to do (P = .75). Both the orthopedists and the cardiologists worked more total hours each week (P = .001) but fewer night hours (P = .03) than the emergency physicians. Among the 67 emergency medicine programs, 28 reported no attrition; 39 reported one or more physicians leaving the program. These two groups of programs did not differ in terms of faculty size, hours worked, or night hours worked.
Bone marrow examination is often performed in thrombocytopenic children to distinguish immune thrombocytopenic purpura (ITP) from acute leukemia. We describe a patient with thrombocytopenia and 50% common acute lymphoblastic leukemia antigen (CALLA) positivity in his marrow who was subsequently shown to have ITP. CALLA (CD10) is a surface antigen found in early B-lymphocytes and is elevated in most cases of childhood acute lymphoblastic leukemia (ALL). This case prompted us to prospectively study the frequency of immature lymphocyte populations in children with ITP. Fourteen patients with acute ITP and five with other conditions were studied. The two groups were comparable with respect to age: ITP mean, 4.3 (range 0.3-15.5) years; control mean, 5.8 (0.6-13.8) years. The ITP group had a significantly higher percentage of CD10 positive bone marrow lymphocytes (p = 0.007). Five of the 10 patients younger than 4 years of age in the ITP group had CD10 levels of greater than 30%, which is in the leukemic range, whereas none of the control patients had a CD10 levels of greater than 17% (p = 0.003). There was good correlation between CD10 positivity and B4 positivity indicating that both of these markers arise from the same population of immature B-lymphocytes. None of the ITP patients who were older than 4 years had a CD10 level of greater than 30%. We conclude that it is common to have an increase in the proportion of immature lymphocytes in the marrow of young children with ITP. The cause of this increase in CD10 positive cells is unknown.(ABSTRACT TRUNCATED AT 250 WORDS)
Soybean plants (Glycine max [L.] Merr. cv Clark) carrying nuclear and cytoplasmic "stay-green" mutations, which affect senescence, were examined. Normally, the levels of chlorophyll (Chl) a and b decline during seedfill and the Chl a/b ratio decreases during late pod development in cv Clark. Plants homozygous for both the d(1) and d(2) recessive alleles, at two different nuclear loci, respectively, retained most (64%) of their Chl a and b and exhibited no change in their Chl a/b ratio. Combination of G (a dominant nuclear allele in a third locus causing only the seed coat to stay green during senescence) with d(1)d(2) further inhibited the loss of Chl in the leaf. Whereas the thylakoid proteins seem to be degraded in normal Clark leaves during late pod development, they were not substantially diminished in d(1)d(2) and Gd(1)d(2) leaves. In plants carrying a cytoplasmic mutation, cytG, Chl declined in parallel with normal cv Clark; however, the cytG leaves had a much higher level of Chl b, and somewhat more Chl a, remaining at abscission, enough to color the leaves green. In cytG, most thylakoid proteins were degraded, but the Chl a/b-binding polypeptides of the light-harvesting complex in photosystem II (LHCII), and their associated Chl a and b molecules, were not. Thus, the combination of d(1) and d(2) causes broad preservation of the thylakoid proteins, whereas cytG appears to selectively preserve LHCII. The cytG mutation may be useful in elucidating the sequence of events involved in the degradation of LHCII proteins and their associated pigments during senescence.
Histochemical and ultrastructural studies demonstrate that topical all-trans retinoic acid (RA) stimulates the deposition of a subepidermal band of collagen in photoaged hairless mice. The aim of this study was to examine the effect of RA treatment on collagen synthesis using biochemical and immunochemical techniques. Albino hairless mice were irradiated three times a week for 10 weeks with four minimal erythema doses of UVB from Westinghouse FS-40 bulbs. In the post-UV period, mice were either nontreated or treated with 0.05% RA or the ethanol-propylene glycol vehicle for up to 10 weeks. Antibodies against the aminopropeptide (AP) of type III procollagen were used in immunofluorescence microscopy and radioimmunoassay techniques. The AP of type III collagen is normally present throughout the dermis and in areas of active collagen synthesis (i.e., the dermal-epidermal junction). In this study, a similar distribution was seen in all untreated and vehicle-treated mice, and in mice treated with RA for 2, 4, and 6 weeks. However, increased staining, in a subepidermal band, was detected in the 8-week RA-treated skin. This region became intensely fluorescent to a depth of 100 mu in the 10-week RA-treated skins. As determined by radioimmunoassay, the content of the AP of type III procollagen increased twofold with 10-week RA treatment. Because the ratio of type I to type III collagens remained constant in treated and untreated skins, it is reasonable to assume that the content of type I collagen increased in proportion to type III collagen in RA-treated skins.