Biomedical subjects
Publications and source records attributed to J Goldstein.
Chylothorax is a rare complication of coronary artery by-pass grafting. We present two patients who developed a left chylothorax at one week and 14 days post-coronary artery by-pass grafting. In both cases an internal mammary artery graft was harvested. Nonoperative therapy, which included adequate pleural drainage and a low fat diet, lead to successful resolution of the chylous leak in each instance.
Chicken liver alpha-N-acetylgalactosaminidase (alpha AGA) specifically removes terminally alpha-linked alpha-N-acetylgalactosamine from oligosaccharide chains on the surface of group A erythrocytes. Here, we report the molecular cloning of a alpha AGA cDNA by both library screening and PCR amplification. The clone contains a 1.2-kb 3'-untranslated region and 1.2-kb coding region which encodes a 45-kDa protein. The protein was produced in bacteria and in rabbit reticulocyte lysate, and is specifically recognized on Western blot by an antibody raised against the purified chicken liver enzyme. Enzymatic activity was detected when alpha AGA was produced in Saccharomyces cerevisiae. The deduced amino acid sequence shows 80% homology with human alpha AGA and about 60% homology with alpha-galactosidases from a number of sources, indicating that these two families of exoglycosidases are evolutionarily related.
To develop procedures for the expression of Rh antigen-containing proteins, we prepared a previously cloned Rh cDNA by isolation from a human bone marrow library using polymerase chain reaction (PCR). The cDNA that encodes either Rh(E) or (e) antigens was inserted into a vector (pGEM7ZRh) and transcription/translation performed in a reticulocyte lysate system. This produced a major (32 Kd) and minor (30 Kd) protein band in the region of sodium dodecyl sulfate (SDS) gels where Rh proteins are known to migrate. These same two proteins were immunoprecipitated by a rabbit anti-Rh antibody preparation that reacts with all Rh proteins, confirming that Rh protein was expressed in this cell-free system. Transient expression of Rh protein in COS-1 cells was also accomplished using a transfection vector (pBC12BIPLRh) containing inserted Rh cDNA. COS-1 cells transfected with this vector also produced a 32-Kd protein band that formed an immune complex with rabbit anti-Rh, while cells transfected with the same vector minus the Rh cDNA insert did not yield any detectable Rh immune-complexed protein. This system should prove useful for studying the transport of Rh proteins within the cell and the expression of Rh antigenicity at the cell surface.
Rabbit polyclonal antibodies were raised against synthetic peptides corresponding to hydrophilic regions of the human Rhesus (Rh) IX cDNA-encoded polypeptide predicted to be extracellularly or intracellularly exposed in the topologic model of the Rh blood group protein. Four antibodies encompassing residues 33-45 (MPC1), 224-233 (MPC4), 390-404 (MPC6), and 408-416 (MPC8) were characterized and compared with a polyclonal anti-Rh protein obtained by immunization with purified Rh proteins. All antibodies had specificity for authentic Rh polypeptides and reacted on Western blot with Rh proteins immunoprecipitated with human monoclonal anti-RhD, -c, and -E. MPC1, but not the other antibodies, agglutinated all human erythrocytes except Rhnull and Rhmod cells, which either lack totally or are severely deficient in Rh proteins, respectively. Immunoblotting analysis with membrane proteins from common and rare variants showed that MPC1 and MPC8 reacted in Western blot with 32-Kd Rh polypeptides from all common red blood cells except those from Rhnull and Rhmod, indicating that peptide regions 33-45 and 408-416 may be common to several if not all Rh proteins, whatever the Rh blood group specificity. MPC4 reacted only with membrane preparations from cells carrying the E antigen, whereas MPC6 recognized preferentially the Rh proteins from E and Ee preparations, suggesting that the protein encoded by the RhIXb cDNA carries the E and/or e antigen(s). Immunoadsorption experiments using inside-out or right-side-out sealed vesicules from DccEE red blood cells as competing antigen showed that the MPC6 and MPC8 antibodies bound only to the cytoplasmic side of the erythrocyte membrane, thus providing evidence for the intracellular orientation of the C-terminal 27 residues of the Rh polypeptides. Attempts to transiently or stably express the Rh polypeptides. Attempts to transiently or stably express the Rh cDNA in eukaryotic cells were largely unsuccessful, suggesting that Rh antigen expression at the cell surface requires correct transport and/or folding of the Rh proteins, possibly as a complex with one-membrane proteins of the Rh cluster that are lacking in Rhnull cells.
The healing of fetal tibial bone after osteotomy with and without stable fixation has been reported previously. The present study was designed to evaluate fetal bone gap healing using a tibial ostectomy model in fetal sheep. Eighteen time-dated pregnant ewes (20 fetuses, 34 experimental hind limbs) underwent intrauterine surgery at 95 days gestation (term, 145 days). A titanium miniplate was applied to the anterior aspect of the tibia and a longitudinal length of bone approximately 1.5 times its diameter was removed and the incision closed. The pregnancies were then allowed to progress until the ewe was killed at postoperative weeks 1, 2, 4, or 7. Assessments at that time included evaluation of gross morphology, histologic and radiologic appearance, and collagen analysis and hydroxyproline determination of the tissue within and at the borders of the gap. At 7 weeks, seven of nine bone gap specimens exhibited radiographic and histologic evidence of union with woven and lamellar bone. Hydroxyproline concentrations gradually increased within the bone gap over the period of the study. At all intervals, type I collagen composed over 90% of the collagen within the healing bony gap. Histologically and biochemically, the process appears to be similar to postnatal bone healing, albeit occurring at an accelerated rate.
Open liver biopsy in a 34-year-old woman with hepatosplenomegaly showed small noncleaved cell lymphoma. Except for an enlarged spleen, there was no evidence of other sites of involvement. She was treated with combination chemotherapy and is alive and free of disease > 5 years after diagnosis. We believe this to be the first reported case in an adult of primary hepatic or hepatosplenic lymphoma of the small cleaved cell type with long-term disease-free survival.
The effectiveness of membranous bone grafting in craniofacial reconstruction is hindered by resorption. The aim of this study was to determine whether alterations of the recipient bed through tissue expansion affect membranous bone graft survival. Eighteen adult rabbits were divided into three groups. Group I rabbits (control) received fixed autologous membranous bone grafts to their snouts. Group II rabbits had self-inflating tissue expanders inserted over their nasal dorsum, inflation for 3 weeks, and then expander removal and placement of fixed autologous membranous bone grafts to their snouts. Group III rabbits varied from group II by delaying bone grafting until 2 weeks after expander removal. One animal from each group was killed at post-grafting days 15 and 45, the remainder at day 90. Results were assessed by volumetric, nondecalcified histologic, and stereologic analysis. Volumetrically, group I grafts demonstrated 82 percent survival, whereas group II demonstrated 101 percent (p = 0.029) and group III 94.5 percent (p = 0.21). Histologically, group I grafts exhibited greater loss (i.e., porosity and resorption) and less labeling activity. Groups II and III showed extensive evidence of trabecularization and incorporation at the graft-host interface. Stereologic measurements such as osteoid seam width (OSW) confirmed the greater survival and activity of groups II and III bone grafts. Group II OSW measured 12.4 microns, group III 12.0 microns, and group I 9.8 microns (p = 0.04). Stereology also demonstrated that groups II and III's OSW approached that of the recipient bed and contralateral zygoma, whereas group I did not (p = 0.029), suggesting an integration of the graft and host architectures.(ABSTRACT TRUNCATED AT 250 WORDS)
This study looked for evidence of distinctive smoking lifestyles among social classes. Data on smoking attitudes and behaviors were collected via interviews of a representative sample of residents of a major western Canadian city. Four indicators of social class position (based on two approaches to conceptualizing social class) were employed. Regardless of the indicator of class used, few attitudinal or behavioral differences between social classes were found. The results suggest that the multi-faceted approach to smoking prevention in Canada has fostered a general climate of opinion which is antagonistic to smoking. Sociological factors which can lead to misperceptions of the extent of social class differences in smoking are discussed.
Between 1961 and 1991, 23 patients (eight men and 15 women, with a mean age of 50 (range 25-72) years) with cardiac myxomas were managed at the Alfred Hospital, Prahran, Victoria, Australia. Symptoms of mitral valve obstruction were present in 13 patients and of systemic embolism in nine. In the patients, 21 myxomas were confined to the left atrium. In the other two patients, one myxoma was confined to the right atrium and the other was a dumb-bell-shaped biatrial myxoma. Most tumours were diagnosed with echocardiography. Removal was achieved via a median sternotomy and by entering the involved chamber. Those myxomas presenting with systemic embolism were always soft and friable, whereas those with obstructive symptoms were large and of variable consistency. There was one operative death early in the series. The 22 surviving patients have been assessed as functional class I of the New York Heart Association at follow-up, ranging from 2 months to 23 years (mean 9 years). There were no episodes of tumour recurrence. Excellent short, intermediate and long-term results can be achieved by excision of cardiac myxomas.
BACKGROUND: The ocular and visual manifestations of multiple sclerosis are varied. The most uncommon is sheathing of the veins, periphlebitis. METHODS: A 39-year-old white female presented with primary visual complaints of contrast problems on a computer terminal. The patient was lost to follow up for 4 years, however, upon return a clinical diagnosis of multiple sclerosis was confirmed. Six years after the initial presentation, ophthalmoscopic exam of both eyes revealed marked focal sheathing of the retinal veins in the periphery, and associated hemorrhages in the right eye. RESULTS: During follow-up, the left eye became further involved developing hemorrhages and a retinal hole, which was treated. The visual consequence of the multiple sclerosis as a result of further exacerbations were bilateral centrocecal scotomas and midly reduced visual acuity. CONCLUSIONS: Multiple sclerosis should be considered in the differential diagnosis of patients with retinal periphlebitis.
We have previously shown that the effects of various enzyme treatments on Rh antigen-containing polypeptides in situ could be monitored by an antibody preparation which recognizes only these polypeptides following Western blotting. We now have prepared antibodies that specifically react with either the N- or C-terminal ends of Rh-related proteins. Using all three, we have established that the C-terminus of Rh(D) polypeptide is at the cell surface, whereas its N-terminal domain is situated at the cytoplasmic side of the red blood cell membrane. Chymotrypsin digestion of ghosts derived from (-D-/-D-) cells that are devoid of Rh (C/c) and (E/e) antigens produces three major Rh(D)-related fragments: the 20-Kd fragment contains the molecule's C-terminal domain, the 17-Kd fragment its N-terminus, and the 13-Kd fragment neither. However, only the 17-Kd fragment forms an immune-complex with human polyclonal anti-D, indicating that it contains the Rh(D) antigenic domain. Other findings presented here provide further evidence for a unique folding of Rh(D) polypeptide within the cell membrane and suggest that Rh(C/c) and (E/e) polypeptides, when present, may form complexes with it.
Sumatriptan, a specific serotonin1-like receptor agonist, was studied in the acute treatment of migraine. Two hundred forty-two adult migraineurs participated in a randomized, double-blind study in which one dose of 1, 2, 3, 4, 6, or 8 mg of subcutaneous sumatriptan succinate was evaluated in sequential ascending fashion. At each dose level, a placebo group was included. Efficacy was defined as reduction of moderate or severe pain to mild or no pain, without the use of rescue medication. Headache relief rates showed an approximate dose-response relationship and at 1 hour were as follows: placebo, 24%; 1 mg, 43%; 2 mg, 57%; 3 mg, 57%; 4 mg, 50%; 6 mg, 73%; and 8 mg, 80%. Relief of nausea and improvement in clinical disability were also approximately dose related. Adverse events were dose related; the most common types were injection site reactions and tingling. The 6-mg dose was as effective as the 8-mg dose but was associated with fewer adverse effects and so is optimal.
Pseudoaneurysm formation involving the body of an aortocoronary saphenous vein graft is a rare event. True aneurysmal dilatation of the graft and anastomotic pseudoaneurysm formation occur more commonly. We present the case of a 73-year-old woman in whom a pseudoaneurysm communicating with the body of a posterior descending coronary artery saphenous vein graft developed, presumably after a postoperative sternal wound infection. The aneurysm was excised and the defect within the saphenous vein graft repaired using hypothermia and circulatory arrest.
Patients who are infected with the human immunodeficiency virus (HIV) may develop benign lymphoepithelial cysts within the parotid gland that cause severe facial deformity. Standard treatment for this disorder has been superficial parotidectomy, repeated fine-needle aspirations or observation alone. These approaches are unsatisfactory because elective surgery in immunocompromised patients should be avoided, the cysts recur soon after aspiration, and observation alone for a treatable deforming facial process is unacceptable. Radiotherapy's proven effectiveness in treating other benign disorders of the parotid gland led us to evaluate its usefulness as a treatment for this disorder. Eight patients with parotid enlargement, who were seropositive for HIV, received 8-10 Gy to the parotids in 1 week. Five patients had complete response and three patients had partial response. All were very satisfied with the cosmetic result. Treatment-related toxicity was well tolerated and consisted of mild xerostomia and transient taste loss. In all cases, these side effects resolved within 1 month. Radiation therapy thus appears to be an effective and well-tolerated treatment for AIDS-related parotid enlargement.
A patient with neurofibromatosis involving the small bowel who developed adenocarcinoma in an area of the ileum showing diffuse involvement of the disease is presented. Unlike the five cases with this association previously described, the present case shows a neuroendocrine component within the adenocarcinoma. The relation between neurofibromatosis of the bowel wall and adenocarcinoma may be explained by a decreased intestinal transit time in this patient. The presence of a carcinoid tumor in the ileum is not unusual in a patient with von Recklinghausen's disease, although the location of the carcinoid in the duodenum is described more frequently in these patients. The appearance of endocrine/neuroendocrine features within an adenocarcinoma already involved by diffuse neurofibromatosis is exceptional and may not be a chance event.
We describe a 40-year-old black North American woman with isolated hepatic tuberculosis and an incidentally elevated alkaline phosphatase. Imaging studies of the liver showed a lesion suggesting primary or metastatic disease, which turned out to be the so-called pseudotumoral form of hepatic tuberculosis. We believe this is the first case recorded in the English language literature of isolated hepatic tuberculosis manifesting first as an incidentally elevated alkaline phosphatase. It seems to be the third documented case in the English literature of a patient with this rare form of tuberculous involvement without systemic manifestations. The patient responded to antituberculous therapy and is healthy 4 years after treatment.
A case of pleomorphic lipoma is described. Pleomorphic lipoma is included in the "atypical" lipoma classification. Because of its atypical microscopic appearance, it must be differentiated from liposarcoma. We will discuss pleomorphic lipoma and its position in the classification of atypical fatty tumors.
The relative importance of type I and type II mechanisms in the photodynamic treatment of red blood cell concentrations (RBCC) to inactivate viruses was studied using aluminum phthalocyanine tetrasulfonate (AlPcS4), visible light and quenching or enhancing agents of reactive forms of oxygen. Treatment of a human RBCC with 10-13 microM AlPcS4 and 25-26 mW/cm2 visible light resulted in the rapid and complete inactivation of added vesicular stomatitis virus (VSV). The addition of mannitol, glycerol, reduced glutathione (GSH), or superoxide dismutase (SOD), known quenching agents of type I mechanisms, had little to no effect on the rate of inactivation of VSV. Significant inhibition of VSV kill was observed on addition of tryptophan or sodium azide, known quenchers of type II mechanisms. Additionally, the rate of VSV kill was enhanced in the presence of D2O. Taken together, these results indicate a predominant role of singlet oxygen in the inactivation of VSV on photodynamic treatment of RBCC. The relative importance of type I and type II mechanisms on cellular toxicity was also evaluated. Little, if any hemoglobin release was observed on treatment of human or rabbit RBCC with 10 microM AlPcS4 and 44 J/cm2 of visible light in the presence or absence of the above mentioned quenchers. The effect of the addition of quenchers on the recovery and circulatory survival of treated, autologous rabbit RBCC, labeled with 51Cr, was also assessed.(ABSTRACT TRUNCATED AT 250 WORDS)