shukoor65/lab-rag-model huggingface dataset:
Characterization of syngeneic rat monoclonal antibodies to the HSN tumor using syngeneic monoclonal anti-idiotopic antibodies. Twelve syngeneic anti-idiotopic mAb (anti-idiotypic/idiotopic antibodies Ab2)) were prepared from CBH/Cbi rats immunized with one of three monoclonal anti-HSN antibodies (Ab1) (11/160, ALN/11/53, or ALN/16/53) specific for the HSN tumor. The sera of the rats used for hybridoma production and all of the monoclonal Ab2 specifically inhibited the binding to HSN of the immunizing Ab1 only. It is concluded that, in this completely syngeneic system, only the private idiotopes associated with the antibody-combining site were immunogenic. Analyses using Western blotting showed that the Ab2 bound to intact Ab1 and to isolated H chains where the intra-strand disulfide bonds remained intact. The Ab2 did not bind to L chains or to fully reduced H chains of the Ab1. It is concluded that the idiotopes expressed on the H chain were conformational. When a panel of 13 monoclonal Ab1 (including the three used for immunization) were tested for reactivity with the Ab2, three reacted specifically with their respective Ab2 and 8 gave no binding suggesting that each Ab1 had a distinct idiotypic specificity despite the fact that all the Ab1 competed with each other for binding to Ag. However, the two remaining Ab1 (ALN/9/94 and ALN/12/17) generated from different tumor-bearing rats, were found to possess the same idiotypic specificity as 11/160. A detailed analysis using seven Ab2 raised against 11/160 showed that while the idiotype of ALN/9/94 and 11/160 were very similar, that of ALN/12/17 showed some clear differences. These three Ab1 have been shown previously to bind a sequential epitope on the HSN Ag in Western blots and it is postulated that the common idiotype of these Ab1 reflects their recognition of a sequential epitope. This may also account for the relatively frequent occurrence in tumor bearer sera of antibodies with this Id.
Complications of the variable screw plate pedicle screw fixation. In this study, 124 consecutive cases of posterior spinal fusion with variable screw plate fixation were reviewed. In 33 patients (27%), 41 complications were identified. Urinary tract infection without sequelae developed in 13 patients. Dural tear occurred in seven patients and wound hematoma in five. Wound infection developed in three patients; one was subfascial requiring instrument and graft removal. Neurologic deficit developed in seven patients (6%), in five of whom the deficit was due to manipulation and reduction of neural elements. Two of the seven deficits were believed to be caused by misplaced pedicle screws. Variable screw plate fixation is a formidable procedure with a significant complications rate.
Antibody-fluorescein conjugates for photoimmunodiagnosis of human colon carcinoma in nude mice. To improve the detectability of tumors by light-induced fluorescence, the use of monoclonal antibodies (MoAb) as carriers of fluorescent molecules was studied. As a model for this approach, the biodistribution of an anticarcinoembryonic antigen (CEA) MoAb coupled to fluorescein was studied in mice bearing a human colon carcinoma xenograft. In vitro, such conjugates with fluorescein-MoAb molar ratios ranging from four to 19, doubly labeled with 125I, showed more than 82% binding to immobilized CEA. In vivo, conjugates with a fluorescein-MoAb molar ratio of ten or less resulted in a tumor uptake of more than 30% of the injected dose of radioactivity per gram tumor at 24 hours. Tumor to liver, kidney, and muscle ratios of 20, 30 and 72, respectively, were obtained 48 hours after injection of the 125I-MoAb-(fluorescein)10 conjugate. The highest fluorescence intensity was always obtained for the tumor with the anti-CEA MoAb conjugate; whereas in control mice injected with fluoresceinated control immunoglobulin G1, no detectable increase in tumor fluorescence was observed. To compare these results with a classically used dye, mice bearing the same xenografts received 60 micrograms of Photofrin II. The intensity of the fluorescence signal of the tumor with this amount of Photofrin II was eight times lower than that obtained after an injection of 442 ng of fluorescein coupled with 20 micrograms of MoAb, which gave an absolute amount of fluorescein localized in the tumor of up to 125 ng/g of tumor. These results illustrate the possibility of improving the specificity of in vivo tumor localization of dyes for laser-induced fluorescence photodetection and phototherapy by coupling them to MoAb directed against tumor markers.
Estimated prevalence of dementia among elderly black and white community residents. A stratified random sample of 83 black and 81 white community residents aged 65 years and older in a five-county area in the Piedmont region of North Carolina was evaluated for dementia, using the Diagnostic and Statistical Manual of Mental Disorders, Third Edition, and the National Institute of Neurological Disorders and Stroke--Alzheimer's Disease and Related Disorders Association criteria. Of 164 subjects, 26 were found to be demented, resulting in an estimated prevalence rate of dementia in the five-county area of 16% (95% confidence interval, 7.92 to 24.08) for blacks and 3.05% (95% confidence interval, 0 to 6.91) for whites. The estimated prevalence of dementia for white women (2.9%) was similar to that for white men (3.3%), but the rate for black women was distinctly higher than for black men (19.9% and 8.9%, respectively). Blacks were more likely than whites to have a history of stroke, hypertension, and other chronic disorders that might have contributed to the development of dementia. Apart from differences in rates of institutionalization, no other relevant factors were identified that might explain the difference in the prevalence of dementia in these black and white community residents.
John Caffey Award paper. Avascular necrosis: early MR imaging and histologic findings in a canine model. To examine the early MR and histologic changes of avascular necrosis, we surgically devascularized the distal femur of adult beagle dogs and performed short TR/short TE MR imaging and histologic examinations. MR showed increasing areas of low signal, and histologic examination showed changes of fat necrosis, inflammatory infiltrate, and fibrocytic and bony repair. These processes were divided into four stages. Stage 1 is seen in the first days after surgery and consists of homogeneous high signal on MR and only subtle histologic changes of early fat necrosis. Stage 2, seen by 7 days after surgery, shows linear low-signal areas within the high-signal marrow on MR and fat necrosis and an inflammatory infiltrate on histologic sections. Stage 3, seen by 16 days after surgery, shows patchy low signal occupying more of the marrow on MR with a fibrocytic infiltrate on histologic sections. Stage 4, seen by 23 days after surgery, shows a more homogeneous low and intermediate signal on MR and histologic findings of more organized fibrocytes and the onset of new bone formation. Using this model, we have proved that MR imaging can show marrow changes as soon as 1 week after the onset of avascular necrosis. Whereas MR imaging showed a progression of increasing areas of low signal, the histologic findings seen during this time were diverse, including inflammatory infiltration (a previously unreported finding), fat necrosis, and fibrocytic and osseous repair.
Low incidence of point mutation at codon 12 of K-ras proto-oncogene in squamous cell carcinoma of the upper aerodigestive tract. Forty-two cases of squamous cell carcinoma arising in the upper aerodigestive tract were examined to determine the incidence and type of point mutation in codon 12 of the c-K-ras gene by using the polymerase chain reaction and oligonucleotide hybridization techniques on DNA extracted from paraffin blocks. DNA sequencing, in addition, was performed in 4 cases. No point mutation was detected in codon 12 of c-K-ras in the 42 squamous cell carcinomas we examined. According to the results of DNA sequencing of 4 cases, codon 13 also revealed no point mutation. Thus, point mutational activation of codon 12 of c-K-ras oncogene is an uncommon event in human upper aerodigestive tract squamous cell carcinoma.
Destruction of tumour parenchyma in basal cell carcinoma by tumour-associated neutral proteases: a histochemical study. Proteolytic activity was demonstrated histochemically in frozen sections of basal cell carcinomas (BCCs). After incubation of tissue sections in 0.1 M phosphate buffer with 0.25 M NaCl the tumour epithelium was almost completely destroyed. The basal and squamous cell layers of the epidermis disintegrated to varying degrees, particularly where they were directly in contact with tumour epithelium. Serine and metalloprotease inhibitors diminished this tissue destruction. Iodoacetate enhanced tumour destruction, urea and potassium thiocyanate even more so. The high proteolytic activity of BCC demonstrated in this study may be an important factor in the proliferative, invasive and destructive behaviour of this tumour.
Selegiline (deprenyl) treatment and death of nigral neurons in Parkinson's disease. We studied the effect of selegiline (deprenyl) treatment on the number of Lewy bodies and neuron counts in the substantia nigra in patients with Parkinson's disease (PD). The number of medial nigral neurons was greater and the number of Lewy bodies fewer in those PD patients who had been treated with selegiline in combination with levodopa as compared with patients who had received levodopa alone. This suggests that selegiline treatment may retard the death of nigral neurons, but alternative explanations, such as the reduction of levodopa dosage in selegiline-treated patients, are possible.
Simultaneous measurement of all thrombosis parameters from native human blood: usefulness in monitoring efficacy and complications of thrombolytic therapy. The sequelae of thrombus formation, both by shear forces and by collagen fiber, the subsequent coagulation, and the dislodgement of thrombi (thrombolysis) were measured from a small volume of nonanticoagulated blood sample, by a new instrument. Addition of streptokinase (SK) or tissue-type plasminogen activator (rt-PA) to the blood sample eliminated the need for anticoagulation for thrombolysis measurement: clot lysis preceded and allowed thrombolysis to occur. The test revealed activation of platelets and coagulation by SK and rt-PA. Apart from this general trend, platelet reactivity in response to plasminogen activator showed great individual variation. Whether the greatly enhanced (42%) or prolonged hemostasis (13%), observed in different blood samples with rt-PA, could be used as a predictor of reocclusion or bleeding complications remains to be established. Thrombolysis did not occur in 12% of the samples tested. These thrombolysis models may be useful for developing new agents for the dissolution of platelet-rich thrombi. It is suggested that this technique be used for monitoring thrombolytic therapy.
Carcinoma arising within fibroadenomas of the breast. A clinicopathologic study of 105 patients. The authors report the clinicopathologic features of 105 carcinomas arising within fibroadenomas (FAs) of the breast. The mean age of the patients was 44 years. The presentation and gross characteristics of these tumors rarely differed from those of uncomplicated FAs. Carcinoma in situ (CIS) was the predominant type of malignancy (95%) found to arise in FAs, and lobular and ductal types occurred with equal frequency. Nine of ten FAs harboring an invasive carcinoma also contained CIS supporting the origin of the infiltrative component in the FAs. CIS within FAs was associated with in situ malignancy in surrounding breast tissue in 21% of cases. Age, fibroadenoma size, and type and extent of CIS were similar in patients with disease limited to the FA and in those with associated malignant disease in the remainder of the breast. Axillary nodal metastases were not detected. Sixty-three patients were observed for a mean period of 8.4 years. Only one of 26 patients with CIS within an FA who was treated conservatively developed an ipsilateral carcinoma. None of the 26 developed contralateral carcinoma; however, 3 of 23 with similar lesions, who were treated by mastectomy, did so. The contralateral carcinomas were invasive in two patients, one of whom died with distant metastases. Seven patients with FAs harboring lobular CIS underwent bilateral mastectomy. Their postoperative course was uneventful. None of seven patients with invasive carcinoma arising in an FA, two of whom were treated conservatively, succumbed to disease. However, one developed contralateral carcinoma. The authors recommend breast-conserving therapy for CIS arising in an FA.
A prostacyclin analog impairs the response to tissue-type plasminogen activator during coronary thrombolysis: evidence for a pharmacokinetic interaction. Inhibition of thromboxane (TX) A2 with aspirin enhances the response to coronary thrombolysis. However, experimental evidence suggests that platelet activation during coronary thrombolysis is mediated by a number of agonists, in addition to TXA2. As a consequence, greater benefit would be expected with antiplatelet agents that have a broader spectrum of activity. However, a recent clinical trial, combining tissue plasminogen activator (t-PA) with the prostacyclin analog, iloprost, did not detect such a benefit. To address the mechanism of this response, we compared the effect of iloprost, a stable analog of prostacyclin, with GR32191, a TXA2/prostaglandin endoperoxide receptor antagonist, on the response to i.v. t-PA in a closed chest, canine model of coronary thrombosis. GR32191 reduced the time to reperfusion by 47% (n = 6, P less than .05), consistent with a role for TXA2-mediated platelet activation in impairing thrombolysis. In contrast, iloprost increased the time to reperfusion by 50% (n = 5, P = NS) and in four of nine animals reperfusion failed to occur despite inhibition of platelet aggregation. In a separate series of experiments, steady-state plasma t-PA clearance increased by 38% (407 +/- 49 vs. 294 +/- 42 ml/min; n = 8, P less than .02) during infusion of iloprost and recovered after its withdrawal. This appeared to be a specific effect, as infusion of nitroglycerin at a dose which induced a similar fall in blood pressure altered neither the time to reperfusion nor plasma t-PA. Iloprost impairs the thrombolytic response to t-PA via an increase in the clearance of this agent.
Mucosal cell proliferation of the rectal stump in ulcerative colitis patients after ileorectal anastomosis. The proliferative activity and polyamine levels of the rectal epithelium in unoperated ulcerative colitis patients and in ulcerative colitis patients after total colectomy and ileorectal anastomosis were determined and compared with control subjects. Cell proliferation was evaluated in rectal biopsies by in vitro 3H thymidine incorporation by measuring the labeling index and the position of labeled cells along the crypt; polyamines were determined with a chromatographic method. In ulcerative colitis patients the labeling index was significantly increased, and labeled cells were shifted toward the upper part of the crypt when compared with controls. Ileorectal anastomosis patients showed a normalization of the labeling index and a distribution of labeled cells similar to controls. Polyamine levels were also increased in ulcerative colitis patients; in ileorectal anastomosis patients, the level of polyamines was decreased in respect to unoperated patients and return to normal values except for spermine. Because the increased proliferation and higher polyamine levels are related to increased colon cancer risk, our results confirm that ulcerative colitis is a risk factor for the development of carcinoma. Ileorectal anastomosis may reduce this risk through a normalization of mucosal cell proliferative activity and of some polyamine levels.
Thrombolytic therapy with streptokinase stimulates collagen breakdown. BACKGROUND. Plasmin is capable of degrading extracellular matrix components such as collagen in vitro. To evaluate the significance of this for in vivo conditions, we set out to study the effect of streptokinase, which acts by converting plasminogen to plasmin, on the serum concentrations of the amino-terminal propeptide of type III procollagen (PIIINP) and the carboxy-terminal propeptide of type I procollagen (PICP). METHODS AND RESULTS. Twenty-three patients with suspected acute myocardial infarction were included in the study; 17 of them received thrombolytic therapy, and six were treated conservatively. PIIINP and PICP were assayed with radioimmunoassays. Kinetics of creatine kinase-MB release were determined to differentiate reperfusers from nonreperfusers. Composite curves of creatine kinase-MB release were constructed for different patient subgroups. During streptokinase infusion the serum concentrations of PIIINP increased rapidly, with a maximum mean increase of 50% (from 2.2 +/- 0.2 to 3.3 +/- 0.3 micrograms/l) in 45 minutes. A similar increase was also observed in two patients who received thrombolytic therapy but did not subsequently develop any myocardial infarction determined on the basis of enzyme release. The relative increase in PIIINP during streptokinase treatment was higher in those acute myocardial infarction patients with probable reperfusion than those with nonprobable reperfusion. Corresponding changes in PIIINP were not seen in the control group. Two days later there was a second increase in serum PIIINP for both patient groups. This change coincided with a similar increase in PICP. CONCLUSIONS. We conclude that streptokinase, probably by activation of plasminogen to plasmin, stimulates the breakdown of type III collagen during thrombolytic therapy. This phenomenon may decrease the risk of rethrombosis of the affected artery if the exposed collagen is responsible for thrombosis formation, but it could also be involved in the development of hemorrhagic complications during thrombolytic therapy. The second increase in PIIINP levels probably indicates type III collagen synthesis of the infarcted area. This investigation represents a pilot study, and more studies on the effects of various thrombolytic agents on interstitial collagen metabolism are obviously needed.
Molecular basis of an autoantibody-associated restriction fragment length polymorphism that confers susceptibility to autoimmune diseases. Recently, combined serological and molecular studies of autoantibodies have revealed that these antibodies play an important role in the normal function of the immune system and in the development of the B cell repertoire. Accordingly, we hypothesized that a homozygous deletion of a critical autoantibody-associated Ig variable (V) gene may alter the immune system and thus predispose the host to autoimmune disorders. Initial experiments revealed several restriction fragment length polymorphisms (RFLP) of the Humhv3005 gene, that is likely to encode heavy chains of rheumatoid factors, and the closely related 1.9III gene. By probing EcoR1-digested DNA with the Humhv3005/P1 probe, we found that one of the four major hybridizing bands was missing in approximately 20% of patients with either rheumatoid arthritis or systemic lupus erythematosus, but only 2% of normal subjects. To delineate the genetic basis of this polymorphism, we have now employed the PCR to amplify and analyze hv3005, 1.9III, and homologous genes in individuals with characteristic RFLP genotypes. Our results indicate that the human Vh gene repertoire contains several hv3005- and 1.9III-like genes, and that a complete deletion of the hv3005-like genes is relatively restricted to a subset of autoimmune patients. These findings provide initial evidence for deletion of developmentally regulated autoreactive V genes in autoimmune diseases.
Antibiotic management of outpatients with endocarditis due to penicillin-susceptible streptococci. Thirty patients with endocarditis caused by penicillin-susceptible streptococci were enrolled in one of two groups in this study. Fifteen patients received ceftriaxone (2 g once daily) for 4 weeks; the other 15 received the same dosage of ceftriaxone for 2 weeks and then received oral amoxicillin (1 g four times a day) for 2 weeks. For the 27 patients treated predominantly as outpatients, 380 days of hospitalization were avoided. Clinical cure was achieved for all patients in both groups. We conclude that ceftriaxone, alone or followed by a course of amoxicillin, is an efficacious mode of treatment for infective endocarditis caused by penicillin-susceptible streptococci. Treatment with these agents can be administered predominantly on an outpatient basis.
Endoscopic pulsed dye laser lithotripsy of gallbladder calculi in vivo. We have evaluated the efficacy and safety of pulsed dye laser lithotripsy of gallbladder calculi using a percutaneous endoscopic technique in a porcine model. Fragmentation was readily achieved in vivo. Using a combination of laser lithotripsy and saline lavage, complete removal of all stone debris was feasible through a 24 F tract (N = 3). However, the degree of fragmentation required rendered removal through a smaller tract inefficient, a mean 53% of stone mass being retrievable through a 16 F tract (N = 11). Repeated laser activation at 1 mm from the gallbladder mucosa produced minimal injury, regardless of pulse energy. When the laser fiber was pressed against the mucosa, perforation of the gallbladder was possible at therapeutic pulse energy, but this did not lead to clinical sequelae. We conclude that the pulsed dye laser is a safe and effective means of fragmenting gallbladder calculi in vivo.
Temporal arteritis with normal erythrocyte sedimentation rate. The erythrocyte sedimentation rate (ESR) is used to differentiate temporal arteritis from other forms of headache in the elderly. Though temporal arteritis can occur with a normal ESR, this is not generally appreciated in primary care. The case reported here is a 74-year-old woman with biopsy-proven temporal arteritis; her ESR was 22 mm/hr. Of note, her hematocrit was more than 40 percent, a condition previously reported to be associated with temporal arteritis and a normal ESR. This discussion focuses on the diagnosis of temporal arteritis and its associated symptoms.
Giant neuroendocrine (Merkel cell) carcinoma of the skin. An 82-year-old woman had a dark red to purple tumor on the left buttock that had gradually enlarged during the last 5 years. Although routine histologic examination was not sufficient for diagnosis, neuroendocrine carcinoma was diagnosed by immunohistochemical and ultrastructural studies. Immunohistochemical-positive reactions to neurofilament, cytokeratin, neuron-specific enolase, and epithelial membrane antigen were noted. Electron microscopically, membrane-bound, dense core granules that yielded a positive uranaffin reaction and intermediate filaments in the perinuclear area were observed in the cytoplasm of most tumor cells. Desmosome-like structure between them was also found. Approximately 6 months after local excision, metastatic lesions developed in the regional lymph nodes and liver.