Biomedical subjects
Publications and source records attributed to T Gray.
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The ultrastructure of the osteocytes, osteoblasts, osteoclasts, haemopoietic and other connective tissue cells was examined in 27 biopsies from 22 patients with Paget's disease of bone. Electron microscopy showed characteristic nuclear and cytoplasmic inclusions in the osteoclasts of all of the 25 biopsies exhibiting histological evidence of Paget's disease. Such inclusions were absent from all the other types examined. The intranuclear inclusions consisted of stacked rows or complex whorls of tubular filaments with an individual filament diameter of 12-15 nm, often arranged in a paracrystalline array. The frequency of occurrence of inclusions in the osteoclasts and their individual nuclei measured quantitatively in 18 of the biopsies was related to the histological severity of the disease process. The similarity of the observed inclusions to those of paramyxovirus inclusion bodies (particularly measles) support the hypothesis that Paget's disease is a slow virus infection.
While Epstein-Barr viral (EBV) DNA is nearly always detectable in African Burkitt's lymphoma (BL), the relatively low frequency of BL in EBV-positive African children and the infrequent finding of EBV in American BL suggest that other cofactors may contribute to the malignant transformation. Among these possible cofactors are type C oncornaviruses. To evaluate this possibility, we screened the cellular DNA from 16 lymphomas (2 African, 14 American) and the DNA from 20 lymphoma-derived cell lines (4 African, 16 American) with a radiolabeled viral DNA probe from EBV and two oncornaviral probes (murine amphotropic 1504A virus and simian sarcoma virus). The radiolabeled EBV DNA probe hybridized with 18 of 36 tumor or cell line DNA's. Only 2 of 11 American BL tumors contained detectable EBV sequences. However, the cell lines derived from three EBV-negative tumors converted in vitro to EBV positivity, suggesting that some of the tumor cells could be infected with EBV. In contrast, none of the tumors or the cell lines derived therefrom hybridized with either the 1504A or the simian sarcoma virus probes, decreasing the likelihood that type C viruses are cofactors with EBV.
Lever pressing for food on a variable interval (2.5 min) schedule was challenged by pretreatment with a 1.0 mg/kg dose of the dopamine receptor blocker pimozide. Large decreases in response rate were recorded even during the first few minutes of the test session before the rats had received any reinforcement. Pimozide also caused extinction-like effects, but it was clear, from comparisons between pimozide-treated rats that were rewarded and pimozide-treated rats that were not rewarded, that the rewarding effects of food were not totally blocked. It is suggested that an important aspect of the pimozide-produced response decrement is its effect on the incentive motivational properties of food-associated apparatus cues known to be important in sustaining responding under extinction and partial reinforcement conditions.
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The clinical and histologic features of a malignant intramedullary lymphoma of the spinal cord are reported. The duration of the disease was 9 months and the course was similar to other malignant intramedullary cord tumors. The tumor was confined to the cervical segment of the cord and histologically was composed of lymphocytes and plasmacytoid histiocytes. Effective treatment depends on tissue diagnosis.
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The capacity of auditory pathways from the weak ear (ear with the suppressed score in a dichotic listening test) to transmit speech information to the cortical processing areas was examined on 10 patients with unilateral temporal-lobe lesions. Three lines of evidence were developed to suggest that auditory pathways from the weak ear and speech information presented to the weak ear are not completely suppressed during dichotic stimulation. Speech in the weak ear frequently interacts with competing speech information in the strong ear causing contrasting articulatory features from the two ears to be blended into a single response. Two models of unilateral central auditory deficits are discussed: ipsilateral-suppression and transmission-line.
We sought to determine how the status of the meniscus and articular cartilage observed at the time of anterior cruciate ligament reconstruction affects results at 5 to 15 years after surgery. Objective follow-up was obtained on 482 patients at a mean of 7.6 years after surgery. Subjective follow-up was obtained on 928 patients at a mean of 8.6 years after surgery. Patients with both menisci present had significantly better KT-1,000 arthrometer scores than did patients with any part of the medial or both menisci removed. Stepwise regression analyses determined that a partial or total medial or lateral meniscectomy and damaged articular cartilage significantly lowered the final subjective total score. Patients with both menisci present and normal articular cartilage had a mean subjective total score of 94, and 97% had normal or near normal radiographic ratings on a weightbearing 45 degrees posteroanterior radiographs. The overall International Knee Documentation Committee rating was normal or nearly normal for 204 of 235 patients (87%) with both menisci present, 52 of 74 patients (70%) with partial or total lateral meniscectomies, 71 of 113 patients (63%) with partial or total medial meniscectomies, and 36 of 60 patients (60%) with both menisci removed. We concluded that the long-term subjective and objective results of a successful anterior cruciate ligament reconstruction are affected by the status of the menisci and articular surface.
We sought to determine the long-term results of 1057 consecutive patients who underwent an anterior cruciate ligament reconstruction with an autogenous patellar tendon graft from 1987 through 1993 and who followed an accelerated rehabilitation program. The patients were followed prospectively and objective physical examination data were obtained on 806 patients at a mean of 4.0 years postoperatively. Subjective follow-up data were obtained on 948 patients at a mean of 4.4 years postoperatively. The mean final range of motion was 5 degree/0 degrees/140 degrees. The mean manual maximum KT-1000 arthrometer score was 2.0 +/- 1.5 mm. Isokinetic quadriceps muscle strength testing revealed a mean of 94% strength after acute reconstructions and 91% strength after chronic reconstructions. International Knee Documentation Committee evaluation after acute reconstruction rated 42% of knees as normal, 47% as near normal, 10% as abnormal, and 1% as severely abnormal. The same evaluation after chronic reconstruction rated 41% of knees as normal, 44% as near normal, 14% as abnormal, and 1% as severely abnormal. Radiographically, 94% of acute knees and 89% of chronic knees had no joint space narrowing. Subjective modified Noyes questionnaire results showed a mean score of 93.2 +/- 7.9 points. The mean time for patients to return to sport-specific activities was 6.2 weeks and to athletic competition at full capacity was 6.2 months postoperatively. In the long-term, patients exhibited full range of motion, excellent stability, good strength, and a return of full function in most cases.
The GORE-TEX (W. L. Gore & Associates, Flagstaff, Arizona) graft was used in humans for about 10 years starting in 1982. During that time thousands of these ligaments were inserted. In our hospital, 162 GORE-TEX cruciate reconstructions were performed between 1986 and 1993 using a standard over-the-top technique. Two of these patients developed inguinal lymphadenopathy secondary to GORE-TEX particulate materials from the ipsilateral knee joint. To our knowledge, this is the first paper describing the above-mentioned complication, which was established by histologic examination, including electron microscopy.
The retinoic acid (RA) and differentiation dependence of constitutive expression of the nitric oxide synthase (NOS) isoforms, iNOS, eNOS, and bNOS, was examined by reverse transcriptase polymerase chain recitation (RT-PCR) in cultured, normal, human, tracheobronchial epithelial (NHTBE) cells. In the presence of RA (RA+), early passage NHTBE cells grown in air-liquid interface (ALI) cultures undergo mucous differentiation; in the absence of RA (RA-), they undergo metaplastic squamous differentiation. Under both conditions the respective differentiated phenotype develops around day 10 of culture. We found that iNOS mRNA levels were much higher in RA+ cultures, expressing the mucous phenotype, than in RA- cultures, expressing the metaplastic squamous phenotype. In contrast, eNOS mRNA levels were much higher in RA- cultures than in RA+ cultures. Expression of bNOS was not significantly affected by the RA status. The pattern of expression of NOS isoforms was then studied during the course of development of the two cellular phenotypes. During the early stages of differentiation, expression of iNOS (RA+) and eNOS (RA-) was very low, indicating that the expression of these two isoforms was not only dependent on the presence or absence of RA, but also on the degree of differentiation. The differentiation dependence of bNOS mRNA was less obvious. Four days of RA treatment of RA- cultures, which reverses the squamous phenotype and restores mucous differentiation, induced iNOS expression in a concentration-dependent manner. eNOS expression was depressed by 10(-8) M RA, while bNOS mRNA levels were slightly reduced by 10(-6) M RA. No NOS proteins were detected in unstimulated RA+ and RA- cultures. iNOS protein was induced by cytokine treatment in RA+ cultures, in contrast to eNOS and bNOS protein levels, which were unaffected. Our studies show that constitutive expression of the NOS isoforms is differentially regulated and that iNOS and eNOS mRNA levels are dependent on the stage of mucous and squamous differentiation, respectively. bNOS expression was only marginally affected by the RA or differentiation status.
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