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D J Wilson

Publications and source records attributed to D J Wilson.

At least 217 records · Page 12Linked to original sources
PubMed1987

The effect of the zone of polarizing activity (ZPA) on the anterior half of the chick wing bud.

Removal of the posterior half of the chick wing bud between stages 17-22 results in failure of the anterior distal tissue to survive and differentiate. This observation has been interpreted in terms of a requirement by the anterior half of a factor supplied by the posterior half of the limb containing the zone of polarizing activity (ZPA). This relationship has been tested by grafting ZPA tissue to the posterior surface of the anterior half after posterior half removal. Grafts made proximally on the cut surface did not significantly improve survival and development, nor did the ZPA prevent the expansion of the cell death in the ANZ beyond its normal boundaries into the distal mesenchyme. However, when grafted distally the ZPA inhibited cell death in the apical mesenchyme and caused the anterior mesenchyme to change its normal prospective fate (radius and digit 2). In all these cases, in addition to digit 2, digit 3 and frequently also digit 4 differentiated. The anterior half went on to develop a full set of digits and zeugopod parts in almost 50% of cases, although no skeleton resulting from this regulation of the anterior half had totally size regulated. These results demonstrate a developmental 'rescue' effect by the ZPA, and further support the view that the ZPA has a central and unique function in normal limb bud development, controlling survival and differentiation of the mesenchyme along the anteroposterior axis.

Animals↗
PubMed1987

Diagnostic ultrasound in haemophilia.

Ultrasound examination has been recommended for the evaluation of acute haemorrhages into soft tissues or joints in haemophilic patients. We have reviewed the notes of all such patients admitted during one calendar year and find that in 47 separate admissions the ultrasound examination assisted management decisions on 27 occasions. The technique is described with an analysis of the ways in which ultrasound observations may influence the clinician.

Adult↗
PubMed1987

Microplication patterns on human buccal epithelia following radiotherapy: a scanning electron microscopic analysis.

Surface topographical detail in human buccal smears of normal and irradiated tissue have been studied with scanning electron microscopy. Cells collected by buccal smearing show patterns of microplicae and microvilli, although such detail is occasionally masked by mucus and to a lesser extent by debris and bacteria. Buccal smearing permits collection of numerous specimens with little discomfort to the patient, but requires caution in identification of superficial and deep cell layers and of upper and lower surfaces. The analysis of specimens derived in this way shows that variations in the pattern of surface microplicae reflect the radiotherapeutic regimes of the patients from which they were obtained. Straight parallel microplicae characteristic of normal control and pre-irradiated specimens were absent in specimens collected during early irradiation treatments (between 24-48 Gy), but instead were present as short discontinuous ridges and microvillous projections. At the highest levels of radiation treatment (54-60 Gy) cells exhibited small areas devoid of any surface projections in addition to a range of normal and early irradiated microplicae patterns. From these results it is suggested that the patterns of microplications and microvilli on cell surfaces can be used to obtain information on the state of the stratified squamous epithelium from which they come.

Epithelium↗
PubMed1986

Human oncogene-transfected tumor cells display differential susceptibility to lysis by lymphokine-activated killer cells (LAK) and natural killer cells.

NIH 3T3 tertiary transfectants containing the N-ras or c-Ha-ras oncogenes derived from human tumors were tested for susceptibility to lymphokine-activated killer (LAK) cell and natural killer (NK) cell lysis. N-ras tertiary transfectants contained a human acute lymphocytic leukemia-derived N-ras oncogene. C-Ha-ras transfectants contained either the position 61-activated form of the oncogene (45.342, 45.322, and 45.3B2) or the position 12-activated form (144-162). In 4 hr 51Cr release assays, seven of seven in vivo grown human oncogene transfected NIH 3T3 fibroblasts were lysed by murine LAK effectors, whereas six of seven were lysed by human LAK effectors. There was no difference in susceptibility to lysis between cells transfected with the N-ras oncogene, the position 61 activated c-Ha-ras oncogene, or the position 12 activated c-Ha-ras oncogene. Cultured NIH 3T3 fibroblasts, as well as in vitro and in vivo grown NIH 3T3 tertiary transfectants were resistant to lysis by murine NK effectors and were relatively resistant (4/6 were not lysed) to lysis by human NK effectors. We conclude that human oncogene-transfected tumors are susceptible to lysis by both murine and human LAK cells while being relatively resistant to lysis by murine and human NK cells. Different oncogenes or the same oncogene activated by different point mutations do not specifically determine susceptibility to lysis by LAK or NK. Also the presence of an activated oncogene does not appear to be sufficient for inducing susceptibility to these cytotoxic lymphocyte populations.

Adenocarcinoma↗
PubMed1986

Choroidal neovascularization.

Choroidal neovascularization is now considered to be a most important feature in the pathogenesis and treatment of a number of chorioretinal disorders. Since the recognition of its importance, choroidal neovascularization has been described in clinical and pathologic studies of a variety of different ophthalmologic conditions. We have summarized the diseases in which choroidal neovascularization occurs and have reviewed studies on the natural history, clinical findings, and therapy of choroidal neovascularization that provide the basis for the current management of this condition.

Aged↗
PubMed1986

Pancreatitis: an important cause of abdominal symptoms in patients on peritoneal dialysis.

In an eight-month period, four patients in our peritoneal dialysis program developed acute pancreatitis, an incidence significantly higher than that in our hemodialysis program. Diagnosis was difficult since the symptoms of pancreatitis were similar to those of peritoneal dialysis-associated peritonitis. Further difficulties in diagnosis were due to unreliability of serum amylase levels and "routine" ultrasound examinations in suggesting the presence of pancreatitis. Computerized tomography performed in three patients showed enlarged, edematous pancreata with large extrapancreatic fluid collections in all cases. Two patients died, one directly due to complications of pancreatitis. One patient was changed to hemodialysis and showed clinical and radiologic resolution of his pancreatitis. One patient remains on peritoneal dialysis but has now had four attacks of acute pancreatitis. No patient had classic risk factors for development of pancreatitis. Review of patient histories showed no common historical factors except for renal failure itself, peritoneal dialysis, peritonitis, catheter surgery, and hypoproteinemia. It is possible that metabolic abnormalities related to absorption of glucose and buffer from dialysate or absorption of a toxic substance present in dialysate, bags, or tubing can cause pancreatitis in patients on peritoneal dialysis. We feel that a diagnosis of pancreatitis should be considered when peritoneal dialysis patients present with abdominal pain, particularly if peritoneal fluid cultures are negative or if patients with positive cultures do not have prompt resolution of symptoms with appropriate antibiotic therapy.

Abdomen↗
PubMed1986

Interleukin-2 and lymphokine activated killer (LAK) cells in the treatment of malignant glioma: clinical and experimental studies.

The phenomenon of glioma killing by lymphokine activated killer cells (LAK) was studied. We demonstrate that LAK cells generated by culturing the lymphokine interleukin-2 (IL-2) with peripheral blood lymphocytes from brain tumour patients destroys autologous glioma. The rat 9L glioma model was used to show that LAK killing was tumour-selective as glioma but not syngeneic normal brain tissue was destroyed. The susceptibility of both human and 9L rat glioma to LAK cell killing was markedly diminished by pretreating glioma cells with trypsin or chymotrypsin, but was unaffected by pretreatment with neuraminidase, glycosidases, sodium periodate or hydrocortisone. These results suggest that the cell surface determinant on glioma cells responsible for its tumour selective lysis by LAK is a protein sensitive to trypsin and chymotrypsin. The tumour-selective killing of glioma by LAK in vitro prompted the initiation of a Phase I study in which ten patients with malignant glioma have been treated with direct intracerebral injection of IL-2 or LAK without evidence of systemic or brain toxicity.

Adult↗
PubMed1986

Development of avascularity during cartilage differentiation in the embryonic limb. An exclusion model.

The differentiation of cartilage and muscle in limb-bud mesenchyme has been interpreted by some investigators in terms of a vascular pre-pattern model. It has been argued that a pre-pattern of the early limb vasculature compartmentalises the mesenchyme into specific microenvironmental areas in which, depending on the oxygen tension and nutrient supply, cartilage or muscle will differentiate. However, recent analyses of the development and differentiation of blood vessels in limbs have shown that regional variations in vascularization develop co-incidentally with the earliest indication of cartilage formation or mesenchymal condensation. The simple model described in the present study suggests that the mechanical compression/tension forces generated by the condensing mesenchyme are sufficient to constrict and eventually close off the thin-walled undifferentiated vessels caught in the condensation foci, thus leading to the avascularity of cartilage rudiments. This view suggests that the vasculature has no major function in governing the pattern of cartilage differentiation.

Animals↗
PubMed1986

In vitro killing of human glioblastoma by interleukin-2-activated autologous lymphocytes.

Culture of peripheral blood lymphocytes (PBL) from brain-tumor patients with recombinant interleukin-2 (IL-2) results in the activation of lymphokine-activated killer cells (LAK) with the capacity to lyse autologous and allogeneic glioblastoma. In this study, PBL obtained from brain-tumor patients were cultured with or without IL-2 for 3 to 7 days and then tested for their ability to lyse target cells in a 4-hour chromium release cytotoxicity assay. The PBL were drawn 1 to 2 weeks following operative tumor debulking. Cells used as targets included fresh brain-tumor cells obtained at the time of craniotomy, fresh brain-tumor cells grown from 1 to 3 weeks in tissue culture, fresh autologous PBL, and allogeneic glioblastoma cells grown in tissue culture. Peripheral blood lymphocytes from brain-tumor patients that were cultured without IL-2 did not significantly lyse autologous or allogeneic glioblastoma. However, when these PBL were cultured with IL-2, LAK were generated which produced marked lysis of autologous as well as allogeneic tissue-culture glioblastoma in all of eight cases. Significant lysis of autologous fresh tumor by patient LAK was observed in four of five experiments. By contrast, patient LAK did not kill autologous normal PBL. The ability to generate LAK was not influenced by the patient's age, previous therapy, or the administration of steroids.

Adolescent↗
PubMed1986

Interleukin-2 and autologous lymphokine-activated killer cells in the treatment of malignant glioma. Preliminary report.

Nine patients with malignant glioma were treated with the lymphokine interleukin-2 (IL-2) or with lymphokine-activated killer (LAK) cells, and one patient received combination therapy with both LAK cells and IL-2. The LAK cells were generated by culturing recombinant IL-2 with peripheral blood lymphocytes obtained from brain-tumor patients. Escalating doses of LAK cells (10(8) to 10(10] or IL-2 (10(4) to 10(6) U) were administered intraoperatively by direct injection into the brain tissue surrounding the cavity left by debulking the tumor. There were no signs of systemic or neural toxicity following treatment. The selective killing of the tumor by LAK cells used for these treatments was demonstrated by a chromium release microcytotoxicity assay which showed in vitro the ability of the LAK cells to lyse glioma cells but not normal cells.

Adult↗
PubMed1986

Interleukin 2-activated cytotoxic lymphocytes in cancer therapy.

LAK are cytolytic lymphocytes with the unique capacity for killing NK-resistant fresh human tumor cells in short-term assays. LAK kill autologous as well as allogeneic tumors with complete cross-reactivity. Initial studies on the classification of LAK conclude that LAK are distinct from the classical NK and T lymphocyte systems, based on a number of criteria including surface phenotype, activation conditions, and a spectrum of susceptible target cells. LAK kill ras oncogene-transfected fibroblasts like they kill fresh tumors. As yet, the target cell determinant responsible for susceptibility to LAK lysis is unknown. Activation of LAK requires only IL 2 and is blocked by monoclonal antibodies to the IL 2 receptor. Because only IL 2 alone is sufficient for LAK activation, we have done in vitro testing to determine whether fresh PBL could be activated in the presence of tumor, as might be desirable in vivo. LAK were activated sufficiently to mediate significant destruction of fresh tumor. We also tested whether LAK could be maintained in the presence of large tumors, providing IL 2 was added. Again, results were positive, suggesting that LAK either recycle or are a self-renewing population that depend on IL 2 for continued functions. Because of these and other findings, we have initiated a clinical protocol to test whether LAK made from the PBL of patients with brain tumor could eliminate residual glioma tumor cells. Autologous LAK plus rIL 2 to maintain lytic ability are injected during surgery. Preclinical studies in a rat glioma model have shown this approach to be safe, and previous in vivo murine studies have concluded that LAK kill tumors in Winn-type lung colony formation tests (Kedar et al. 1982). Much work is needed before we can understand the LAK phenomenon and determine its usefulness in cancer therapy, as well as its inherent biologic role. We hope that this chapter will stimulate both interest and the basic research needed to realize LAK potential.

Animals↗
PubMed1986

Interleukin-2 or autologous lymphokine-activated killer cell treatment of malignant glioma: phase I trial.

In a Phase I study, recombinant interleukin-2 (IL-2) or autochthohous lymphokine-activated killer (LAK) cells were used to treat nine patients with malignant glioma. One patient received the combination of IL-2 and LAK cells. LAK cells were generated by culturing IL-2 with peripheral blood lymphocytes obtained from brain tumor patients. Escalating doses of LAK cells (10(8)-10(10) or recombinant IL-2 (10(4)-10(6) units) were administered by direct injection into the brain tissue surrounding the cavity left following operative tumor removal. There have been no signs of systemic or neurotoxicity following treatment. The tumor selective killing of the LAK cells used for these treatments was demonstrated by their ability to lyse glioma cells but not normal cells in vitro using a chromium release microcytotoxicity assay.

Adult↗
PubMed1986

Once-daily treatment of essential hypertension with captopril.

After a 4- to 6-week placebo lead-in period, 382 mild-to-moderate hypertensive patients with diastolic blood pressures remaining between 92 and 109 mmHg were randomized to double-blind treatment with captopril (50 mg q.d.) (94), captopril (50 mg b.i.d.) (97), captopril (50 mg q.d.) plus hydrochlorothiazide (97), and placebo (94). After 4 weeks the captopril dosage was doubled, whereas the hydrochlorothiazide dose remained at 25 mg for an additional 4 weeks. Response to treatment was evaluated by means of blood pressure determinations at the end of 4 and 8 weeks. All three active treatment regimens reduced diastolic blood pressure more than placebo did (p less than or equal to 0.01). Patients receiving captopril with diuretic had a greater decrease in pressure than those receiving captopril alone. The once-daily captopril regimen was as effective as the twice-daily regimen, although the latter employed double the daily dose. Increasing the captopril dosage during the second 4-week period resulted in a minimal addition reduction in blood pressure. Full 24-hour monitoring confirmed that the blood pressure was controlled by once-daily captopril therapy. Captopril given once daily, alone or in combination with hydrochlorothiazide, is efficacious treatment for patients with mild-to-moderate hypertension. The once-daily regimen should further enhance patient compliance.

Adolescent↗
PubMed1986

Labetalol by continuous intravenous infusion in severe hypertension.

This study documents our experience with labetalol administered by continuous intravenous infusion for severe hypertension. Infusions were performed in 14 hospitalized patients (15 infusions) with supine diastolic pressure greater than 125 mmHg or supine systolic pressure greater than 200 mmHg. Blood pressures were measured by intra-arterial recording or an Arteriosonde 1225 Doppler instrument standardized with a mercury sphygmomanometer. Patients initially received 2 mg/min continuous infusion; the infusion rate varied between 0.5 and 2.0 mg/min according to the protocol. The infusion was terminated when diastolic pressure decreased 30 mmHg or when 300 mg of the drug had been infused. Goal blood pressure was achieved in all but two infusions. Sedation was the most common adverse reaction, followed by nausea and diaphoresis. No patient required discontinuation or reduction in infusion rate secondary to side effects. We conclude that continuous intravenous infusion of labetalol offers an effective alternative to current parenteral therapy.

Adult↗
PubMed1986

The incidence of diuretic-induced hypokalemia in two distinct clinic settings.

We studied the incidence of diuretic-induced hypokalemia (DIH) in two diuretic-treated hypertensive populations. Thirty-seven patients with mild hypertension were treated with HCTZ and monitored over 6 months. Group 1 (21 patients) was treated with 25 mg HCTZ q.d. in a public hypertension clinic. Group 2 (16 patients) was treated with 50 mg HCTZ q.d. in a private-practice setting. Group 1 was predominantly nonwhite (76% vs. 31% [p less than 0.002]). Baseline serum potassium levels were lower in group 1 (3.93 vs. 4.42 mEq/L [p less than 0.001]). Equivalent reductions in blood pressure and serum potassium were observed in both groups. Contrary to expectations, DIH (serum potassium less than 3.5 mEq/L) developed in 52% of group 1 and 19% of group 2 (p = 0.037). Black females were especially at risk for DIH. The higher incidence of DIH in group 1 appears to be related to lower baseline serum potassium levels.

Adolescent↗