Image resolution in the midsagittal plane of the Orthopantomograph-10 using Lanex regular and T-Mat G screen-film combination.

Image resolution was measured in the midsagittal plane of the Orthopantomograph-10 with the use of Lanex regular and T-Mat G screen-film combination. A thin platinum edge phantom was used to obtain images for calculation of the edge response functions. Subsequently, line spread functions and modulation transfer functions of the system were calculated. Noise equivalent passband values, which were expressed in line pairs per millimeter, were derived to describe the image resolution. The noise equivalent passband values derived in this study were generally smaller than those reported in a previous study. The width of the image layer was found to be uniform at different vertical levels.


Historical perspectives of chondromalacia patellae.

Widespread misuse of the term chondromalacia has led to confusion regarding its true meaning. This term should not be used to diagnose patellofemoral pain, but to describe lesions of articular cartilage. Recent advances using stereophotogrammetry to evaluate the patellofemoral joint and its articular cartilage may lead to new insight into the etiology of these lesions.


Imaging of the patellofemoral joint.

Abnormalities of the patellofemoral joint are one of the main problems in internal derangement of the knee. The role of different imaging modalities (plain radiographs, CT, CT/arthrograms, radionuclide scans, and MR imaging) is discussed in this article.


Conservative care for patellofemoral pain.

Patellofemoral pain is the most common presenting complaint about the knee joint. The explanation for this pain is not entirely clear. The four schools of thought concerning the etiology are divided among explanations based on anatomy, biomechanics, and biochemistry. The treatment for the disease is compromised by the lack of a clear causative agent. Exercises, braces, activity modification, and some medications form the basic protocol for treatment. Until the etiology becomes clear, these approaches represent the only reasonable therapy.


Rehabilitation of patellofemoral joint disorders.

Patellofemoral dysfunction may be one of the most common and troublesome maladies to affect a patient. The correct identification of the underlying causes is paramount. Once identified, an effective rehabilitation program should be implemented. The program should include stretching and strengthening as well as several other therapeutic modalities. The most successful rehabilitation program is designed to address the specific needs of the patient.


Patellofemoral pain in the pediatric patient.

The pediatric extensor mechanism is subject to a variety of congenital, developmental, and traumatic disorders. Growth related factors modulate the development of patellofemoral pathomechanics. Injuries to periarticular soft tissues, apophyseal, epiphyseal, and articular cartilage are identified by meticulous history and physical examination. Diagnostic radiographs and MR imaging are invaluable adjuncts. Specific rehabilitative programs are very effective and lead to a high degree of clinical success.


Arthroscopic evaluation and treatment of the patellofemoral joint.

Patellofemoral pain is a multifactorial problem. No single successful solution for problems related to the patellofemoral joint has been identified. One needs to consider the interaction of all of the factors affecting the extensor mechanism. Evaluation begins with a careful history, physical examination, and appropriate radiographic studies. Arthroscopy can provide additional information regarding the condition of the articular cartilage, patellar tracking, and the presence of other intra-articular lesions. Conservative treatment is the cornerstone of management and is effective in more than two-thirds of patients, making surgical treatment necessary in only a minority of instances. ALRR, although not an innocuous procedure, has an acceptably low complication rate and provides predictably good results when used in properly selected patients.


Arthroscopic lateral release and the lateral patellar compression syndrome.

An isolated arthroscopic lateral release can provide dramatic relief of anterior knee pain in a select group of patients. We believe this procedure is indicated for patients with lateral patellar compression syndrome without significant chondrosis who have not responded to nonoperative treatment. During the procedure, care must be taken to perform a complete release and to achieve hemostasis. The postoperative rehabilitation emphasizes control of swelling, patellar mobilization, and quadriceps strengthening. We strongly agree with Schonholtz et al who report that the "lateral retinacular release is not a minor procedure and should not be performed simply because it may help and it can't hurt."


The plica syndrome.

The plica syndrome is an uncommon pathologic entity diagnosed far too often in the setting of concomitant pathology. Medial patellar pain is more likely to be related to patellofemoral maltracking than to plica syndrome. Likewise, anteromedial joint line tenderness is more likely to be related to a meniscal tear than to a pathological plica. An accurate history and physical examination aided by appropriate ancillary tests to confirm the diagnosis are essential to avoid unnecessary surgical treatment. Conservative measures are very effective and must be emphasized before any operative procedure. When arthroscopy is indicated, a thorough examination of the entire knee joint is necessary. A plica may or may not be present. When a pathological plica is found, excision is rewarded with excellent results. Unfortunately, many normal plicae are removed simply because they are present and not because they are symptomatic or pathologic. This leads to persistent symptoms because of misdiagnosis, as well as possible complications secondary to the operation.


Surgical treatment for patellar instability.

The initial therapy for patellofemoral pain remains conservative. Once this treatment plan fails and examination has clearly identified the cause of the patellofemoral dysfunction, surgical treatment is considered. No single procedure corrects all patellofemoral problems, and the patient's age, the causative factor, the condition of the articular surface, and the level of activity should be considered. Surgical options include lateral retinacular release, proximal realignment, distal realignment, and proximal and distal realignment.


Distal realignment of the patellofemoral joint. Indications, effects, results, and recommendations.

Effective treatment of patellofemoral malalignment is possible with precise diagnosis. This precision must begin with a thorough history and physical examination. Both nonoperative and operative treatment are guided by the specific patterns identified. Distal realignment procedures including anteromedial tibial tubercle transfer necessitate meticulous surgical technique to achieve maximal benefit with a low rate of complications.


The Maquet osteotomy.

First proposed in 1963, the Maquet osteotomy can be used successfully for the treatment of selected patients with patellofemoral pain. A strict patient selection process must be used to achieve optimal clinical results. The complication rate can be limited, but not eliminated, by the use of meticulous surgical technique. Further prospective clinical studies, employing both subjective and objective evaluation methods, should be performed to optimize the interpretation of the clinical results.


Patellectomy.

We believe the patella should be preserved when possible and stress the significant use the patella has in normal knee function. Although alternative treatments can often be found, patellectomy may be indicated in selected patients to improve function and reduce pain.


Patellar resurfacing for patellofemoral arthritis.

Knee pain referable to the patellofemoral articulation is common in the general population. It remains a troubling problem for the orthopedic surgeon. Frequently, initial therapy, involving activity modification, anti-inflammatory medications, and isometric quadriceps strengthening, is successful in relieving symptoms. Surgical intervention is normally reserved for those patients with pain that is resistant to these modalities. Unfortunately, none of the various surgical options has proved to be totally dependable, durable, or reproducible. The results of isolated patellar and patellofemoral resurfacing procedures have been guarded. Patellar resurfacing appears to be most beneficial in younger patients with severe anterior knee pain. These individuals should be clearly warned that there is a relatively high likelihood that they will require additional surgical treatment or patellectomy at a later date. Fortunately, patellar resurfacing does not preclude patellectomy from being easily performed. Patellofemoral resurfacing, however, involves more overall involvement of the knee joint. This makes patellectomy less likely to be a successful salvage procedure. Despite our observations that knees with primary patellofemoral arthritis do not do as well after total knee replacement as those with tibio-femoral arthritis, this procedure remains the best treatment option. The durability and predictability of total knee arthroplasty are well documented. Its results far surpass those reported for isolated resurfacing procedures. With regard to patellar resurfacing as part of total knee arthroplasty, we recommend resurfacing all patellae. The literature, although not conclusive, lends support to this practice. Avoidance of metal-backed patellar components and special attention to technical details should decrease the complications associated with patellar resurfacing in future studies.(ABSTRACT TRUNCATED AT 250 WORDS)


The patella in total knee arthroplasty.

Controversy persists as to whether the patella should be resurfaced in total knee arthroplasty. Can the good results of patellar cartilage against the metal femoral component be expected to endure? Attention to technique can be expected to reduce some of the complications of resurfacing, notably fracture, rupture, and instability. Component breakage results from metal-backed designs, and the causes of patellar clunks have not been fully understood.


Disruptions of the extensor mechanism.

Extensor mechanism injuries represent a challenging problem for the orthopedic surgeon. Accurate diagnosis is essential because the best results are obtained with early diagnosis and treatment. Numerous techniques have been described for both early and late repairs. The choice of repair is dependent on the location of the tear, the time interval between injury and repair, and the degree of secondary contractures. Despite these difficulties, satisfactory results can be achieved.


Complications of patellofemoral joint surgery.

The goal of patellofemoral surgery, as is true in any surgical procedure, is the maximum benefit with the least morbidity. It is imperative that the surgeon be aware of the potential complications of operating on the patellofemoral joint. It was with this goal in mind that this review was undertaken. Complications specific to surgical therapy for LPCS, malalignment, degenerative arthritis, and trauma were covered. Procedure-specific complications were discussed, as well as IPCS and reflex sympathetic dystrophy. Recommendations on how to avoid these complications were made. Specific treatment recommendations, where appropriate, were also put forth.


[Management of congenital adrenal hyperplasia].

This review deals with the current problems in the management of classical 21-hydroxylase deficiency from the fetal life to the puberty. The clinical consequences of 21-hydroxylase deficiency reflect the disordered physiology--impaired secretion of glucocorticoids and mineralocorticoids, and excessive secretion of androgens. Current therapy is intended to correct the disordered physiology by replacing mineralocorticoid and glucocorticoid hormones, thereby reducing the ACTH-driven increase in adrenal androgen secretion. Treated patients should expect a normal life span and reproductive potential. This can be achieved by careful attention to regular measurements of clinical parameters and biochemical indices of control.


[Doppler echocardiography in the evaluation of left ventricular diastolic function in hypertension].

Twenty-five hypertensive patients were examined using Doppler echocardiography to determine the diastolic function of the left ventricle. Twenty-two parameters were analysed and the diastolic indexes were compared with the results of a control group of ten healthy volunteers. Patients with hypertension showed significant left ventricular hypertrophy with increased left ventricular mass and dilated left atrium. Eighty-five percent of the hypertensive patients were found to have impaired diastolic function. The peak velocity of the early, and late diastolic phase and also the duration of acceleration and deceleration are considered to be necessary in the investigation of the diastolic function of left ventricle. All the other parameters can be determined using the above mentioned ones. The late diastolic transmitral flow, the atrial filling velocity, the time of deceleration and acceleration and also the time velocity integral increased significantly. However, the early diastolic filling fraction decreased significantly. The abnormalities in left ventricular diastolic function and also the atrial enlargement may be the early signs of hypertensive heart disease and therefore have a great importance in the therapy.


[Diagnostic value of the determination of serum alpha2-HS-glycoprotein].

Opsonic glycoprotein, alpha 2-HS-glycoprotein concentration was studied in the serum of 753 patients with various hematological, malignant, immunological, metabolic, endocrine and liver diseases and 68 healthy controls. Decreased serum alpha 2-HS-glycoprotein levels were detected in patients with acute leukemias, chronic granulocyte and myelomonocyte leukemias, lymphomas, myelofibrosis, multiple myeloma, metastatizing solid tumors, systemic lupus erythematosus, rheumatoid arthritis, acute alcoholic hepatitis, fatty liver, chronic active hepatitis, liver cirrhosis, acute and chronic pancreatitis, and Crohn's disease. Elevated levels were measured in patients with B and NANB/C hepatitis. Further decreased levels were observed in some groups with secondary infections. Serum alpha 2-HS-glycoprotein levels are affected by many factors, influencing the synthesis and elimination of the protein. The detection of serum alpha 2-HS-glycoprotein concentration has no specific diagnostic value as a marker for tumors or other diseases, however, its determination can be useful for the assessment of a non-specific regulator of the host defence.


[Giant pigmented nevus associated with leptomeningeal melanocytosis].

A case of a thirteen-year old boy is reported with congenital pigmented nevi on the large part of the trunk and on the extremities. From his age of six generalised epileptiform convulsions were present. Owing to the suspicion of intracranial process he was examined with a negative result. He died of brain edema. On section cerebrospinal leptomeningeal melanocytosis was found beside the nevi. In addition to the clinical findings and treatment the morphological lesions are detailed too at macroscopic, microscopic and ultrastructural level discussing the possibility of the malignisation.


[5-year experience with BCG immunoprophylaxis in superficial bladder cancer].

Our 5-year experience with BCG in the tumor stage pTis, pTa and pT1, G I-II shows a lasting remission of 88.5% (73%) in 78 (26) patients treated with BCG preparation Pasteur (Connaught) after transurethral resection. A complete remission in patients with carcinoma in situ (12 patients) could be found in 92%. The local and systemic side-effects, which are of limited duration, are tolerable, well treatable and fully reversible.


[Changes in the activity of natural killer cells in superficial bladder cancer during intravesical BCG therapy].

Alteration of natural killer (NK) activity from the peripherial blood was examined in the patients with superficial bladder cancer during two years between 1989-1991. The natural killer cell activity in patients with superficial bladder cancer was significantly depressed that activity was found in normal controls (P less than 0.01). 23 patients received intravesical BCG immuntherapy and NK activity was detected in the same patients 72 times in different period during the therapy. The authors decided that the activity of NK cells alters in BCG therapy. Increase of NK cells activity in the most common way of this alteration but many different type of this change is possible. The lower dose BCG (120 mg) often induce augmentation of NK activity but high dose BCG (200 mg) more frequently caused depressed activity of NK cells. The authors didn't find direct connection between therapy effect and NK activity but they found significantly less NK activity (P less than 0.03) in the patients who are in relapse. According to their opinions the role of natural killer cells in the antitumor effect of BCG can not be excluded. They recommended more immunological investigations to clear up the anticancer effect of BCG immuntherapy.


[Rhabdomyoma of unusual manifestation].

According to our knowledge in adult pericardial effusion has never been reported to be present in cases of cardiac rhabdomyoma. We present the history of an adult patient with pericardial effusion due to cardiac rhabdomyoma.


[Clinical aspects and management of a retroperitoneal abscess].

14 patients with retroperitoneal abscess have been collected by the authors since June 1, 1988. The retroperitoneal abscess of multifactorial origin can be considered as a secondary disease. The physical clinical signs (e.g. psoas rigidity sign, palpable mass, costolumbal sensitivity) play central role in setting up of diagnosis, and these signs were present in more than 75% of the cases. The physical signs generally indicate advanced retroperitoneal abscess, and at the same time the contour of psoas muscle disappears and concavity of lumbal vertebras can be seen on plane abdominal X ray film. The exact diagnosis was achieved in mean 45 days after the on set of complaints, this fact urges, that the up-to-date imaging modalities (US, CT, NMR) should be applied earlier in septic conditions of unknown origin. Retroperitoneal surgical intervention was performed in their patients, in the future the percutaneous drainage procedure has to be considered as first intervention for retroperitoneal abscess. Retroperitoneal abscess secondary to malignant disease has unfavorable prognosis, 2 out of 14 patients with retroperitoneal abscess died, both of them had underlying malignancy.


[The role of ultrasound in the indication for surgery in acute scrotum].

Before the application of ultrasonography in the diagnosis of acute scrotum almost all cases were operated on, many unnecessarily. In the work presented here, we analyze surgical cases before and after the introduction of ultrasonography in our hospital. By the use of ultrasound, in the first year the number of operations and the number of non-justified operations were reduced to about the half and one fifth compared to corresponding data from earlier years.


[Determination of the cerebrovascular reserve capacity by using acetazolamide as well as transcranial Doppler and SPECT tests].

The aim of this study was the development of a simple bedside test to assess cerebrovascular reserve capacity using transcranial Doppler sonography. We tried to validate the increase in blood flow velocity as cerebrovascular reserve capacity in 20 (3 normal, 7 TIA, 10 completed stroke) patients. They were studied using transcranial Doppler sonography and rCBF SPECT before and after injection of 1 g acetazolamide. Their increases in blood flow velocity and changes in cerebral blood flow correlated significantly in the symptomatic hemispheres (p less than 0.001). Blood flow velocity between the two hemispheres (symptomatic and asymptomatic) was not significantly different at rest. We offer these simple and reliable methods in clinical studies to clarify the frequency of ischemic stroke of hemodynamic origin.


[Percutaneous balloon-catheter dilatation of benign strictures of the bile ducts].

Two cases of patients with benign biliary strictures (one with anastomotic and another with iatrogen stenosis of the common bile duct) successfully treated by percutaneous transhepatic balloon dilatation are presented. The patients have been symptom-free for 24 and 14 months, respectively. The author deals with the indication of the procedure including all the benign stenoses where surgical reconstruction is not feasible. It is also emphasized that the balloon dilatation needs rather long-time manipulation during which both the patient and the personnel are exposed to significant amount of scattered radiation. One of the important factors in decreasing the need for manipulation is the availability of adequate devices (a series of high pressure balloon catheters).


[Correlations between radionuclide first passage, hemodynamic and respiratory function parameters in cor pulmonale patients].

37 patients with chronic cor pulmonale have been investigated with radionuclide first passage, microcatheter-technique, respiratory function investigation, furthermore blood gas analysis. Significant positive correlation have been found between the pulmonary circulation time and the pulmonary artery pressure; between the pulmonary mean transit time and the pulmonary artery pressure; furthermore between the pulmonary stagnation index was calculated for the characterization of peripheral pulmonary stagnation and the pulmonary artery pressure. Significant negative correlation have been found between the pulmonary circulation time, the pulmonary mean transit time and the vital capacity, the FEV1, furthermore the O2-saturation values. The authors establish, that on the base of the close correlations between the isotopic circulation parameters and the clinical data, the radionuclide first passage investigation is suitable for the demonstration of the current conditions of cardiopulmonary circulation.


[Late results of intraoperative balloon dilatation in multilevel arterial diseases of the lower extremities].

Since 1981, 93 intraoperative balloon dilatation have been performed in 78 patients suffering from occlusive arterial disease of the lower extremities. 42 iliac dilations were performed on 34 patients, where 8 patients required dilatations at two sites, and 26 patients only at one site (common iliac artery: 15, external iliac artery: 27). 44 patients received femoro-popliteal dilations of which 7 patients required dilations at two sites, and 37 patients only at one site for a total of 51 dilations. The follow-up period ranged from 1 to 60 months with an accumulated patency rate of 92% in iliac and 39.3% in femoro-popliteal segment at 5 years. Fourteen patients died by the fifth year after intervention. Most of these deaths were due to concurrent cardiac disease. By improving inflow or outflow and reducing operative stress in poor risk patients balloon angioplasty is a valuable adjunct to vascular reconstruction.


[Detection of delta F508 mutation in cystic fibrosis].

The common major mutation (delta F508) resulting in the removal of a phenylalanine residue of the cystic fibrosis gene product has been identified in patients with cystic fibrosis in several European countries. The frequency of this mutation was analyzed in 39 Hungarian patients with cystic fibrosis and in some of their relatives. In 43 out of the total 65 persons involved in the study (66.15%), and in 50% of cystic fibrosis chromosomes the delta F508 mutation could be detected. 56.4% of the patients were homozygous for the mutation. The frequency of the delta F508 mutation in these Hungarian patients resembles the values found in Middle Europe. Pulmonary and enteral symptoms were more severe in cystic fibrosis patients with delta F508 mutation. Although the number of patients is relatively low, missing or mild lung involvement characterized the cases with non-delta F508 mutation.


[Simultaneous occurrence of persistent hematuria (thin basement membrane nephropathy) and light-chain proteinuria (benign monoclonal gammopathy) in a middle-aged male].

IgG lambda type of monoclonal gammopathy and thin basement membrane nephropathy were established in a middle-aged man examined because of persistent haematuria, lambda light-chain proteinuria and moderately diminished renal function. A 10% level of plasmocytosis was verified by bone-marrow aspiration. The more than 6-year follow-up showed the gammopathy to be benign. The thin basement membrane nephropathy was verified by electronmicroscopic analysis of renal tissue obtained by percutaneous renal biopsy: lamina densa of the glomerular capillaries thinned to 30-100 nm. In spite of the usually good outcome of thin basement membrane nephropathy, in this case it was accompanied by glomerular sclerosis, subsequent destruction of nephrons, hypertensive vascular alterations and a clinical deterioration of the renal function after 4 years. A rebiopsy excluded the possible complications (amyloidosis, non-amyloid immunoglobulin nephropathy, cylinder nephropathy, etc) of light-chain proteinuria.


[Incidence of hepatitis B, C and D infection in chronic liver diseases].

The authors tested hepatitis B (HBsAg, anti-HBs, anti-HBc, IgM anti-HBc, HBe, anti-HBe), C (anti-HCV) and D (anti-HD, IgM anti-HD) virus markers in the sera of 204 patients, who suffered from histologically confirmed chronic liver diseases (age: 18-72, average: 46.8 y) by Sorin Biomedica RIA and Abbott ELISA kits. On the basis of detailed virus serological tests, they obtained data indicating viral etiology in 62% of the cases. 33.3% of the patients were anti-HCV, 52.5% of the patients were HBV marker seropositive and 11.2% of the HBV seropositive cases were anti-HD seropositive. In 2% of the cases seropositivity of all the three viruses was proved. In 26% of the patients seropositivity of two viruses (HBV and HCV, or HBV and HDV) was proved. They observed severe, progressing liver diseases in patients with HBV, HCV and HDV marker seropositivity in a higher ratio than in seronegative patients. In the cases of combined virus marker seropositivity the incidence rate of chronic hepatitis and liver cirrhosis was higher than in only HBV marker seropositive patients, but did not differ significantly from those only anti-HCV seropositive. In the cases of fought-off HBV infection the severity of the liver disease was milder than in the cases of replication and integration stage. Anti-HD seropositivity occurred in all stages of HBV infection, but active HDV infection, in most of the cases, was observed only in cases in the integration stage. Anti-HCV seropositivity was observed mainly in the fought-off HBV infection stage. Their results suggest that HCV infection, like HDV infection, may suppress HBV replication.(ABSTRACT TRUNCATED AT 250 WORDS)


[Experience with hydrogen (H2) breath test].

The authors applied regularly the hydrogen (H2) breath test during the medical investigations in patients with gastrointestinal symptoms. On the basis of the repeated examinations the hydrogen (H2) breath test is a sensitive, well repeatable method. After analysing of 108 examinations the authors have observed in 51.8% lactose intolerance, in 17.8% small intestinal bacterial overgrowth syndrome, in 46.4% motility disorders. The proportion of "low hydrogen producers" was 14.3%. Only 1/5 of patients with new diagnosed lactose intolerance had knowledge about the intolerance, and 10% was asymptomatic. In case of small intestinal bacterial overgrowth syndrome the repeated hydrogen (H2) test may indicate the effectivity of applied antibiotic therapy. The mean orocaecal transit time was 99 minutes and the normal range was 66-132 minutes, counted on the basis of mean +/- 2 SD. The authors suggest that the results support the important role of hydrogen (H2) breath test in the modern gastroenterological diagnostics.


[The value of acetazolamide provocation combined with blood flow tests in the diagnosis of ischemic cerebrovascular diseases].

In 28 (3 normal, 11 TIA, 14 completed stroke) patients 99mTc-HMPAO rCBF SPECT studies were performed at rest and after acetazolamide administration. For the investigations, a one-day protocol (the stress study directly followed the rest investigation) was used. The reconstructed and normalized slices were evaluated visually and semiquantitatively with a side difference analysis method. In the group of TIA patients, the abnormal results of the rCBF investigations increased from 55% to 82% after acetazolamide provocation. The corresponding results in the completed stroke group were 80% and 87%. After acetazolamide stimulation, hypoperfusion appeared or become more pronounced in the majority of the TIA group patients in contrast with the completed stroke patients with an unchanged or decreased perfusion abnormality. The semiquantitative evaluation method was mostly effective in the TIA group, where predominantly a one-sided cerebrovascular disorder was suspected. It was concluded that the 99mTc-HMPAO studies allow demonstration of the acetazolamide-induced cerebral perfusion alterations, and this method can be useful in the diagnosis and management of cerebrovascular disorders.


[Wernicke encephalopathy in childhood osteosarcoma].

Two children with osteosarcoma are presented in whom Wernicke encephalopathy with vomiting occurred during the chemotherapy. One of the children died with symptoms of toxic cardiomyopathy. Autopsy revealed Wernicke encephalopathy. The other child had similar symptoms (ocular signs, ataxia, somnolence). Parenteral thiamine had been given and after this therapy the child recovered from the encephalopathy. The authors emphasize the importance of the recognition of this neurological disorder occurring rarely in childhood: it can be cured with parenteral thiamine. Without thiamine treatment this condition is lethal.


[The place of pancreas transplantation in therapy].

Insulin dependent diabetes mellitus is one of the most ravaging diseases of the civilised world mainly because of its secondary complications. Even the most careful exogenous insulin administration can neither maintain an entirely physiological glucose metabolism nor prevent the development of the late complications. Today pancreatic transplantation is the only therapy leading to total normalisation of glucose and lipid metabolism in type I diabetic patients. Beside the improvement of the life quality resulted by the independence of the insulin administration and of the dietary restrictions, secondary complications as nephropathy, retinopathy and neuropathy are positively influenced. Best results can be obtained with the simultaneous procedure, grafting kidney and pancreas from the same donor. In this case the grafted pancreas can also increase the patient survival rate and the kidney graft function rate comparing with the results of the kidney transplantation alone. In conclusion simultaneous pancreatic-kidney transplantation is clearly indicated for the treatment of type I diabetic patients with end-stage kidney disease.


[Urinary incontinence in pregnancy and puerperium].

In a study of 421 patients questioned in immediate post-partum the author observed a urinary incontinence during pregnancy in 30.6% of the cases, this figure is comparable to those found in literature. The post-partum incontinence was not observed when forceps, vacuum extraction or caesarean section have been used. The urinary disorders observed during post-partum regresses spontaneously in 68% of the cases. However, one can ask the question on whether it is not reveal a light pelvic alteration which could cumulate at each delivery, so it would be necessary to use a pelvic training.


[Noninvasive imaging of the proximal coronary arteries by transesophageal echocardiography].

Authors give an account of their experiences about the visualization of the proximal coronary arteries on the basis of the transesophageal echocardiographic examination of 45 patients. According to their observations the left main coronary artery, the bifurcation, the left anterior descending artery and the circumflex coronary artery were well visualized in 40 patients. With the help of pulsed Doppler-echocardiography the Doppler flow velocity spectrum of the coronary flow can be detected, which could be analysed in 25 patients. At the same time the visualization of the right coronary artery is less sensitive, valuable images could be detected only in 12 patients. The technique of the TEE visualization of the proximal coronary arteries is described. TEE seems to be a promising approach to the morphologic evaluation of the proximal coronary arteries and for functional pathophysiologic examinations of coronary blood-flow.


[Examination of the orbit using a non-ophthalmologic ultrasound equipment].

Ophthalmic examinations were performed for determining the suitability of seven different types of non-ophthalmic ultrasound equipments for ophthalmological purposes. According to the results, the instruments with probes of 5 MHz or higher frequency are appropriate for certain screening ophthalmological purposes in hospitals where ophthalmic ultrasound instrument is still missing. The possible indications are: approximate estimation of axial eye length for intraocular lens calculation, and visualization of gross intraocular and orbital diseases, such as retinal detachment, tumours, foreign bodies etc. In case of pathological result or in case of axial eye length different from the average value, the high resolution ophthalmological ultrasound examination is mandatory. The modern colour-coded Doppler ultrasound equipments were found suitable for the examination of the circulation of the eye and orbit.


[Idiopathic thrombocytopenia caused by varicella].

The authors deal with the case of a 6-year old girl in whom thrombocytopenia developed with haemorrhagic symptoms as a rare complication of varicella. They give a short review about the reasons and the etiology of idiopathic thrombocytopenic purpura, and deal with the mechanism of thrombocytopenia caused by varicella.


[Theoretical possibility of using gene therapy in malignant diseases].

The rapidly growing knowledge in molecular biology opened new methodological approaches, pharmacological targets, such as gene transfer or application of antisense oligomers. It is necessary to be familiar with the benefits and drawbacks of gene therapy to avoid the traps of unrealistic expectations and hopes, to solve moral and practical problems of gene manipulations and to find its proper values and rationals in the management of malignant tumors.


[Late complications of pancreatic injuries following blunt abdominal trauma].

In connection with three successfully operated cases authors are treating the types of late pancreatic complications after blunt abdominal trauma. It is emphasized that the preoperative diagnosis is difficult. Many times weeks or months pass away after the trauma without any symptoms and only developed complication can be noticed first. The importance of the first provision and the need for a careful examination of the pancreas at operation is underlined. In the case of the less suspicion of pancreatic injury they suggest wide, adequate drainage. At last they call attention to the responsibility of the surgeon making the first operation.


[The thinning of the glomerular basal membrane in IgA glomerulonephritis].

Ultrastructural changes of the glomerular basement membrane (GBM) in 34 patients with IgA nephritis and their possible correlation with the main clinical symptoms were examined. In 23 patients thinner than normal GBM segments were found with a mean thickness of 116-120 nm (measured by the method of Osawa). Often foot process fusion but neither disruption nor deposition of immune complexes was seen in the affected capillaries. All patients had hematuria, while those with thin GBM segments had more severe hematuria and more episodes of macrohematuria. Other clinical features were unrelated to ultrastructural changes. It is suggested that the thin GBM may be a predisposing factor to hematuria.


[A case of adult Gaucher disease].

The authors describe a case of an adult patient having Gaucher's disease, who had hepatosplenomegaly and pancytopenia. The diagnosis was established by the low level of leukocyte beta-glucosidase and by histology of bone marrow, liver and spleen. The patient had no bone pain, but MRI described characteristic lesions of the femur. Serum acid phosphatase was characteristically elevated. The hypersplenism was reduced after splenectomy. The patient has a daughter with central nervous system dysfunction. Her chromosome examination is normal, but she has lower leukocyte beta-glucosidase activity too. She may have a Gaucher's disease of type II, the acute neuropathic form.


[Prognostic value of cell proliferation markers in malignant tumor diseases].

Novel methods used in studying the proliferation activity and cell kinetics of malignant neoplasms such as: the in vivo and in vitro bromodeoxyuridine labeling, the flow cytometric DNS analysis, the immunohistochemical demonstration of the so called proliferation associated antigens and the counting of nucleolar organized regions are briefly introduced. The data obtainable by these methods are reviewed and critically discussed. The prognostic value of the obtained data and their utility in planning and monitoring of cancer patients' therapy are also discussed.


[Significant bacteriospermia. Value and limits of sperm count in andrology].

The data concerning bacteriospermia--are very different in the literature. Asymptomatic andrologic patients, and as control group--patients of the outpatient department for male adnexitis--were studied. Cultivation of aerobic bacteria and mycoplasmas has been recently accomplished by quantitative bacteriological analysis and chlamydia diagnostic. The microbiological screening of 210 andrologic patients ejaculate has given the following results: 19.6% were sterile, 21.0% were colonised by apathogens, 59.1% were positive: 6.2% Mycoplasma hominis, 15.8% Ureaplasma urealyticum, 13.3% Chlamydia trachomatis, 51.9% other aerobic pathogens. 27.6% of samples contained more then one kind of bacteria strains. Quantitative isolation of aerobics and mycoplasmas in both andrological and male adnexitis patients groups showed the following distribution. In the andrologic groups 14.7% of samples contained 10(4) CFU/ml, 9.6% more than 10(4) CFU/ml aerobic bacteria; in the male adnexitis group nearly twice higher values could be observed (20.2% and 19.5%). The distribution of mycoplasma CFU/ml was the following; andrologie group: 20.1% of samples contained 10(4) mycoplasma CFU/ml, 37.5% more than 10(4) CFU/ml; in the male adnixitis group the identical values: 22.9%, 66.9%. Chi 2 statistical analysis showed significant difference ((p = 0.000) in the distribution of data in the two groups. On the other hand both of the groups contained all kinds of bacteriological concentration and even negative cases. Therefore authors suggest more biochemical investigations for detecting inflammatory diseases. Spermaparameters (motility and progressive motility) of andrological patients, divided by sperm concentration (cell number above and under 20 million/ml) and the degree of infection (non infected, slightly infected, and above 10(4) CFU/ml) were significantly different in the seriously infected group by variance analysis (p = 0.000).


[Experience with using a myocutaneous flap, obtained from the gluteus maximus, in covering sacral decubitus wounds].

Nonsurgical treatment of pressure sores of the sacral region showed in long term poor results. After a short review of surgical procedures the method of gluteus maximus myocutaneous flaps is described. The results suggest that the method offers a well vascularised and resistant soft tissue cover of the pressure sore and it can be performed in any surgical department. Stay in hospital may decrease significantly and the hope for a complete rehabilitation increases.


[Cobalt-induced asthma in workers exposed to hard metal dust].

A case of 39 years old woman with asthma bronchiale associated with cobalt exposure is reported. Specific bronchial provocation tests in these patients supported the diagnosis of hard-metal-induced asthma and implicated cobalt as the agent responsible. The relevant literature data are reviewed.


[Shoulder arthroscopy in degenerative and inflammatory diseases].

A new concept of shoulder arthroscopy is presented based on experience with 800 shoulder arthroscopies. All open surgical procedure on the shoulder are preceded by arthroscopy. The procedure is performed with the patient lying on his or her side. The medium is CO2, and the advantages are less bleeding, a natural picture, no fluid edema. After diagnostic arthroscopy (with CO2), operative arthroscopy (with fluid) or open joint surgery follows. The surgery can easily be performed in the same position for good access with any approach. Preliminary diagnostic arthroscopy helps to plan the procedure (approach, additional surgery). Minimal exposure is beneficial for faster rehabilitation.


[Arthroscopy of the wrist and elbow joint].

Arthroscopy of the wrist and elbow is a helpful diagnostic procedure in patients with chronic disability not demonstrated by clinical and radiological examinations. At the wrist, especially triangular fibrocartilage, chondral or ligamentous defects can often not be demonstrated by other tests. Arthroscopy of the wrist allows examination of more than a dozen separate articular surfaces and the function of eight discrete joints. The geometry of the elbow joint limits intra-articular inspection and the use of instruments. The risk of neurovascular injuries is great and depends on exact puncture sites and portals. Its efficiacy is not yet proven.


[Current status of diagnostic and surgical hip arthroscopy].

Due to the anatomy and topography of the hip, clinical diagnostic procedures are often not very significant. Even the use of highly technical examination methods mostly does not allow differentiation of specific hip problems and do not give exact information about the extent and stage of the lesion. This applies specifically for rheumatoid diseases. Arthroscopy of the hip joint, like other big joints of the extremities, closes this diagnostic gap. Directly visualized findings on the joint, in addition to the results of joint aspiration and histological biopsies, give one security in finding the right diagnosis and planning adequate therapy. The conventional surgical approach to the hip joint leads to large wounds and to corresponding risks and damage to the patient. The advantages of arthroscopy are obvious. It was shown that arthroscopic surgery can be used very efficiently in cases with loose-body, osteochondrosis dissecans, scattered cartilage fragments, or septic arthritis. The other therapeutic application is in cases with rheumatoid arthritis where an arthroscopically assisted synovectomy to the hip achieves a high rate of success without temporary luxation. Diagnostic arthroscopy and arthroscopic surgery to the hip have been used in the Orthopedic Department of the University of Ulm since autumn of 1984. The possibilities and limitations of this surgical procedure have been evaluated in more than 100 cases. Based on our experience with arthroscopy on hip joints, we think that this procedure is very helpful for making a diagnosis and administering therapy.


[Diagnostic arthroscopy and arthroscopic surgery of the upper ankle joint].

Arthroscopy of the ankle joint was limited to the anterior compartments for a long time. The key to the entire diagnostic and therapeutic arthroscopy procedure on the ankle joint was the distension of the joint space through modern distraction techniques. The distraction devices available make arthroscopic surgery of the ankle joint as effective as in other joints like the knee and shoulder. Distension of the joint space allows visualization of all compartments, including the posterior ankle. In the case of hidden cartilage pathology of the posterior talus, an osteotomy linked with hardware removal through a second operation can be avoided today. The indications for arthroscopy of the ankle are pain, swelling, instability, hemarthrosis and joint locking. Generally, arthroscopy of the ankle joint is performed utilizing three general portals: anterolateral, anteromedial and posterolateral. Arthroscopic standard equipment, including the small joint set, is sufficient to treat the major part of ankle pathology through the standard portals. Arthroscopic ankle joint debridement in degenerative arthritis, removal of osteophytes, elimination of loose bodies and the management of soft tissue and bony impingement are possible. A complete synovectomy can be performed, including the posterior compartments. The treatment of osteochondritis dissecans is facilitated through the transmalleolar approach in combination with the distraction device. Arthroscopic ankle arthrodesis is possible and induces less trauma because an arthrotomy can be avoided. In our opinion diagnostic arthroscopy and arthroscopic surgery of the ankle joint is a procedure of great benefit for the patients if the indications are strictly adherred to.


[Endoscopy of the spine: minimally invasive therapy].

Since 1982 discoscopy has proved its value as a mean of continuous optic control of percutaneous intradiscal procedures. Thus, precisely oriented removal of disc tissue became possible for posterior decompression. Since 1989, discoscopy has opened the way for optically controlled intradiscal laser application. Besides decompressive procedures, since 1988 specific elaboration of the vertebral plates for percutaneous interbody fusion has also become available under discoscopic control. A most promising prospect is the technique of foraminoscopy introduced in 1991, which also opened the way to extradiscal exploration. The further development of versatile fine working scopes will be a bigger and bigger challenge to conventional techniques, as the concept of minimal intervention in spine surgery becomes more and more complete.


[Use of lasers in arthroscopy].

Arthroscopic surgery has become a routine procedure, thanks to the availability of excellent video systems and the development of new and efficient instruments. Since early 1980 several groups have been developing arthroscopic laser surgery. Laser technology is ideal for use in endoscopic surgery because lasers are potentially extremely small but nevertheless powerful tools with many advantages. Initially, attempts were made to modify CO2 lasers an Nd: YAG lasers for arthroscopic surgery, since these devices were readily available in many hospitals, but they proved unsuitable for arthroscopy. Clear definition of the desired goals and much experimentation eventually led to the development of three suitable systems: excimer, holmium: YAG and erbium: YAG lasers. After extensive investigation in the past few years, many groups have, for technical reasons, now opted for the holmium: YAG-laser as the best compromise. Lasers are used in arthroscopy not only to divide tissue but also to smoothen cartilage, for hemostasis, for percutaneous lumbar and cervical disc surgery, for photodynamic therapy, for tumor therapy and in diagnosis. The threshold to clinical practice in orthopedic laser surgery has now been crossed. Lasers must now show, in prospective clinical studies, that their theoretical advantages are matched in practice.


[Treatment of deformities of the locomotor system in hemiplegia].

In spastic hemiplegia mainly one side of the body is affected. In both the upper and the lower extremity the distal parts (hand and foot) are more severely involved than the proximal region. In cases of minor involvement the goal of treatment in the upper extremity is to achieve functional improvement by means of splinting and surgery. In cases of severe alterations cosmetic improvement without much functional gain is all that can be expected. Gait analysis has demonstrated that there are four basic patterns that can be related to the severity of involvement. In type I muscle imbalance exists without a contracture. In type II there is contracture of the muscles of the posterior compartment of the calf. In type III, in addition to the changes around the ankle joint, contractures around the knee are present, and in type IV also hip problems. Functional improvement can be achieved by means of splinting and surgery in all types. Basic principles of treatment have developed as a result of the application of gait analysis and dynamic electromyography. Specific examples of such treatment principles have recently been presented by Gage.


[Surgical treatment concepts of deformities of the upper extremities in infantile cerebral palsy].

To correct the most frequent deformity of the spastic hand, muscle release and transfer operations, such as distal slide of hand and finger flexors (according to Scaglietti and Göb), release of the adductor pollicis and flexor pollicis brevis muscle (Matev), and transposition of the flexor carpi ulnaris muscle to the dorsal aspect of the hand, should be performed. These basic operations on the spastic hand can be supplemented by release or transposition of additional muscles of the fingers or hand. Bony procedures should be done to stabilize and augment the grip between thumb and second finger. In selected cases arthrodesis of the wrist can be performed to stabilize the hand in a functional position. The outcome of operations on the spastic hand depends on the application of correct indications as well as on postoperative physiotherapy. A slight functional gain, or even a purely cosmetic improvement, may mean a lot to the patient. In respect of professional rehabilitation of adolescents, operative correction of a deformed hand can help to improve manual skills and thereby increase job chances.


[Spinal disorders in cerebral palsy--surgical procedure].

The incidence of scoliosis in cerebral palsy is related to the severity of the neurological involvement, being most prevalent in patients with spastic quadriplegia. Neuromuscular spinal deformity, when present, may progress after cessation of skeletal growth, and the success of orthotic treatment for scoliosis is unpredictable. Hip pathology is directly related to pelvic obliquity but has no causal relationship to the development of scoliosis. Adequate preoperative nutritional assessment is vital to reduce perioperative complications, and segmental spinal fixation is the instrumentation of choice. Anterior arthrodesis is indicated for rigid deformities and for those thoracolumbar and lumbar curves extending into the pelvis with pelvic obliquity and spinal decompensation.


[The hip in infantile cerebral palsy, natural developmental course and treatment concepts].

Classification of cerebral palsy according to the topographical distribution of clinical phenomena permits determination of a prognosis of the natural history of CP and the probability of hip problems to some extent. In 55 patients with CP, 101 muscle release operations were performed between 1971 and 1988. Preoperatively, the diagnosis was established by the neuropediatrician, function was evaluated according to the Rancho-los-amigos system, and the X-rays of the hip were assessed according to Reimers. For the postoperative evaluation patients were grouped according to neurologic diagnosis: hemiplegia (4), diplegia (19), total body involvement (31). Patients with hemiplegia had no functional or radiological changes as a result of the operation. In diplegia functional deterioration was seen in 4 cases (21%); in 3 cases (16%) this meant loss of the ability to walk. The migration percentage was improved from 48% to 39% on average. In 19 cerebral palsy patients with total body involvement surgery was considered to be indicated on the basis of a suspected dislocation of the hip. No functional changes occurred as a result of surgery. Hip dislocation was successfully prevented in 90% of the cases. The migration percentage was improved from 73% to 33%. In another 12 patients with total body involvement, adductor and iliopsoas release was performed to allow better hygiene and care and for pain relief. These goals were achieved; neither the Rancho-Los-Amigos function classification system nor X-rays were used to evaluate the results.


[Treatment concepts in knee malposition within the scope of primary neurologic diseases].

Disease and trauma to the central and peripheral nervous system can result in various disturbances to the stability and mobility of the knee joint. The aims of orthopaedic treatment in flaccid paralysis, spasticity, rigidity, athetosis and ataxia are discussed. The effect on the musculo-skeletal system is most severe when the damage occurs prenatally. The tendency to deformity in perinatal cerebral spastic disorders of movement can be considerably reduced by early systematic functional treatment. Active and passive exercise, corrective and reflex inhibiting casts and orthoses have proved their value in the prevention and treatment of muscle contractures in flaccid paralysis and spasticity. The dangers of treatment, such as subluxation of the knee and hip joint, osteoporotic fractures, and traction paralysis, must be taken into account. Muscle contractures often hinder function, both in spasticity and in flaccid paralysis, more than the underlying disease. The operative treatment of flexion contractures and impaired knee flexion in the swing phase of the step is discussed. Gait analysis facilitates the planning of treatment. The hip, knee and ankle joints must be treated as a single functional unit.


[Treatment of spastic club foot].

In 38 patients with spastic cerebral palsy, treatment was carried out for talipes equinovarus. There were 12 children with spastic hemiplegia, while 24 had diplegia or tetraplegia. Surgery was done with the goal of achieving plantigrade and muscle-balanced feet. In 24 feet of 19 children tibialis anterior transfer was performed, while tibialis posterior transfer was done in 20 feet of 19 patients. Without exception, additional surgery was performed on the triceps surae (30 x ATLs and 16 Vulpius operations); medial arthrolysis was also necessary in 6 cases. The clinical results were assessed by the senior author in the weekly neuro-orthopedic clinic an average of 3.2 years after surgery. An additional questionnaire was sent to all patients' families asking for their subjective assessment of the surgery performed. Figures were collected for 30 patients with 38 treated feet. The results were evaluated according to Kling's criteria. We saw good and very good results in 75% of the patients (4 feet very good, 23 feet good), while 25% of the patients (9 feet in 7 patients) showed poor results with over-corrections and calcaneo-valgus foot as the main problem. The best results were seen in spastic hemiplegia and the poorest in patients with severe tetraplegia and total body involvement.


[Treatment concepts of tertiary damage of the locomotor system after craniocerebral trauma].

Brain injuries are the most frequent cause of handicap in young adults. The success of rehabilitation depends mainly on the avoidance of tertiary lesions of the locomotor system. Between January 1989 and December 1991, 54 patients were treated at the neuro-rehabilitation unit of the Neurology Department of the University Hospital for severe brain injuries. On admission these patients were in different stages of recovery. All patients underwent physiotherapy adapted to their specific needs. The decision as to whether other kinds of treatment were indicated depended on the patients' problems in the recovery phase reached and on the presence or absence of tertiary lesions. In 14 patients, contractures caused by spasticity were successfully treated with plaster casts, which were changed weekly. These contractures were corrected sufficiently. In 5 other patients contractures, also caused by spasticity, were treated with regional anaesthesia administered through an implanted catheter system. In 11 patients a system for continuous intrathecal administration of Baclofen was implanted. Central side effects could be avoided while a lasting decrease of spasticity and hyper-reflexia was achieved. Persisting tertiary lesions, such as contractures, dislocations and spinal deformities, were corrected surgically.


[Peri-articular calcinosis after craniocerebral trauma--the natural course and treatment concepts].

Occurrence of periarticular ossification (PAO) is a serious complication in the rehabilitation of patients with neurological diseases, especially those with severe head injuries. The present concept for operative intervention in PAO postulates late surgical treatment after "maturation" of these heterotopic ossifications, because of a suspected higher rate of reoccurrence after early removal. In a retrospective analysis of nine arthrolysis in six patients with neurological diseases suffering from PAO (five patients with traumatic apallic syndrome and one patient with spontaneous subarachnoidal haemorrhage), the validity of a new concept of treatment of primary neurological diseases was investigated. Because of the well-known secondary and tertiary problems (fibrotic stiffness, osteoporosis, compression syndrome of peripheral nerves, muscle atrophy), we chose early removal of the ossifications. Our results demonstrate that the former concept of surgical intervention in "mature PAO" only can no longer be recommended as superior to early surgical treatment in neurological diseases, particularly in patients with traumatic apallic syndrome associated with PAO.


Association of Fyn with the activated platelet-derived growth factor receptor: requirements for binding and phosphorylation.

Three members of the Src family of tyrosine kinases [pp60c-src (Src), p59fyn (Fyn) and pp62c-yes (Yes)] are ubiquitously expressed, and are thus likely to have general roles in growth control. We have previously shown that, after addition of platelet-derived growth factor (PDGF) to quiescent cells, all three kinases become activated and associated with the PDGF receptor. We have now addressed the requirements for this association. First, we have used a baculovirus expression system to show that Fyn associates with the activated PDGF receptor in vitro in the absence of other proteins, demonstrating that the association between the two molecules is direct. Second, by generating cell lines expressing chimeric molecules consisting of Fyn sequences fused to a portion of beta-galactosidase, we found that the SH2 domain of Fyn is necessary for ligand-stimulated association with the PDGF receptor in vivo. Third, those fusion proteins that associated with the PDGF receptor also became phosphorylated in vivo following PDGF treatment, and in in vitro kinase assays, suggesting that the amino-terminal half of Fyn contains the sites of PDGF-stimulated phosphorylation. Partially purified, kinase-negative Fyn also became phosphorylated in the activated PDGF receptor complex in vitro, demonstrating that the PDGF receptor phosphorylates Fyn, rather than the novel phosphorylations occurring by autophosphorylation.


The v-ski oncogene cooperates with the v-sea oncogene in erythroid transformation by blocking erythroid differentiation.

The avian retrovirus oncogene v-ski was analysed for its ability to alter the differentiation program of erythroid cells and to cooperate with tyrosine kinase oncogenes in leukemogenesis. For this, a retrovirus combining v-ski with a temperature-sensitive version of the v-sea oncogene was constructed. In transformed erythroblasts, v-ski disturbed the concerted expression of several erythrocyte genes, leading to an abnormal erythroblast phenotype. Expression levels of hemoglobin and erythrocyte anion transporter (band 3) were elevated, while expression of the erythroid-specific histone H5 was strongly suppressed. v-ski could also be shown to repress or severely retard the temperature-induced erythroid differentiation of v-ski/ts-v-sea-transformed cells. The undifferentiated cells had an abnormal erythroblast or early reticulocyte phenotype characterized by unusually low levels of histone H5. In chicks, the v-ski/ts-v-sea virus displayed enhanced leukemogenicity compared with viruses containing just the single oncogenes. Thus, v-ski cooperates with tyrosine kinase oncogenes in a similar fashion to the v-erbA oncogene, however the pattern of genes affected by these two oncogenes is different.


Specific and complex interactions of murine p53 with DNA.

Biologically active mutant p53 from Balb/c mouse tumor cells (Meth A) was analysed for its specific interaction with DNA. Restricted phage lambda DNA, representing DNA of high complexity with regard to sequence and secondary structure, was used to probe for such an activity in a target-bound DNA-binding assay, using doubly immunopurified p53. A single lambda DNA fragment was specifically retained with very high affinity (KD = 10(-10) M). Specific DNA binding was shown to be an intrinsic property of p53, as it could be blocked with p53-specific monoclonal antibodies PAb122 and PAb421. The characteristics of the DNA binding of p53 to this lambda DNA fragment, as well as the structural properties of this fragment, suggested the possibility that p53 might be able to interact with nuclear matrix attachment region (MAR) DNA. Indeed, established genomic MAR elements were specifically bound by Meth A p53, whereas no binding was observed to an AT-rich control DNA. The interaction of p53 with MAR elements in vitro is compatible with the idea that p53 in vivo is involved in the regulation of replication and/or expression of cellular DNA. Complex DNA interactions were not restricted to mutant p53 from Meth A cells. Mutant p53 of a different conformational phenotype (PAb246+ 'wild-type' as opposed to PAb246- 'mutant' for p53 from Meth A cells) from minimally transformed T3T3 cells, as well as genotypic wild-type p53 expressed by a recombinant baculovirus in insect cells, exhibited similar DNA-binding properties.


Analysis of temperature-sensitive functions of Fos: lack of a correlation between transformation and TRE-dependent trans-activation.

We have identified and characterized a mutant v-Fos protein (DN16G) that is temperature sensitive for transformation. This protein contains an asparagine to glycine substitution at position 156 in the basic region encompassing the DNA contact site. This point mutation also strongly decreases trans-activation in a transient expression assay, using the collagenase 12-O-tetradecanoyl phorbol 13-acetate (TPA)-responsive element (TRE) as the target element. However, the apparent correlation between trans-activation and transformation does not hold in view of the observation that under certain temperature conditions (DN16G at 39.5 degrees C and E300 at 37 degrees C) both proteins showed similarly poor transactivation properties, but dramatically differed in their transforming potential. These findings clearly suggest that the activation of transcription via TREs as analysed in this study is not a crucial mechanism in Fos-induced transformation.


Cloning and developmental expression in Xenopus laevis of seven additional members of the Wnt family.

Degenerate oligonucleotide primers encoding highly conserved regions of Wnt-related proteins were used with the polymerase chain reaction (PCR) to amplify cDNA derived from Xenopus laevis embryos. cDNA sequences partially encoding seven additional members of the Xwnt gene family were isolated using this strategy. These cDNAs have been given the designation Xwnt-2, Xwnt-6, Xwnt-7A, Xwnt-7B, Xwnt-7C, Xwnt-8B and Xwnt-10 based on their amino acid identity with previously described Wnts. With regard to the timing of expression of these Xwnts during embryonic development, Xwnt-2, the least abundant transcript, was first detected during the neurula stage, while Xwnt-8B transcripts were first detected at the gastrula stage, and decreased by the tailbud stage. Multiple transcripts of Xwnt-6 were detected at varied times during development beginning at the gastrula stage. In contrast, Xwnt-7A, -7B and -10 transcripts were not detected until the tailbud stage. With regard to expression in adult tissues, Xwnt-6, -7A, -7B, -8B and -10 were all expressed abundantly in the brain, and to a lesser extent in a variety of other tissues. Whole-mount in situ hybridization was then employed to monitor the spatial expression of selected Xwnts. Xwnt-7A and -10 transcripts were detected in distinct areas of the developing brain of tailbud-stage embryos. The temporal and spatial differences in expression suggest different roles for these new Xwnt family members in Xenopus development.


Functional analysis of the SH2 and SH3 domains of the lck tyrosine protein kinase.

p56lck is a lymphoid cell-specific member of the src family of cytoplasmic tyrosine kinases. In helper and cytotoxic T cells it is physically associated with the CD4 and CD8 surface antigens and appears to play a role in signal transduction during T-cell activation. p56lck contains both an SH3 and an SH2 Src homology domain. Such domains have been suggested to play a role in the regulation of the activity or function of both receptor and non-receptor tyrosine protein kinases. Deletion of either or both domains in p56lck was found here to activate the protein and to lead to increased phosphorylation of the autophosphorylation site, Tyr-394, in vivo. These findings are consistent with the hypothesis that these domains participate in repression of the kinase activity of p56lck. None of the deleted forms was capable of transformation of fibroblasts. Deletion of the SH3 domain of a constitutively activated form of p56lck, p56lckF505, did not diminish the transforming activity of this protein. This suggests that this domain is dispensable for the transformation of fibroblasts by p56lck. In contrast, deletion of the SH2 domain abolished the transforming potential of activated p56lckF505. However, interpretation of this effect is made somewhat difficult because the mutation also lowered the steady-state abundance of the protein.


Promoter region of the murine fibroblast growth factor receptor 2 (bek/KGFR) gene.

Fibroblast growth factors (FGFs) and their receptors play an important role in cell growth, angiogenesis and embryonal development. Four distinct genes encoding fibroblast growth factor receptors (FGFRs) were identified: flg, encoding FGFR1, bek encoding FGFR2, and the genes for FGFR3 and FGFR4. Both FGFR2 and keratinocyte growth factor receptor (KGFR) are encoded by the same gene, bek. To study the regulation of expression of the FGF receptors we analysed the DNA sequence flanking the 5' region of the cDNA of murine FGFR2 to seek elements that control its transcription. A 5-kbp fragment containing the 5' end of the cDNA was isolated from mouse genomic library and used to map the promoter region. We found that the sequence encoding the 5' non-translated region of the FGFR2/KGFR cDNA contains an intron located 210 bp upstream from the translation start site. Using RNAase protection and primer extension, we identified the mRNA start 37 bp upstream from the beginning of the bek cDNA. The promoter activity was found to reside in a 1.3-kbp fragment upstream from the cDNA, and deletion mapping further localized the promoter to a 0.7-kbp fragment. The sequence of this region shows high G+C content (62%), which is particularly emphasized in the 200 bp upstream from the mRNA start (80% G+C). This region contains the CCGCCC, GGGCGG AND GGAGG motifs also found in promoters of other growth factor receptors. Neither TATA nor CAAT boxes were found near the RNA start site. The characterization of this promoter will allow studies of the regulation of expression of the FGFR2 during development and in pathophysiological states. The differences between the promoter sequence of the gene for FGFR2 (bek) and FGFR1 (flg) may explain their differential expression during development.


Mast cells sensitive to v-H-ras transformation are hyperinducible for interleukin 3 expression and have lost tumor-suppressor activity.

Subcloning of interleukin 3 (IL-3)-dependent PB-3c mastocyte cells revealed two populations, of which only one is sensitive to oncogenic transformation by v-H-ras. The corresponding tumors produce IL-3 and grow in vitro in the absence of exogenous IL-3 [Nair, A.P.K., Diamantis, I.D., Conscience, J.F., Kindler, V., Hofer, P. & Moroni, Ch. (1989). Mol. Cell. Biol., 9, 1183-1190]. In the present investigation, IL-3 gene regulation was compared in ras transformable (rT) and ras nontransformable (rNT) lines. We report that upon expression of v-H-ras rT clones but not rNT clones express low levels of IL-3 mRNA as detected by reverse polymerase chain reaction. Treatment with ionomycin, a calcium ionophore, induced high levels of IL-3 expression only in ras-expressing rT clones. Somatic cell fusion between the rNT clone 20 and the IL-3-expressing mastocytoma line V2D1 led to down-regulation of IL-3 expression and to the requirement for exogenous IL-3 for in vitro growth and tumor suppression. In contrast, rT clone 15 lacked tumor-suppressor activity and failed to down-regulate IL-3 expression in somatic hybrids which grew in vitro without added IL-3. Our results indicate that IL-3 gene expression is a critical determinant for the generation of v-H-ras-induced mast cell tumors and show that disturbances in IL-3 gene regulation can be detected already at the premalignant level in v-H-ras transformation-sensitive cells.


p53 and chromosome 3 abnormalities, characteristic of malignant lung tumours, are detectable in preinvasive lesions of the bronchus.

Bronchial epithelial dysplasia is believed to precede invasive squamous cell carcinoma of the lung. Six paired dysplasia and tumour samples were distinguished histologically in sections of formalin-fixed paraffin-embedded lung tissue from patients with lung cancer. Additionally, samples of dysplastic bronchial epithelium were obtained from patients without lung tumours. Microdissection of the unstained sections provided dysplastic and tumour samples from which DNA was prepared for comparison with the patients' constitutional genotype, using polymerase chain reaction-based restriction fragment length polymorphism analysis. All six samples of tumour and the paired adjacent samples of bronchial dysplasia showed loss of heterozygosity (LOH) at loci on the short arm of chromosome 3. Five of the six cases showed involvement of the p53 gene as assessed by LOH at the AccII site within the gene, and by immunoreactivity to CM-1, an antibody which recognizes the mutated form of the p53 protein in paraffin-embedded material. Of the dysplastic samples, obtained from patients without invasive tumours, all three showed LOH at 3p; one sample showed LOH at the AccII polymorphic locus within the p53 gene, and another sample, uninformative at this locus, stained positively with this antibody. These results indicate that somatic genetic changes are present in preinvasive lesions in the bronchus.


The c-myb proto-oncogene product binds to but does not activate the promoter of the DNA polymerase alpha gene.

The myb proto oncogene product (c-Myb) is a transcriptional regulator and its expression and function are tightly linked to the cellular entry into S phase and DNA synthesis. It has been shown [Venturelli, D., Travali, S. & Calabretta, B. (1990). Proc. Natl. Acad. Sci. USA, 87, 5963-5967] that inhibition of T-cell proliferation by a myb antisense oligomer is accompanied by down-regulation of DNA polymerase alpha expression. To examine whether the transcription of the DNA polymerase alpha gene is directly regulated by c-Myb, we have identified and characterized the 5' regulatory region of the human DNA polymerase alpha gene. Two major and several minor transcription start sites were identified by nuclease S1 mapping. DNA sequence analysis showed that the promoter region contains no TATA box, one CCAAT box and putative Ap-1, AP-2 and E2F binding sites. In DNAase I footprinting, the bacterially expressed c-Myb protected six sites in the 5' flanking region of the human DNA polymerase alpha gene. However, c-Myb did not activate the DNA polymerase alpha gene promoter in a co-transfection assay. Our results suggest that an unknown factor(s) is required for the c-Myb-induced activation of the DNA polymerase alpha gene promoter, or c-Myb does not directly activate this promoter.


First non-vertebrate member of the myc gene family is seasonally expressed in an invertebrate testis.

We have cloned and characterized the first non-vertebrate member of the myc gene family, pAv-myc, from testes of the Northern sea star, Asterias vulgaris (Echinodermata). We have used an oligonucleotide that is complementary to the virtually 100% conserved vertebrate c-myc box A in the second exon and a cDNA library constructed from spermatogenically active testes. Relatives of this echinoderm existed approximately 100 million years prior to the origin of the earliest known organism for which c-myc sequence is currently available (the trout). Nonetheless, our cDNA encodes a protein with approximately 30% amino acid identity and 46% overall conservation to human c-myc. Regions of substantially higher conservation (63-95%) correspond in order to the transcriptional activation (boxes A, B and C), casein kinase II phosphorylation, nuclear-targeting, basic DNA-binding and oligomerization domains in the second and third exons of human c-myc. Sea star c-myc cDNA detects a 2.7-kb transcript on Northern blots of monthly samples of testicular tissue from field-collected individuals (n = 6-8), indicating peak expression during active spermatogenesis. This is also the first example of seasonal variation in expression of c-myc during spermatogenesis in laboratory or natural populations of any animal. It is intriguing to speculate about the potential oncogenic character of c-myc in this invertebrate, in which tumors have not yet been observed, and about the possibility that c-myc is more widely present in eucaryotes than has been anticipated.


Suppression of tumorigenesis by the breast cancer cell line MCF-7 following transfer of a normal human chromosome 11.

Breast cancer development is associated with several genetic abnormalities. Loss of heterozygosity in the short arm of chromosome 11 has been observed in 30% of tumors. We found homozygosity at five chromosome 11 polymorphic loci in genomic DNA of the MCF-7 breast carcinoma cell line, suggesting a possible loss of one chromosome 11. We have studied the transformed and tumorigenic phenotypes of MCF-7 cells following introduction of a normal human chromosome 11 via microcell fusion. MCF-7/H11 cell hybrids, containing chromosome 11, showed in vitro characteristics similar to the parental cell line. However, tumorigenicity in athymic mice was completely suppressed. Since tumor formation by MCF-7 cells is estrogen dependent, we have analysed the expression of the estrogen receptor and of the estrogen-activated gene pS2. No difference was detected between the parental MCF-7 cells and the derived chromosome 11 cell hybrids, indicating that the mechanism of MCF-7 tumor suppression by chromosome 11-associated functions does not directly involve the estrogen/estrogen receptor molecular pathway.


Characterization of an angiosarcoma-inducing mutation in the erbB oncogene.

The erbB oncogenes of two transducing viruses that arose in chicken 5005 have been molecularly characterized. One of these viruses, AEV-5005, caused erythroblastosis. The other, AAV-5005, caused angiosarcoma. Both viruses had identical 5' junctions of viral and host sequences, indicating that both arose from the same proviral insertion. The erbB oncogenes of both viruses encoded transmembrane, kinase and C-terminal domains of the chicken epidermal growth factor receptor. The C-terminal domain of the AEV-5005 erbB was complete, whereas that of AAV-5005 contained a 59 amino acid internal deletion (amino acids 993-1051 of the chicken epidermal growth factor receptor). Oncogenicity tests using retroviral constructs containing the erbB sequences from AEV-5005 and AAV-5005 demonstrated that both erbB genes caused erythroblastosis and that the 59 amino acid deletion conferred the ability to induce angiosarcoma. The 59 amino acid deletion also caused increased levels of erbB autophosphorylation in cells grown in the presence of sodium orthovanadate.


Cooperation between the H-ras oncogene and a truncated derivative of the v-myb oncogene in transformation of hamster embryo fibroblasts.

The ras oncogenes alone fully transform established (immortalized) rodent fibroblasts in a few days, but generally transform early-passage fibroblasts only partially, unless their action is complemented by that of a nuclear, immortalizing, oncogene. Here we show that transfection of second-passage Syrian hamster embryo fibroblasts (HEFs) by the EJ-H-ras oncogene coupled to the neo gene, followed by selection with G418, gives rise to apparently normal, or only slightly transformed, clonal colonies, only a few of which become established. The study of two established clonal lines showed that they acquired only after some weeks, and stepwise, the main characteristics of full neoplastic transformation, i.e. anchorage independence, reduced requirement for serum growth factors and tumorigenicity. Later both clonal lines became increasingly tumorigenic and completely independent of exogenous growth and attachment factors, without increase in the expression of the H-ras oncogene. Transfection of one of the clones, early after its isolation, with a truncated derivative of the nuclear v-myb oncogene devoid of its transcriptional negative regulatory domain and able to partially transform chicken embryo fibroblasts [(myb(KXANM)] gave rise to more transformed cells, expressing both EJ-H-ras and myb(KXANM), which became tumorigenic earlier than the controls and remained more tumorigenic later on. With more efficient transfection techniques, numerous foci of fully transformed cells were subsequently obtained, in a few days, in cultures transfected sequentially with EJ-H-ras(neo) and myb(KXANM) and in cultures co-transfected with the two oncogenes. Highly tumorigenic, serum-independent and immortalized clones expressing both oncogenes were obtained from these cultures. Hence, the truncated myb(KXANM) oncogene accelerate the stepwise transformation of unestablished HEFs by the EJ-HH-ras oncogene and, together with this oncogene, fully transforms these same cells in a single step. The two oncogenes acting in cooperation also induce cell immortalization, but myb(KXANM), by itself, is not an immortalizing oncogene. No cooperation was observed between EJ-H-ras(neo) and the unaltered v-myb oncogene.


Hyperplasia of mouse mammary epithelium induced by expression of the Wnt-1 (int-1) oncogene in reconstituted mammary gland.

We have expressed the Wnt-1 (formerly int-1) oncogene in Balb/c mouse mammary epithelium in vivo, using a tissue reconstitution method in which primary cultures of mammary epithelial cells are infected with a retrovirus vector and then transplanted into mouse mammary fat pads from which the natural epithelium has been removed. Transplants carrying the Wnt-1 gene grew in a hyperplastic pattern, the duct epithelium showing abundant fine side-branches, but without development of clusters of alveoli. The hyperplasias were similar, but not identical, to transplants of normal epithelium in a mid-pregnant host. Transplants of epithelium that expressed Wnt-1 into mammary fat pads of male or ovariectomized females grew to form a similar three-dimensional pattern, but the extent of growth, and so presumably the rate of growth, was slower than in intact females, and there were no terminal end buds at the edges of the outgrowths. Thus, although Wnt-1 may enhance growth of epithelium in the male or ovariectomized-female environment, it does not restore the major mode of growth in the intact female, the extension of major ducts from terminal end buds. Normal epithelium showed no change in morphology when in close proximity to hyperplasia induced by Wnt-1, confirming the limited range of diffusion of Wnt-1 protein in vivo. Our results are consistent with the hypothesis that Wnt-1 acts principally by mimicking the signal that causes ducts to develop side-branches in pregnancy.


Altered H1 histamine receptor signaling in Balb/3T3 cells transformed by v-K-ras and v-H-ras oncogenes.

Transformation of Balb/3T3 cells with the v-K-ras oncogene resulted in the expression of functional Ca(2+)-mobilizing receptors for histamine, whereas v-H-ras-transformed Balb/3T3 cells failed to show a similar response to histamine. Stimulation of histamine receptors in v-K-ras-transformed cells produced a dose-dependent increase in intracellular free calcium ([Ca2+]i), which was inhibited by the H1 histamine antagonist pyrilamine but unaffected by the H2 histamine receptor antagonist cimetidine. Histamine-mediated elevation of [Ca2+]i was partially inhibited by the removal of extracellular Ca2+, which indicates that the H1 histamine receptors mobilize intracellular Ca2+ and also promote Ca2+ influx. H1 histamine receptors were identified in both v-K-ras- and v-H-ras-transformed Balb/3T3 cells, but not in untransformed cells, using the specific H1 antagonist [3H]-pyrilamine. Transformation of Balb/3T3 cells with the viral ras oncogene results in a complex regulation of H1 histamine receptors. K-ras and H-ras transformation results in the expression of H1 histamine receptors; however, H1 receptor expression and Ca2+ mobilization are uncoupled in v-H-ras-transformed cells.


Sequence and expression of a murine cDNA encoding PC326, a novel gene expressed in plasmacytomas but not normal plasma cells.

Using a subtractive cDNA approach we have identified a gene, PC326, expressed in 13 of 14 murine plasmacytoma cell lines, but not in any B- or pre-B-lymphoma cell lines. It expresses 4.6-kb and 5.2-kb mRNAs that encode a 747 amino acid protein containing two highly acidic domains flanking a novel, moderately acidic 20 amino acid sequence that is repeated 7.5 times. Sequence comparison identifies an additional 43 amino acid domain that is homologous to a repeated sequence found in the members of the beta-transducin gene family. The PC326 mRNA is detectable in testis but in no other murine tissues, including plasma cells induced by lipopolysaccharide stimulation of splenocytes. Somatic cell hybrids derived from plasmacytomas and fibroblast or T-cell lines have a fibroblastic or T-cell phenotype respectively. Unlike B-cell-specific genes (e.g. immunoglobulin), the expression of which is extinguished in these hybrids, PC326 mRNA appears to be irreversibly turned on in these hybrids. Since PC326 is not expressed in normal plasma cells, it appears that its expression is a cause or consequence of the tumorigenic process that generates murine plasmacytomas.


Evidence that activation of the Egr-1 promoter by v-Raf involves serum response elements.

The constitutively active serine/threonine kinase encoded by the v-raf oncogene, v-Raf, activates the Egr-1 promoter in transient expression assays. To characterize the v-Raf-responsive transcriptional control elements, deletion mutants of the Egr-1 promoter were used in transient expression assays. A v-Raf expression vector was co-transfected into NIH3T3 cells with reporter chloramphenicol acetyl transferase (CAT) expression vectors under the control of the Egr-1 promoter or the Egr-1 promoter containing various deletions. Responsiveness to v-Raf was restricted to a region that contained repeated CC(A/T)6GG sequences, known as CArG boxes. CArG boxes form the core of serum response elements (SREs). v-Raf-induced Egr-1 promoter activation was lost by removal of the four tandemly repeated SREs. This region, between -425 and -250, which was necessary for v-Raf responsiveness, was also found to be sufficient for maximal Egr-1 induction by v-Raf when placed upstream from a minimal heterologous promoter. Three out of four SREs from this region were able to respond to v-Raf, however the activation of the individual SREs was lower than the clustered SREs. This cluster of SREs has previously been shown to be responsive to several mitogenic stimuli and the oncogene v-src. Thus, the SREs contained in this cluster may be an important target for cell division signals.


Early loss of heterozygosity on 17q in ovarian cancer. The Abe Ovarian Cancer Genetics Group.

We have studied 146 ovarian tumours (94 carcinomas, 22 tumours of low malignant potential and 30 benign tumours) for evidence of allele loss on chromosome 17p and 17q sufficient to imply the proximity of a tumour-suppressor gene. We have examined two polymorphic loci (YNZ22.2 and BHP53) on 17p13 and one on chromosome 17q (17q23-qter). Loss of heterozygosity (LOH) was detected in 34/63 (54%) informative malignant tumours at YNZ22.2 and 22/47 (47%) at BHP53; on 17q, 45/64 (70%) had LOH. Allele loss was detected in a small number of benign and borderline tumours. There was a statistically significant difference between the patterns of allele loss in serous and endometrioid groups of tumours, and allele loss occurred with significantly greater frequency on 17q than on 17p. Comparison of all malignant tumours presenting with either localized (FIGO stage I/II) or widespread (FIGO stage III/IV) disease showed that, particularly on 17q, allele loss increases in the more advanced stages. The p53 tumour-suppressor gene is implicated in ovarian carcinogenesis, and our findings suggest that an important tumour-suppressor gene may be located in the region 17q23-qter. Loss of function in this gene may be responsible for the frequently observed rapid progression of serous-type adenocarcinomas to an advanced stage.


c-Jun causes focus formation and anchorage-independent growth in culture but is non-tumorigenic.

The RCAS retroviral vector was used to express chicken and mouse cellular Jun proteins in chicken embryo fibroblasts. Both mouse and chicken proteins induced foci of transformed cells with low to moderate efficiency compared with viral Jun, but were as effective as the viral protein in promoting anchorage-independent growth. Viral Jun and a recombinant between viral and cellular Jun induced tumors in 1-day-old chicks; the cellular Jun proteins were uniformly non-tumorigenic.


A retroviral sequence of the Chinese hamster ovary cell line.

A partial cDNA (B52) molecule with the characteristics of retroviral sequences was isolated from the Chinese hamster ovary (CHO) K1 cell line. The B52 cDNA contains 1184 nucleotides. The first 452 nucleotides (nt) are 71% homologous to the env gene of Moloney murine leukemia virus (MMLV) and murine endogenous retroviruses. The 139 amino acids predicted from the 452 nt have 82% homology with the carboxy-terminal amino acids of the env protein of MMLV. The remaining 732 nt have several features of a typical retroviral long terminal repeat (LTR). For example, the first 14 nt are identical to the 5' inverted repeat of the retroviral LTRs. The 41-nt sequence at the 3' end is common to the R region of retroviral LTRs. The 732-nt sequence was shown to have promoter activity. The activity is approximately twofold higher than that of the Rous sarcoma virus LTR, and 1.5-fold lower than that of the early promoter of SV40 virus. Two species of mRNA of 5.2 and 2.7 kb in size were readily detected by B52 cDNA in the CHO K1 cells.


Mutational analysis of Max: role of basic, helix-loop-helix/leucine zipper domains in DNA binding, dimerization and regulation of Myc-mediated transcriptional activation.

The Max protein forms a heterodimeric complex with the Myc family of proteins and binds to DNA in a sequence-specific manner. We investigated the role of the helix-loop-helix (HLH), leucine zipper (LZ) and basic domains of Max in protein complex formation, DNA-binding activity and transcriptional regulation. We mutagenized the basic, HLH and LZ domains of Max and studied the ability of the normal and mutant proteins to bind to DNA as both homo- and heterodimers and their ability to heterodimerize with Myc. Helix-1 and helix-2 regions of Max were found to be critical for homodimer formation and subsequent DNA binding, while the LZ was essential for heterodimer formation. In transient transfection assays the Myc protein functioned as a transcriptional activator while Max protein repressed the trans-activation observed with Myc.


Motion reveals spatial visual defects.

The question of how we can be unaware of the deficit in our (monocular) visual field, equivalent in size to 76 full moons, is examined. A new method of investigating the response to moving images on and near the blind spot has been found. The image of a computer-generated line, which is made to lengthen with time and pass over the blind spot, is seen as shorter than that of a similar, parallel line which passes outside the blind spot. This perceived difference in length corresponds to the actual width of the blind spot. Our unawareness of blind spots and scotomata is often described as involving some form of 'filling in' process. The rapid variation in cortical receptive field size, recently found to occur in response to stabilized images, may provide a general filling-in mechanism for the removal from perception of otherwise-distracting, stabilizing image regions (such as the shadows of blood vessels and clinical scotomata).


New method based on random luminance masking for measuring isochromatic zones using high resolution colour displays.

A new method of measuring normal hue discrimination ellipses and dichromatic zones using a high resolution colour monitor is described. The test involves the detection of chromatic bars on a grey background (x = 0.305, y = 0.323) having a luminance of 34 cd m-2. Elements of the background matrix of square checks are varied randomly in luminance in space and time to provide random luminance masking (RLM) which compensates for differences in the relative luminous efficiency of different observers. The measurement technique provides a rapid and comprehensive colour vision test. Typical results are presented for normal trichromats, protanopes and deuteranopes without RLM and with the RLM set of 25%. The size of the discrimination ellipse in normal observers is the same in both viewing conditions, but the use of the RLM technique reveals the extent of the isochromatic zones in colour deficient observers.


Pupillary responses to stimulus structure, colour and movement.

Pupillary responses to stimuli which favour the preferential stimulation of neural mechanisms involved in the detection of visual attributes such as colour, spatial structure, movement and light flux changes on the retina have been measured and compared. Pupil responses to a decrement in stimulus luminance (i.e., a flash of darkness), suggest that at least three components are involved in this response, their relative contribution being determined largely by stimulus size, contrast and presentation time. A comparison of pupil responses to gratings of equal and lower space-averaged luminance shows that the amplitude of pupillary constriction at grating onset for the equal luminance condition is about twice that measured with similar gratings in the lower luminance condition. Pupillary responses to chromatic isoluminant gratings are in general of longer latency when compared to responses of similar amplitude elicited by achromatic gratings. Small pupillary constrictions elicited by the onset of coherent movement in dynamic, random dot patterns are also demonstrated under stimulus conditions which eliminate pupillary responses to sudden light flux changes on the retina. The results support an earlier hypothesis which suggests that the onset of sudden changes in neural activity in the visual cortex when a visual stimulus is presented to the eye causes an overall perturbation which weakens transiently the regulatory inhibitory input to the pupillomotor nucleus. This, in turn, results in a transient increase in the efferent parasympathetic innervation of the iris sphincter muscle and hence the observed constriction of the pupil. The characteristics of the pupillary response reflect the properties of the mechanisms and the number of neurones which participate in the detection of each stimulus attribute.


Non-linear processes in perceived region segregation: orientation selectivity of complex channels.

Models incorporating linear spatial-frequency- and orientation-selective channels explain many aspects of visual texture segregation. The inability of such models to fully explain texture segregation results, indicates that non-linear processes are also involved. One non-linearity that has been suggested is complex channels consisting of two stages of linear filtering separated by a rectification-type non-linearity (much like cortical complex cells). Here we further demonstrate the usefulness of complex channels in explaining texture segregation results and investigate the orientation-selectivity of the first stage of such complex channels. Our results suggest that the first stage is much more selective for orientation than are lateral geniculate nucleus cells, but that the first-stage orientation bandwidth is rather wide with some interaction occurring between perpendicular orientations.


Geometrical optical analysis of photorefractive methods.

Photorefractive methods allow rapid measures of the refractive and accommodative state of infants and young children whose brief attention and co-operation limit the use of more traditional methods such as retinoscopy and autorefraction. Three methods have been defined: orthogonal, isotropic and eccentric. We provide a common geometrical optical analysis for these three methods where the photorefractive pattern is defined at the plane of focus of the camera. Since this plane is conjugate with the detector plane of the camera then the critical optical parameters can be defined without reference to the design of the camera by simply determining the relative magnification of the projected image of an object photographed at the camera's plane of focus. Specifically the pattern width CF (mm) over a photorefractor's working range can be defined for the isotropic and orthogonal methods as: [formula: see text] and for the eccentric method as: [formula: see text] where: K is a myopic refractive error of the eye (dioptres) (K Less than 0); P the distance of the flash source to the eye (dioptres); L the distance in front of the eye of the camera's plane of focus (dioptres) (L less than 0); GH the pupil diameter (mm); e the eccentricity of the flash source from the camera aperture (mm); M magnification of the image measured relative to the camera plane of focus.


Counterphase dichoptic flicker is seen as its own second harmonic.

If a patternless field is modulated sinusoidally in time so that the luminance change in one eye is in counterphase to that in the other, the resulting flicker appears faster than if the modulation to both eyes has the same phase. If observers set the frequency and the amplitude of a comparison in-phase field so that it matches a neighbouring counterphase field, modulated at, say, 2.5 x its threshold, they set the frequency to twice the counterphase frequency, and the amplitude to a value that is, for a given frequency, a constant ratio of the modulation of the counterphase field. Counterphase stimulation thus appears to cause an internal second-harmonic signal. However, it is not possible to cancel this by adding a second harmonic component to the stimulus.


Immediate colour constancy.

Colour constancy is traditionally interpreted as the stable appearance of the colour of a surface despite changes in the spectral composition of the illumination. When colour constancy has been assessed quantitatively, however, by observers making matches between surfaces illuminated by different sources, its completeness has been found to be poor. An alternative operational approach to colour constancy may be taken which concentrates instead on detecting the underlying chromatic relationship between the parts of a surface under changes in the illuminant. Experimentally the observer's task was to determine whether a change in the appearance of a surface was due to a change in its reflecting properties or to a change in the incident light. Observers viewed computer simulations of a row of three Mondrian patterns of Munsell chips. The centre pattern was a reference pattern illuminated by a simulated, spatially uniform daylight; one of the outer patterns was identical but illuminated by a different daylight; and the other outer pattern was equivalent but not obtainable from the centre pattern by such a change in illuminant. Different patterns and different shifts in daylight were generated in each experimental trial. The task of the observer was to identify which of the outer patterns was the result of an illuminant change. Observers made reliable discriminations of the patterns with displays of durations from several seconds to less than 200 ms, and, for one observer, with displays of 1 ms. By these measures, human observers appear capable of colour constancy that is extremely rapid, and probably preattentive in origin.


Retinal information capacity and the function of the pupil.

When the pupil is opened to increase sensitivity there is a loss of image sharpness due to aberrations. This trade-off between sensitivity and sharpness is analysed theoretically by calculating the information capacity of the retinal image. The analysis uses optical measurements of image sharpness made at different pupil diameters. At each luminance there is a pupil diameter that maximizes information capacity. This optimum is close to the diameter adopted under normal viewing conditions. The optimum is broad, consequently the system tolerates inaccurate adjustment. The benefits of correctly adjusting the pupil are evaluated. At low light levels the advantage is 68%, at intermediate levels it falls to around 20% but under daylight conditions it increases to 52%. These advantages suggest that the primary function of the pupillary light reflex is to maximize acuity over a wide range of luminances.