A viral protease-mediated cleavage of the transmembrane glycoprotein of Mason-Pfizer monkey virus can be suppressed by mutations within the matrix protein.

The envelope glycoprotein precursor of retroviruses undergoes proteolytic cleavage in the Golgi complex to yield the mature surface and transmembrane (TM) glycoproteins of the virus. We report here that the TM glycoprotein of Mason-Pfizer monkey virus undergoes a second proteolytic processing event during a late maturation step that can follow virus release and Gag polyprotein cleavage. Cleavage results in the conversion of the cell-associated TM glycoprotein (gp22) to a virus-associated gp20. Processing continues after virus release and yields virions that contain predominantly gp20. A mutation within the active site of the Mason-Pfizer monkey virus aspartyl protease was shown to block both TM glycoprotein cleavage and the processing of the Gag polyprotein precursor. The role of the viral protease in cleavage of the TM glycoprotein localizes the cleavage site to the cytoplasmic domain of this protein. Surprisingly, point mutations within the matrix (MA) coding region of the gag gene can affect the extent to which gp22 is processed to gp20 and in one case [p10(MA)-A79V] results in greater than 90% inhibition of gp22 cleavage. The data provide genetic evidence of a specific interaction between the capsid proteins and the cytoplasmic domain of the TM glycoprotein of a retrovirus. This interaction is required for cytoplasmic domain cleavage to occur and may play a critical role in virus assembly and viral infectivity.     

Oesophageal atresia: Diagnosis and prognosis in Dakar,Senegal

Background:

Oesophageal atresia is a neonatal emergency surgery whose prognosis has improved significantly in industrialised countries in recent decades. In sub-Saharan Africa, this malformation is still responsible for a high morbidity and mortality. The objective of this study was to analyse the diagnostic difficulties and its impact on the prognosis of this malformation in our work environment.

Patients and Methods:

We conducted a retrospective study over 4 years on 49 patients diagnosed with esophageal atresia in the 2 Paediatric Surgery Departments in Dakar.

Results:

The average age was 4 days (0-10 days), 50% of them had a severe pneumonopathy. The average time of surgical management was 27 h (6-96 h). In the series, we noted 10 preoperative deaths. The average age at surgery was 5.7 days with a range of 1-18 days. The surgery mortality rate is 28 patients (72%) including 4 late deaths.

Conclusion:

The causes of death were mainly sepsis, cardiac decompensation and anastomotic leaks.Key words: Esophageal atresia, Diagnosis, Prognosis, Sub-Saharan Africa     

Atrial flutter. Electrocardiographic,vectorcardiographic and echocardiographic correlation

The duration, contour, and amplitude of atrial flutter wave (f) was studied by electrocardiogram (ECG) and vectorcardiogram (VCG) in 32 patients and was related to the size of the left atrium (LA) measured by the echocardiogram (E). The following ECG parameters were analyzed: (1) the duration of left atrial depolarization, i.e., LA wave; (2) the amplitude of LA wave; (3) the surface area of LA wave; (4) maximum amplitude (A) of f in Leads 2 and V₁. There was good correlation between LA size and the duration of depolarization and surface area (p < 0.01), but the maximum amplitude of the f wave in Leads 2 and V₁ failed to predict LA size.The post-conversion sinus P wave showed abnormal LA depolarization time (P > 0.12 sec.) in 62 per cent of patients with enlarged left atrium (ELA) and in 43 per cent of patients with normal size LA (NLA).The VCG of the flutter wave revealed two patterns, (1) an eliptical smooth fsÊ loop in 63 per cent of patients with NLA, and (2) distorted fsÊ loop in 67 per cent of patients with ELA.Both VCG patterns were subdivided in two subgroups according to the number and location of conduction delays. The VCG of post-conversion P wave confirmed conduction delays in both groups.We conclude that both the size of the left atrium and conduction delays play a basic role in the duration and contour of left atrial wave.     

Long-term gonadal toxicity after therapy for Hodgkin's and non-Hodgkin's lymphoma

Summary With the increasing cure rate of patients treated for Hodgkin's and non-Hodgkin's lymphoma, the evaluation of late effects on gonadal function remains an important issue. The gonadal function of relapse-free long-term survivors with high-grade non-Hodgkin's lymphoma (NHL) and Hodgkin's disease (HD) were studied; 24 of 119 patients with NHL treated between 1980 and 1990 and 66 of 364 patients with HD treated between 1975 and 1990 at Hannover University Medical School, who were younger than 45 years of age and in complete remission at the time of evaluation for at least 24 months after completion of therapy, were included into the analysis. Of 24 patients with NHL, 1/10 women (10%) and only 3/14 men (21%) showed signs of gonadal dysfunction. Three of these four patients had been treated with combined modality therapy followed by maintenance COP chemotherapy, resulting in high cumulative doses of cyclophosphamide (range: 12–43 g). In comparison, 13/26 (50%) women with HD suffered from premature ovarian failure, and 26/40 (65%) men showed signs of gonadal dysfunction with significant FSH elevations. No significant difference in the incidence of gonadal toxicity existed in patients treated with combined modality who received irradiation to either supra- or infradiaphragmatic radiation fields in combination with chemotherapy (70% versus 62%). A comparison of the chemotherapy regimens used in patients with NHL or HD shows that patients from both groups had received comparable median cumulative doses of cyclophosphamide, vincristine, and adriamycin, but only patients with HD had additionally received a median cumulative dose of 13.3 g of procarbazine per patient. A tendency towards a higher incidence of gonadal toxicity with higher cumulative doses of procarbazine received was found in patients with HD. The frequency of gonadal dysfunctions is markedly lower in patients treated for non-Hodgkin's lymphoma than in patients treated for Hodgkin's disease, approximately half of whom will be affected by long-term gonadal toxicity. Although the use of more intensive radiotherapy in patients with HD compared with NHL patients makes the evaluation of the influence of radiotherapy on gonadal toxicity more difficult, the current retrospective analysis raises the concern that, in addition to infradiaphragmatic radiotherapy, the use of procarbazine in regimens for the treatment of HD, like COPP or MOPP, may be a possible explanation for the differences in gonadal toxicity observed between patients with HD and those with NHL. Regimens including procarbazine should be avoided in patients wanting to preserve fertility since alternative chemotherapies with at least equal efficacy are available.