Identification of primary lysosomes in human megakaryocytes and platelets

The presence of lysosomal enzymes in human platelets is well documented; the identity of the "lysosome," however, has been the subject of some disagreement. In order to determine the time of appearance and subcellular localization of two lysosomal enzymes in megakaryocytes (MK) and platelets, we examined normal human bone marrow and blood by electron microscopy and cytochemistry. Acid phosphatase (AcPase) was present in the Golgi region in the youngest recognizable MK, as well as in those with a considerable degree of cytoplasmic maturation. Heavy reaction product was usually confined to one or two Golgi-associated cisternae and coated vesicles; other Golgi cisternae were sometimes lightly reactive. In mature MK, reaction product was limited to vesicles of variable size, but smaller than alpha-granules. Another lysosomal enzyme, arylsulfatase (AS), was localized in similar small vesicles in MK of all stages; it could not be demonstrated in the Golgi complex. Vesicles containing AS were also found in about 25% of platelet profiles, whereas vesicles containing AcPase were found in only about 15% of platelet profiles. The alpha-granules of all MK and platelets examined were negative for both enzymes. We conclude that the enzyme-containing vesicles in these cells constitute the lysosomes and that they are distinct from other platelet organelles. Since there was no evidence that they had participated in any digestive event, we believe that they are primary lysosomes, whose contents are secreted during platelet aggregation and the release reaction.     

A clinical study comparing methyl aminolevulinate photodynamic therapy and surgery in small superficial basal cell carcinoma (8–20 mm), with a 12‐month follow‐up.

Objective To compare the efficacy and cosmetic outcome (CO) of photodynamic therapy with topical methyl aminolevulinate (MAL‐PDT) with simple excision surgery for superficial basal cell carcinoma (sBCC) over a 1‐year period. Methods In this multicentre, randomised, controlled, open study, patients were treated at baseline either with MAL‐PDT (two sessions, 7 days apart, repeated 3 months later if incomplete clinical response) or surgery (at baseline). Primary endpoints were clinical lesion response (CR) 3 months after last treatment and CO assessed by the investigator 12 months after last treatment. Secondary endpoints were CR at 12 months (i.e. recurrence) and CO assessed by the investigator at 3 and 6 months and by the patient at 3, 6 and 12 months. Results Overall, 196 patients were enrolled with 1.4 sBCC lesions on average per patient. Mean lesion count reduction at 3 months was 92.2% with MAL‐PDT vs. 99.2% with surgery [per protocol (PP) population] confirming the non‐inferiority hypothesis (95% confidence interval, –12.1, –1.9). A total of 92.2% lesions showed CR at 3 months with MAL‐PDT vs. 99.2% with surgery (PP population). At 12 months, 9.3% lesions recurred with MAL‐PDT and none with surgery. CO was statistically superior for MAL‐PDT at all time points. At 12 months, 94.1% lesions treated with MAL‐PDT had an excellent or good CO according to the investigator compared with 59.8% with surgery. This difference was confirmed with the patients’ assessment. The proportion of excellent CO markedly improved with time with MAL‐PDT unlike surgery. Conclusions MAL‐PDT offers a similarly high efficacy and a much better CO than simple excision surgery in the treatment of sBCC.