Are you using a different kind of filmholder than you've used in the past? It sounds like the filmholder isn't going in all the way if you're having a sharpness problem of the sort you describe, and then the obstruction would be connected to that.
I think on some Cambo 4x5" cameras there is a metal bracket on the back that is used to hold a cable release that connects to an automatic shutter system and stops down the diaphragm when the filmholder is inserted, and this bracket does not work with certain types of filmholders, like Grafmatics, and perhaps the Readyload or Quickload holders. Some people who don't own the automatic shutter system and never intend to own it just grind off the bracket.
I'm a little unsure from your description, but another problem could be a bellows obstruction, but if you're getting this in both the vertical and horizontal orientations it wouldn't be that, and it wouldn't explain the sharpness problem in any case.