Intramuscular haemangiomas: hookwire localization prior to surgical excision: report of four cases.

BACKGROUND: Haemangiomas of skeletal muscle are a rare entity, although they are still noted to be one of the most common deep tissue tumours of the lower limb. All such lesions are benign with no recorded evidence of metastasis; but they are associated with a 17-20% local recurrence rate which is thought to be related to inadequate primary surgical excision rather than histological subtype. METHODS: The present case series briefly discusses the pathophysiology, clinical manifestations, diagnostics, differential diagnosis and treatment modalities of intramuscular haemangiomas. The article then focuses on the recent introduction of ultrasound-guided hook-wire localization, which has enabled a great increase in complete surgical excision, resulting in much lower rates of local recurrence and a more pleasing functional and cosmetic result because unnecessary dissection is avoided. RESULTS: Preoperative ultrasound-guided hookwire localization of deep and often non-palpable intramuscular haemangiomas was very helpful in enabling a more complete surgical excision to be carried out. CONCLUSION: Hookwire localization using ultrasound guidance is an invaluable tool in directing the surgeon intraoperatively when excising deep intramuscular haemangiomas.

Advanced gastroduodenal polyposis with ras mutations in a patient with familial adenomatous polyposis.

Upper gastrointestinal polyps are being recognized with increasing frequency in patients with familial adenomatous polyposis. Duodenal and periampullary adenomas are the most common type and have poorly understood but definite malignant potential. In contrast, the majority of polypoid lesions in the stomach are benign fundic gland polyps. We report a patient with familial adenomatous polyposis who developed dysplasia in a large exophytic hyperplastic gastric tumor that appeared to arise on a background of diffuse fundic gland polyposis and presented with anemia, hypoalbuminemia, and a protein-losing enteropathy. A large periampullary adenoma also was present. Using the polymerase chain reaction with mismatched primers, a GGT to TGT Kras codon 12 mutation was detected within areas of severe dysplasia in the gastric tumor and in the periampullary adenoma. This case serves to further highlight the spectrum of clinical, pathologic, and molecular features of premalignant upper gastrointestinal tract lesions in patients with familial adenomatous polyposis.

Potassium depletion inhibits the intracellular transport of secretory proteins between the endoplasmic reticulum and the Golgi complex.

In this paper we show that hepatocytes that have been depleted of K+ secrete albumin, alpha-1-anti-trypsin and transferrin at a slower rate than cells to which K+ has been returned. K+ depletion has no effect on the intracellular nucleotide pools, and we provide evidence that the inhibitions of secretion caused by depletion of K+ and depletion of ATP are independent. Studies of the processing of alpha-1-anti-trypsin show that K+ depletion inhibits the formation of the mature form of the protein, but that immature forms are never secreted. In cells to which K+ was returned, secretion of the mature form was restored. This implies that transport is blocked at a point before the proteins reach the processing enzymes. Proteins delayed by K+ depletion are not removed from the secretory pathway, but are free to mix with protein synthesized subsequently. These data are supported by subcellular fractionation experiments, which show that the secretory proteins are delayed before reaching the Golgi complex, and by immunoelectron microscopic studies. These show that in K+-deficient cells the morphology of both the endoplasmic reticulum and the Golgi complex is normal. The secretory proteins are trapped in smooth vesicles that contain reaction product when incubated for glucose-6-phosphatase, a marker for the endoplasmic reticulum.

Use of formylated yeast initiator Met tRNA to define the NH2-terminal residues of rat preproinsulin and pregrowth hormone.

A method for unambiguously determining the initiator methionine residue and the adjacent NH2-terminal amino acid sequence of cell-free translation products of eukaryotic messenger RNA is described. In this procedure, the NH2 termini of nascent peptides are blocked by incorporating labeled formylmethionine instead of methionine, using yeast initiator tRNA in the wheat germ cell-free system. After immunoprecipitation of the desired product the radiolabeled material is treated with dansyl-Cl to irreversibly block all remaining free amino groups. The material is then deformylated by mild acid hydrolysis and subjected to automated Edman degradation. Only those products that had been synthesized with formylmethionine residues at their NH2-termini can then give rise to labeled phenylthiohydantoin derivatives during degradation. Using this method, we have defined the initiation sites in both rat preproinsulin and pregrowth hormone messenger RNAs.

Formation of biologically active peptides.

Many small biologicaly active peptides are derived from larger precursor forms which fulfil a variety of roles in the synthesis, segregation and intracellular migration of secretory products. Limited proteolysis may occur at several stages during this process, giving rise to products that are either degraded (e.g. the prepeptides) or discharged coordinately from their cells of origin during exocytosis (e.g. insulin and C-peptide). Molecular defects have recently been found to occur at cleavage sites in proinsulin as well as in other proproteins, and these point mutations may, in some instances, be responsible for familial metabolic disorders. The nature and cell specificity of the proteolytic enzymes involved in the conversion of the various precursor forms remains unresolved. Recent studies in our laboratory have led to the identification of precursors of glucagon and somatostatin in rat islets of Langerhans. Analysis of tryptic maps of these precursors has shown that a trypsin-like enzyme would be sufficient to cleave the C-terminally located somatostatin sequence from its precursor (relative molecular mass 12,500), but that both trypsin-like and carboxypeptidase B-like enzymes would be necessary to cleave the internal glucagon sequence from its prohormone (relative molecular mass 18,000). Molecular cloning techniques have provided valuable new approaches to analysing the structures of a variety of precursor forms, including those for insulin, gastrin, growth hormone, adrenocorticotropic hormone and the endorphins, and in the future will undoubtedly shed more light on the structures of their chromosomal genes, the mechanisms regulating their expression, and their evolutionary origins.

Processing mechanisms in the biosynthesis of proteins.

Limited proteolysis is a widely occurring mechanism in protein biosynthesis. Protein precursors can be classified according to their functions, localization within cell compartments, and enzymic cleavage mechanisms. The presecretory proteins represent an important class of very rapidly turning over precursors which play an early role in the sequestration of secretory products and whose cleavage appears to be intimately associated with structures formed at the ribosome-membrane junction during protein synthesis. A model is proposed which predicts that the prepeptide forms a beta-pleated sheet structure with other components of the membrane which results in the transfer of a loop of peptide across the microsomal membrane. Proinsulin is representative of the general class of proproteins that are processed post-translationally within their secretory cells either during the formation and maturation of secretory granules (peptides hormones and neurotransmitters, serum albumins) or during the assembly of macromolecular structures (virus capsules, membrane-associated enzyme complexes). The former group are cleaved by Golgi-associated proteases having tryptic and carboxypeptidase B-like specificity. Some precursors are secreted as such and processed extracellularly either in the circulation or at special sites (procollagens, zymogens, provenoms, vitellogenins).

Calcium-dependent Golgi-vesicle fusion and cathepsin B in the conversion of proalbumin into albumin in rat liver.

1. An enzyme from rat liver that converts proalbumin into albumin is described. Partial purification, inhibitor studies and the conditions for maximum activity suggest that the enzyme is cathepsin B. 2. A membrane-bound enzyme, located mainly in lysosomes, also converts proalbumin into albumin. This appears to be a membrane-bound form of cathepsin B. 3. Isolated Golgi vesicles, incubated under conditions suitable for cathepsin B, convert endogenous proalbumin into albumin. 4. This conversion in Golgi vesicles has an absolute requirement for Ca2+ at micromolar concentrations. Mg2+ does not affect or substitute for Ca2+. Both the proalbumin and the albumin formed from it are intravesicular. 5. Converting activity is enhanced by pretreatment with the known chemical fusogen, poly(ethyleneglycol). 6. Vesicles preincubated at pH above 7 in the presence of dithiothreitol show a marked fall in converting activity. This can be partially restored by incubation with native vesicles. These results suggest that vesicle fusion is a requirement for conversion of proalbumin into albumin.

Evidence for the coupling of biosynthesis and secretion of serum albumin in the rat. The effect of colchicine on albumin production.

1. By using isotopic-dilution techniques it was found that colchicine causes a slight increase in the proalbumin content of liver, from 0.63+/-0.06 to 0.83+/-0.10mg/g of liver, but has no effect on albumin content (0.50+/-0.05mg/g of liver). All the proalbumin and 67% of the albumin is found in vesicles from which they are liberated by detergents. 2. Colchicine inhibits secretion of albumin, decreases the rate of conversion of proalbumin into albumin and decreases the rate of incorporation of l-[1-(14)C]leucine into proalbumin. 3. Balance studies in vivo show that all the (14)C appearing in serum albumin can be accounted for by the flow of (14)C through the proalbumin, in the presence or absence of colchicine. 4. When cycloheximide is given to the rats, 2min after [(14)C]leucine, further synthesis of protein stops. The label in proalbumin disappears and the proalbumin content of the liver falls, so as to account for the albumin appearing in the plasma. This occurs both in the presence and in the absence of colchicine. By contrast, there is little change in liver albumin. Studies with isolated perfused livers are in agreement with the above. Lumicolchicine has no effect on any of these systems at doses at which colchicine exerts its action. 5. These results suggest that biosynthesis and conversion of proalbumin into albumin, and secretion of serum albumin are controlled at each step.

Biosynthesis of serum albumin in rat liver. Isolation and probable structure of 'proalbumin' from rat liver.

1. Two methods are described for the preparation of 'proalbumin' in good yields from rat liver. 2. One of the methods does not depend on the use of specific antisera. 3. The product from both methods is identical as judged by electrophoresis on polyacrylamide gel, isoelectric focusing on pH gradients, ion-exchange chromatography and quantitative immunoelectrophoresis. The protein also appears to be radiochemically pure by these criteria. 4. The protein is free from serum albumin as judged by isoelectric focusing and co-chromatography on ion-exchange columns. It is judged to be free from other proteins by these same criteria and by specific precipitation with antibody. 5. It is converted into serum albumin by limited tryptic hydrolysis. The albumin so produced has the same N-terminal (glutamic acid) and C-terminal (alanine) amino acids as reported for rat serum albumin. 6. A hexapeptide is liberated from the N-terminal end of 'proalbumin' simultaneously. It contains three arginine, one phenylalanine, one valine and one glycine residues.