The human pancreatic stone protein.

Chronic calcifying pancreatitis (CCP) is characterized by the presence of stones in pancreatic ducts. Calcium carbonate (CaCO3) is the main constituent of stones, to which is associated an organic matrix consisting primarily of one protein of Mr 14,000, the pancreatic stone protein or PSP. PSP is not present as such in pancreatic juice, but in polymorphic forms with higher molecular weights. These secretory forms (PSP S2-5, Mr 16-19,000) are synthesized in the acinar cells of the pancreas and secreted along the same secretory pathway as the exocrine enzymes. The heterogeneity of the forms of higher Mr (PSP S2-5) is probably due to different glycosylation patterns. PSP and PSP S1 are generated by the cleavage of an Arg-Ile bond in the N-terminal part of PSP S2-5. The N-terminal sequence of PSP (40 amino acids) is identical to that of PSP S1, whose complete sequence (133 amino acids) has been determined. Yet, the two proteins differ by their pI. Pancreatic juice is normally supersaturated in CaCO3, suggesting the presence of a stabilizer preventing CaCO3 precipitation. The PSP S could play that role, since an activity inhibiting the nucleation and growth in vitro of CaCO3 crystals was found in pancreatic juice, associated with these proteins. Moreover, PSP S concentration was significantly lower in the pancreatic juice of patients with CCP than in control patients. Proteins homologous to PSP S were also found in the dog, rat, swine, monkey and ox. They constitute a new family of pancreatic secretory proteins, whose biological role would be to maintain pancreatic juice in a stable state towards CaCO3.

Conjunctival concretions. Polarized microscopic, histopathologic, and ultrastructural studies.

To elucidate the pathophysiologic features of conjunctival concretions, we performed polarized microscopic examinations, immunocytochemical studies, histochemical stains, and electron microscopic studies of concretions obtained from five patients with chronic conjunctivitis. Electron-dense secretory granules, ranging from 0.2 to 0.5 micron in diameter and stained positively for periodic acid-Schiff and mucicarmine, were found in the superficial lining epithelial cells of the pseudogland of Henle. In view of the granular and membranous figures reflecting degenerating epithelial cells and secretory granules in the concretions, we argue that the concretions, are mostly composed of the mucinous secretion of the transformed conjunctival glands admixed with the degenerative products of the epithelial cells.

Multiple enteroliths in a chronically obstructed duodenal loop after Roux-en-Y biliary diversion.

A case of chronic mechanical obstruction of the duodenal loop due to stricturing of the enteroenterostomy after diversion following a Polya gastrectomy for bile reflux gastritis is reported. The dilated loop contained several hundred enteroliths. The clinical and chemical evidence strongly supports the view that the enteroliths were formed in the intestinal loop. This complication of Roux-en-Y reconstruction has not previously been recognized.

Ultrastructure and elemental composition of human pancreatic calculi.

Scanning electron microscopy (SEM) and energy dispersive x-ray fluorescence (EDXRF) have been used in this study to investigate the morphology, nature, and arrangement of major, minor, and trace elements in human pancreatic calculi (PC) obtained from patients with alcoholic and tropical pancreatitis. The present study has confirmed previous observations that PC are rich in CaCO3 (as calcite) and many other elements. Further, we have shown for the first time that the amorphous nidus contained only iron, chromium, and nickel, whereas the outer shell contained calcium and 17 other elements. Based on our studies, we postulate the formation of PC to be taking place in multilayers and multistages. Formation of inner protein nidus in the form of a cobweb is the first stage, then calcite is deposited on this fibrous network as tiny crystals. Because of their high surface area and high surface activity, other metallic ions are incorporated onto it through co-precipitation, adsorption, and/or lattice substitution. This study has further shown that irrespective of the etiology for chronic pancreatitis, the structure and composition of PC are the same suggesting a common pathway for lithogenesis in the pancreatic duct.

Fine structure of the organic matrix of human pancreatic stones.

Pancreatic stones that were removed from the pancreatic ducts of patients with chronic calcifying pancreatitis were decalcified so the organic matrix could be studied by scanning and transmission electron microscopy. The observations made by scanning electron microscopy were compared with those made on undecalcified stones, and the findings were correlated with light microscopic observations. After the calcium carbonate was removed, the stones consisted of multiple partitions arranged like a sponge. They were embedded in a gel-like matrix. The organic partitions frequently were composed of dense surface layers and sparse central reticular accumulations, which had surrounded and bound calcium carbonate crystals. The organic matrix was heterogeneous in texture. Some areas had dense, regular, proteinaceous fibrous material. Deposits resembling fibrin were observed. Altered cellular constituents appeared to make up minor portions of the matrix. Calcium carbonate, which was precipitated in vitro in pancreatic juice, resembled the morphology of pancreatic stones more than that of pure calcium carbonate crystals. These results are consistent with the coformation of pancreatic stones from constituents in the pancreatic juice [including pancreatic stone protein (PSP), glycosaminoglycans, and occasional cells] and precipitated calcium carbonate.

Identification of immunoreactive pancreatic stone protein in pancreatic stone, pancreatic tissue, and pancreatic juice.

We first examined whether pancreatic stone protein (PSP) was present in pancreatic stone and normal pancreatic tissue. By using HPLC and Western blotting, a protein of Mr 13.5 kDa that reacted with monoclonal antibody against PSP was detected as a major component in EDTA-soluble fractions of pancreatic stone. In an in vitro experiment, this protein dose-dependently suppressed CaCO3 precipitation. PSP was immunohistochemically stained in the acinar cells of normal pancreatic tissue. Based on these findings, it seemed that PSP in pancreatic stone is probably a physiological secretory protein of the pancreas. We subsequently examined immunoreactive PSP in normal pancreatic juice by the Western blotting method. In all of the specimens, the band for immunoreactive PSP in pancreatic juice was found to correspond to 13.5 kDa, which thus agreed with that of purified PSP from a stone.

Organic matrix of pancreatic stones associated with nutritional pancreatitis.

In recent studies performed on pancreatic stones from patients with alcoholic pancreatitis, a novel secretory protein was identified: the pancreatic stone protein (PSP Mr 14,000). This protein suppresses CaCO3 precipitation, and could therefore stabilize normally supersaturated pancreatic juice. Crystallographic analysis of stones from patients with nutritional pancreatitis (NP), as well as alcoholic pancreatitis (AP), revealed that the main constituent was calcite (CaCO3). In the present study, we investigated the organic matrix of NP stones. In the 14 cases studied, the organic matrix was rendered soluble after mineral dissolution with EDTA + citrate. Analysis of the isolated matrix revealed the presence of one major protein (Mr 14,000), and of a minor protein (Mr 30,000), which is in fact an aggregate form of the 14,000 Mr protein. Using PSP antibodies, complete immunological identity was found between PSP, the immunoreactive form of PSP present in nonactivated pancreatic juice, and the protein matrix of NP stones. Moreover, protein matrix of NP stones also inhibited the nucleation of CaCO3 crystal, and decreased their growth rate in vitro. The presence of PSP in all AP and NP stones suggests that it plays a key role in stone formation during the course of chronic pancreatitis. These results also suggest the existence of some pathophysiological links between these two apparently different etiological forms of calcifying pancreatitis.

An animal model of pigment cholelithiasis.

Pigment stones of high calcium content were induced in male hamsters of the Harlan Sprague-Dawley strain fed a nutritionally adequate semipurified diet for a period of 14 weeks. The diet contained moderate amounts of cholesterol (0.30 percent) and ethinyl estradiol (15 micrograms/day per animal). At sacrifice, the incidence of pigment stones was 50 percent. When stones were present, they were in the form of numerous black amorphous rods about 0.1 to 0.4 mm in length. Infrared analysis of the dried stones indicated the following composition: calcium phosphate 26.7 percent, calcium bilirubinate 12.8 percent, cholesterol 15.1 percent, and protein 45.4 percent. Pigment stones were associated with an elevated biliary total calcium level (probably induced by the dietary cholesterol) and a paradoxic decrease in the biliary total bilirubin level. The lithogenic diet produced marked elevations in liver and plasma cholesterol levels and cholesterol saturation of bile, but no cholesterol crystals or stones were observed. The accumulation of elevated levels of cholesterol in the livers of the experimental animals produced mild to moderate hepatotoxicity. The precise mechanism of the dietary induction of pigment stones in this hamster model remains to be elucidated.

Urinary mucoprotein in pediatric urolithiasis.

Primary bladder stone is a common pediatric surgical problem in developing countries. Many theories are prevalent. The stone matrix theory is based on increased excretion of its precursor, the uromucoid (the urinary mucoprotein). Uromucoid, studied in urine and stones by the electroimmunodiffusion technique in 49 cases with controls, showed significantly increased excretion in stone cases. Family income and serum protein were the only important influencing factors (negative). Causal relationship between uromucoid excretion, stone matrix, and pediatric bladder stones is discussed. Methylene blue decreased uromucoid excretion but not magnesium oxide, vitamin C or B6 (four common therapeutic drugs for prevention/dissolution of urolithiasis).

Tonsil concretions and tonsilloliths.

Although infrequently seen in many clinical practices, tonsillar concretions can be the source of both fetor oris and physical and social concern for the patient. Though stones rarely form in the tonsil or peritonsillar area, the findings of calcified objects or stones anywhere within the body has long been a subject of interest. The salient features of these entities and their relevance to clinical practice are discussed in this article.

[Pancreatic stone protein, a new marker for chronic pancreatitis]. / La "pancreatic stone protein", un nuovo marker di pancreatite cronica.

A CaCO3 precipitation and crystal growth inhibitor has recently been isolated from pancreatic calculi and from pancreatic juice. It is a glycoprotein with a molecular weight of 14,000, whose probable physiological role is the stabilization of exocrine pancreatic secretion which is normally supersaturated with CaCO3. It is hoped to determine a simple, but sensitive assay of this new protein on pancreatic juice and on serum, a decrease in which could be a marker for chronic pancreatitis.

Pulmonary alveolar microlithiasis with the absence of technetium-99m MDP uptake of lungs.

The authors report a patient with alveolar microlithiasis who was treated for miliary tuberculosis eight years earlier and whose Tc-99m MDP scan revealed absent lung uptake. Diagnosis was established by bronchoalveolar lavage. Both the roentgenogram and computed tomography of the chest confirmed alveolar microlithiasis.

Microlithiasis associated with chronic bronchopneumonia in a cat.

Chronic bronchopneumonia associated with microlithiasis was diagnosed in a 9-year-old domestic shorthair cat with a 3-month history of coughing and dyspnea. Thoracic radiography revealed multifocal patchy alveolar infiltrates in all lung fields. Numerous acellular, concentrically laminated, periodic acid-Schiff-positive microliths were seen in mucus from tracheal washing. Microliths were composed primarily of calcium carbonate. A definite cause could not be identified. There was no response to treatment and the cat was euthanatized. Marked type-II alveolar cell proliferation, peribronchiolar smooth muscle proliferation, and alveolar microlithiasis were seen histologically. Microliths are rarely encountered in tracheal washings from companion animals. Their pathophysiologic properties and meaning remain to be established.

Maxillary antrolith: report of a case.

A case of maxillary antrolith in a 60-year-old male is presented. Complaints were mucous discharge and a small amount of periodic bleeding from the right nasal cavity, of two months' duration. CT scan revealed a small calcified mass in the right maxillary sinus. By Caldwell-Luc operation an antrolith was removed from the right maxillary sinus with chronic sinusitis. This was 0.6 x 0.4 x 0.3 cm in size and 0.03 g in weight. Histopathological studies showed calcium deposition around the necrotic mass. Chemical analysis of the specimen revealed calcium phosphate (65%), calcium carbonate (8%) and albuminous material (27%).

Pathological findings in the bulbourethral glands of bulls.

The bulbourethral glands of 323 Bos indicus or B. indicus crossbred bulls more than 1 1/2 years old were examined in an abattoir study. Bulbourethral adenitis was diagnosed grossly and confirmed by histological examination in 4 (1.2%). Unilateral chronic interstitial inflammation was seen in 2 cases; one of these was associated with a degenerative-type seminal vesiculitis. In the others adenitis was bilateral; in one case it was associated with a concretion and foreign (plant) material in the principal duct of the left bulbourethral gland; in the other bilateral case, numerous calculi were present and microscopically, a chronic active and diffuse inflammation was observed. Chemical analysis of the calculi showed calcium oxalate and tricalcium phosphate to be the most important components. Corynebacterium spp was isolated from the lesion with multiple calculi but attempts to isolate Chlamydia spp, Mycoplasma spp and Brucella abortus from the 4 adenitis cases were unsuccessful. Congenital abnormalities such as glandular fusion (2.2%) or unilateral aplasia (0.6%) were also observed. Cysts were the most common finding (19.2%), and duct dilation was frequent (7.1%). The significance of these findings in relation to fertility is considered.

[A case of obstructive jaundice caused by incarceration of pancreatic stones in the ampulla of papilla Vater].

A very rare case of obstructive jaundice caused by the incarceration of pancreatic stones in the ampulla of papilla Vater is reported. A forty-eight-year-old man, who had been taking alcohol daily for 10 years, was admitted to our hospital because of recurrent attacks of upper abdominal pain. Biochemical analysis demonstrated typical pattern of chronic pancreatitis. US, CT and ERCP showed a markedly dilated pancreatic duct and pancreatic calcifications. Cholecystolithiasis, or dilatation of the choledochus was not noted. Conservative treatment was performed under the diagnosis of chronic calcifying pancreatitis for one month. Then, obstructive jaundice, severe epigastralgia, and high fever occurred. Obstructive jaundice with sudden onset and existence of pancreatic stones suggested incarceration of pancreatic stones in the bile duct, and cephalic pancreaticoduodenectomy was performed. The largest pancreatic stone was incarcerated into the ampulla of papilla Vater. Histopathological analysis of the pancreas showed severe chronic pancreatitis. No report of the similar case can be found in the literature. Incarceration of pancreatic stones into biliary system might be very rare, however, should not be forgotten in differential diagnoses of obstructive jaundice in chronic pancreatitis patients.