Search

Tooth is a composite of the three different biological mineralized tissues (dentin, enamel, and cementum) that acquired supreme mechanical properties and function necessary for the mechanical digestion of the food throughout life. The underlining mechanisms of mineralization of each of these three components are unique and different from each other. Here the focus was placed on the mineralization process of dentin and enamel of the teeth of vertebrates.

Vibrio vulnificus is an opportunistic human pathogen causing wound infection and septicemia, characterized by hemorrhagic and edematous damage to the skin of limbs. When injected into the dorsal skin, an extracellular metalloprotease from this vibrio (V. vulnificus protease: VVP) enhanced the vascular permeability through activation of the Hageman factor-plasma kallikrein-kinin cascade and/or stimulation of exocytotic histamine release. Additionally, VVP caused the hemorrhagic skin lesion through disorganization of the vascular basement membrane layer due to specific degradation of type IV collagen, which is known to form the backbone structure of the basement membrane. However, injected VVP was quickly inactivated by a plasma glycoprotein, alpha-macroglobulin, at a molar ratio of 1:1. This glycoprotein was leaked from the capillaries by the actions of VVP, which resulted in in situ inactivation by physical entrapment. When VVP (45,000 Da) was incubated at 37 degrees C, a 35,000 Da fragment was generated by the autocatalytic removal of a 10,000 Da C-terminal polypeptide. This N-terminal fragment showed significant proteolytic activity, however, because of a markedly decreased affinity to the protein substrates, its permeability-enhancing and hemorrhagic activity was reduced to less than 50%. These findings indicate that the C-terminal polypeptide is not essential for but promotes skin reactions caused by VVP.

We reviewed the recent advances in the molecular characterization of prostanoid and bradykinin receptors. Prostanoids and bradykinin exert versatile actions in diverse tissues and cells through specific cell surface receptors. Molecular biological studies revealed the primary structure of eight types and subtypes of prostanoid receptors from various species. These include the thromboxane A2 receptor, prostacyclin receptor, prostaglandin (PG) F receptor, PGD receptor and four subtypes of PGE receptor (EP1, EP2, EP3 and EP4). There are four subtypes of bradykinin receptor (BK1, BK2, BK3 and BK4), but it is still unknown about the detail of BK3 and BK4. These results also have achieved the remarkable development in the field of human hypertension.

In order to clarify endocrinological changes before and after living-related renal transplantation in a patient of Bartter's syndrome involving chronic renal failure, serial quantitative determinations of the renin-angiotensin-aldosterone system and 24-hour urinary excretion of 6-keto-prostaglandin F1 alpha and kallikrein were performed. A male patient was admitted to hospital because of a pale face and short stature at the age of 13 years. He was 126 cm in height (M-3.8SD). Blood pressure was 110/60 mmHg and edema was not observed. Laboratory findings showed that his hematocrit was 22.1%, serum potassium 2.9 mEq/1, creatinine clearance was 30.7 ml/min/1.73m2 and beta 2-microgobulin was elevated to 39.9 mg/1 in urinalysis. Plasma renin activity and aldosterone were remarkably elevated to 24.23 ng/ml/hr and 738 pg/ml, respectively. The kidney biopsy specimen showed diffuse glomerulosclerosis and hypertrophic change of the juxtaglomerular apparatus was also demonstrated. He was diagnosed as Bartter's syndrome with short stature and chronic renal failure. At the age of 18, he was introduced on hemodialysis and the living-related renal transplantation was performed the next year. Two weeks after the transplantation, plasma renin activity, angiotensin, I,II and aldosterone were markedly changed from 37.8 to 2.3 ng/ml/hr, 2400 to 220 pg/ml, 256 to 17 pg/ml and 3700 to 110 pg/ml, respectively. Urine prostaglandin F 1 alpha was improved from 860 to 321 ng/day and kallikrein was also changed from 400 to 25.2 micrograms/day. These results indicated that abnormalities of several hormones in Bartter's syndrome could be normalized by living-related renal transplantation.(ABSTRACT TRUNCATED AT 250 WORDS)

This study showed that nasal allergy patients have increased nasal airway resistance and tissue kallikrein activity in nasal lavage in accordance with the severity of symptoms. Nasal airway resistance and tissue kallikrein activity were significantly increased in the nasal lavage collected 15 min after antigen challenge, placement of a disk containing house dust antigen. The free kinin level in the nasal lavage collected 15 min after the antigen challenge was also markedly increased. Pretreatment of patients with d-chlor-pheniramine maleate (histamine H1 receptor antagonist) blunted this increase in nasal airway resistance and tissue kallikrein activity 15 min after the antigen challenge, suggesting that histamine may accelerate excretion of tissue kallikrein in nasal secretions. Camostat mesilate inhibited the in vitro tissue kallikrein activity in nasal lavage collected from allergy patients. Administration of camostat mesilate significantly inhibited nasal airway resistance and tissue kallikrein activity in nasal lavage after the antigen challenge, indicating that kinin generated in the nasal cavity increased nasal airway resistance. These results suggest that tissue kallikrein inhibitors may serve as anti-allergic drugs by suppressing the nasal symptoms of nasal allergy patients.

The renal kallikrein-kinin system seems to participate in the regulation of blood pressure, control of sodium and water excretion, renal vascular resistance and renin release. By using ultrastructural immunocytochemistry, in situ hybridization or polymerase chain reaction experiments with the appropriate cDNA probes, kallikrein and kininogen were observed to exist and be synthesized in different types of cells of the nephron. Recently, new finding of a kinin receptor has been reported, since specific kinin receptor antagonists have become available. The localization of components of kallikrein-kinin system in the kidneys and its relation to renal function is discussed.

The posterior stomach was isolated from each male Donryu rat and separated into two parts: the tunicae mucosa and submucosa and the tunicae muscularis and serosa. Active and inactive tissue kallikrein were measured using sandwich type enzyme linked immunosorbent assay (s-ELISA) and H-Pro-Phe-Arg-MCA to complement each other. Inactive tissue kallikrein was determined (1) by measuring total tissue kallikrein and active tissue kallikrein in trypsin-treated samples and trypsin-nontreated ones, respectively; and (2) by subtracting active tissue kallikrein from total tissue kallikrein. Although tissue kallikrein was not demonstrable in the tunicae muscularis and serosa, inactive tissue kallikrein in the tunicae mucosa and submucosa reached 79.6% with s-ELISA and 99.1% with H-Pro-Phe-Arg-MCA. Water-immersion stress significantly decreased total tissue kallikrein at Stage IV of ulcers compared with the control value (p less than 0.001 in both measuring methods). Immunohistochemical staining was made using the avidin-biotin-horseradish peroxidase complex method. Tissue kallikrein was proved to be diffusely present as the inactive type within the epithelial cells of the pits in the gastric mucosa of the normal rats. With the progress of ulcers, however, it disappeared from the cells and appeared in the intercellular space. At Stage IV, it began to disappear even from the intercellular space. Based on the previously proposed process of tissue kallikrein release into blood in man, a possible interpretation of the above findings is that inactive tissue kallikrein may serve to maintain the gastric mucosa in a normal state; and that it may be transformed into the active type with ulceration and eliminated in a form of complex with some protease inhibitor in the course of aggravation.

Tissue kallikrein could be specifically demonstrated in the human gastric mucosa using sandwich-type enzyme-linked immunosorbent assay. Eighty-five patients with chronic gastritis were then studied to investigate the relationship of tissue kallikrein to endoscopic and pathologic findings. The endoscopic Congo red method was used to classify the atrophic pattern of each patients gastric mucosa into the normal, closed or open type. Tissue kallikrein increased significantly in the closed type compared with the normal type (P less than 0.01) and in the open type compared with the closed type (P less than 0.001). Pathological findings were classified into three groups: (A) normal surface epithelium, with slight infiltration by inflammatory cells; (B) atrophic surface epithelium, with marked infiltration by inflammatory cells; and (C) atrophic surface epithelium, with marked infiltration by inflammatory cells and intestinal metaplasia. Tissue kallikrein significantly increased in the B group compared with the A group (P less than 0.01) and in the C group compared with the B group (P less than 0.001). Tissue kallikrein markedly increased with the appearance of intestinal metaplasia in the open type rather than in the closed type. An immunohistological study demonstrated that tissue kallikrein was present in the cells showing intestinal metaplasia and goblet cells. These findings suggest that chronic gastritis is a process of reconstruction of gastric mucosa.

In order to evaluate the effect of the angiotensin I-converting enzyme inhibitor, captopril, on lipid metabolism, we measured serum lipoperoxides concentration ( LPX ) as well as plasma levels of renin activity (PRA), aldosterone (PAC) and bradykinin ( PBK ) before and after captopril administration in 15 hypertensive patients. Captopril significantly lowered the LPX (p less than 0.05 by repeated measures ANOVA) from the control value of 3.25 +/- 1.16 (mean +/- S.D.) to 2.92 +/- 0.94, 2.83 +/- 1.10, and 2.89 +/- 1.31 nmol/ml 30, 60, and 120 min after the administration, respectively. A significant reduction of blood pressure (p less than 0.0001) and PAC (p less than 0.01) was observed following captopril administration, while PBK increased significantly (p less than 0.001) from a baseline level of 10.85 +/- 4.07 to 13.95 +/- 5.29, 16.25 +/- 6.85, and 15.71 +/- 7.65 pg/ml 30, 60, and 120 min after captopril administration, respectively. There was no significant correlation between changes in serum LPX and in mean blood pressure, PRA and PAC, though a significant inverse relationship was found between changes in serum LPX and in PBK 120 min after the administration (r = -0.576, p less than 0.05, n = 13). Although the mechanisms by which serum LPX is decreased by captopril are not clear, it is suggested from the results that captopril is a beneficial antihypertensive agent for preventing LPX -induced atherosclerosis in hypertensive patients.

In this study, urinary kallikrein quantity and activity were measured by the kallikrein direct RIA and kininogenase activity with human low molecular weight kininogen in 32 non pregnant healthy women and 20 normal 3rd trimester pregnant women. There was no significant difference in urinary kallikrein quantity between non pregnant healthy women (n=32, 64.0 +/- 6.3 micrograms/day, mean +/- S.E.) and normal pregnant women (n=20, 68.1 +/- 10.1 micrograms/day). There was a significant difference (p less than 0.05) in urinary kallikrein activity between non pregnant healthy women (n=32, 496.2 +/- 57.2 micrograms kinin/day) and normal pregnant women (n=20, 319.5 +/- 48.1 micrograms kinin/day). The reason for no significant difference in the urinary kallikrein quantity may be that neither non pregnant women nor normal pregnant women have renal damage. And, one of the reasons for significant low urinary kallikrein activity in normal pregnant women may be that the sensitivity of blood vessels to angiotensin II in normal pregnancy is less than in non pregnancy.

The effects of sympathetic nerve stimulation and administrations of sympathomimetics on the secretion of salivary kallikrein induced by stimulation of Chorda tympani were examined quantitatively and qualitatively in the dog submandibular gland. Both sympathetic stimulation and administrations of sympathomimetics such as norepinephrine, epinephrine, and isoproterenol caused increased secretion of salivary kallikrein. Among these effects, those of the sympathetic stimulation, norepinephrine, and epinephrine were not completely abolished by pretreatment with phenoxybenzamine or propranolol, but the effect of isoproterenol was abolished by pretreatment with propranolol, and was hardly influenced by pretreatment with phenoxybenzamine. From these results, it would appear that secretion of salivary kallikrein may be mediated through adrenergic alpha- and beta-receptors. On the other hand, in contrast with the activities of the salivary kallikrein secreted by Chorda tympani stimulation or administration of isoproterenol which were not inhibited by SBTI, the activities of the salivary kallikrein secreted by sympathetic stimulation as well as administration of norepinephrine or epinephrine were markedly inhibited by SBTI. From these results, it is concluded that secretion of glandular kallikrein is due either to Chorda tympani stimulation or is mediated through adrenergic beta-receptor, while secretion of plasma kallikrein is mediated through adrenergic alpha-receptor.

The aim of the study is to clarify the role of the kinin forming system on ovulation. The results were as follows, Plasma prekallikrein of superovulated prepubertal rats was decreased to 50-60% of the normal level after PMS injection and 80-90% of the normal level after hCG injection. The lowest level was 33.8% 39 hours after PMS injection. Aprotinin suppressed the superovulation of prepubertal rats at doses of 16.7 X 10(4) KIE and 37.8 X 10(4) KIE (p less than 0.01). These results showed that the kinin production system has an effect on ovulation. As the sex steroid hormone, estradil benzoate, progesterone and testosterone propinate were used in oophorectomized mice. They had no effect on the plasma prekallikrein level. The plasma prekallikrein level during the estrus cycle of mature female mice was 85.5% of the control level in preestrus, 80.3% in estrus, 83.7% in metestrus and 89.8% in diestrus. The mean was 83.9%, which was significantly lower than that for oophorectomized mice (94.1%). It is proved that plasma prekallikrein was consumed and the kinin forming system was accelerated in the ovary with ovulation.

A radioimmunoassay was performed for direct measurement of urinary active and trypsin-activatable inactive kallikreins excretion in 34 patients with Type II diabetes mellitus. (1) Diabetics showed slightly low total (inactive plus active) kallikrein excretion, normal inactive kallikrein excretion and significantly low active kallikrein excretion and active-to-total kallikrein ratio. (2) Total kallikrein excretion was normal in normotensive diabetics and hypertensive diabetics without nephropathy, low in hypertensive diabetics with nephropathy. Active kallikrein excretion and active-to-total kallikrein ratio in hypertensive diabetics were remarkably low regardless of nephropathy. (3) Para amino hippurate clearance correlated with total kallikrein excretion in normal subjects and, with active kallikrein excretion and active-to-total kallikrein ratio in both normal subjects and diabetics, but not with total kallikrein excretion in diabetics. Creatinine clearance did not correlate with total, inactive kallikrein excretions and active-to-total kallikrein ratio. (4) A positive correlation was found between fractional sodium excretion and active kallikrein excretion in normal subjects, but not in diabetics. The results suggest that reduction in ratio of active-to-total kallikrein by renal dysfunction might decrease sodium excretion in diabetics with nephropathy.