Renal sodium transport abnormality: Gitelman's syndrome and renal sodium transporter

Recent studies using molecular biological methods have enabled us to identify the genetic abnormality in renal electrolyte metabolism. In renal tubules, diuretic sensitive Na transporter systems are present, and key molecules have been cloned. Thiazide-sensitive Na-Cl contransporter (TSC) is one of the molecules localized in the distal convoluted tubule, whose genetic abnormality causes Gitelman's syndrome (a variant of Bartter's syndrome characterized by dehydration, hypokalemic metabolic alkalosis, secondary aldosteronism lacking hypertension, hypomagnesemia, and hypocalciuria). We identified a mutation in TSC (Leu to Pro change at 623 amino acid position, L623P) in familial Gitelman's syndrome, and we confirmed the loss of TSC function by this mutation in a functional expression system using mammalian cells. This L623P mutation has been found in other patients with Gitelman's syndrome living in the northern part of Japan.     

Mucosal gastrin receptor. V. Development in newborn rats

We determined the development of the oxyntic gland mucosal gastrin receptor in rats killed at various times from 5 to 60 days after birth. Rats were weaned on the 18th day after birth. Newborn animals had no detectable gastrin binding, high serum gastrin levels (800-1,200 pg/ml), low antral gastrin levels (0.5-2.0 micrograms/g tissue), or high pH of gastric contents (pH greater than 5.0) and did not respond to pentagastrin. At the time of weaning, serum gastrin dropped to 600 pg/ml and reached adult levels (300 pg/ml) on day 40. Antral gastrin increased to 7.5 micrograms/g tissue on day 20 and reached adult levels (20 micrograms/g tissue) on day 22. Specific binding of gastrin was first detected on day 20 and reached the adult level of 4 fmol/mg protein on day 60. Pentagastrin significantly stimulated acid secretion on day 20 and DNA synthesis on day 25. Prevention of weaning through day 25 decreased the magnitude but did not prevent or delay the onset of the above changes. These results indicate that 1) the absence of a gastrin response in newborn rats is due to a lack of gastrin receptors, 2) development of gastrin receptor and biological sensitivity to gastrin appear at the time of weaning, and 3) the development that occurs with weaning is enhanced but not triggered by the shift to solid food.     

Continuous estimation of systolic blood pressure using the pulse arrival time and intermittent calibration

A continuous noninvasive method of systolic blood pressure estimation is described. Systolic blood pressure is estimated by combining two separately obtained components: a higher frequency component obtained by extracting a specific frequency band of pulse arrival time and a lower frequency component obtained from the intermittently acquired systolic blood pressure measurements with an auscultatory or oscillometric system. The pulse arrival time was determined by the time interval from QRS apex in electrocardiogram to the onset of photoplethysmogram in a fingertip beat-by-beat via an oximetric sensor. The method was examined in 20 patients during cardiovascular surgery. The estimated values of systolic blood pressure were compared with those measured invasively using a radial arterial catheter. The results showed that the correlation coefficients between estimated values and invasively obtained systolic blood pressure reached 0.97±0.02 (mean±SD), and the error remained within ±10% in 97.8% of the monitoring period. By using a system with automatic cuff inflation and deflation to acquire intermittent systolic blood pressure values, this method can be applicable for the continuous noninvasive monitoring of systolic blood pressure.     

Role of prostaglandin E receptor subtypes in gastroduodenal HCO3- secretion

Gastroduodenal HCO3- secretion is a key process that aids in preventing acid-peptic injury. Endogenous prostaglandins (PGs) play a particularly important role in the local control of this secretion. The secretion of HCO3- in both the stomach and duodenum was increased in response to PGE2 as well as mucosal acidification, the latter occurring with concomitant enhancement of mucosal PG generation. These HCO3- responses in the duodenum were markedly reduced by prior administration of the EP4 antagonist in rats, and profoundly decreased in the animals lacking EP3 receptors but not EP1 receptors. In contrast, gastric HCO3- responses induced by PGE2 and mucosal acidification were prevented by the EP1 antagonist and disappeared in EP1, but not EP3-knockout mice. Consistent with these findings, duodenal HCO3- secretion was stimulated by both EP3 and EP4 agonists but not EP1 or EP2 agonists, while gastric HCO3- secretion was increased by the EP1 agonist but not EP2, EP3 or EP4 agonists. In addition, the HCO3- stimulatory action of sulprostone (EP1/EP3 agonist) in the stomach was inhibited by the Ca2+ antagonist verapamil but not affected by IBMX, the inhibitor of phosphodiesterase, while that in the duodenum was inhibited by verapamil and enhanced by IBMX. Forskolin, the stimulator of adenylate cyclase, increased HCO3- secretion in the duodenum but not the stomach. Thus, the HCO3- stimulatory action of PGE2 in the duodenum is mediated by both EP3 and EP4 receptors being coupled intracellularly with both Ca2+ and cAMP, while that in the stomach is mediated by EP1 receptors, coupled with Ca2+.     

Met72Thr polymorphism of pigment epithelium-derived factor gene and susceptibility to age-related macular degeneration

Age-related macular degeneration (ARMD) is the most common cause of acquired blindness among the people of occupational age. Although the pathogenesis of ARMD is not fully understood, several studies suggest a possible contribution of a genetic factor in the development and progression of ARMD. Pigment epithelium-derived factor (PEDF), a glycoprotein that belongs to the superfamily of serine protease inhibitors, was first purified from the conditioned media of human retinal pigment epithelial cells as a factor with potent neuronal differentiating activity in human retinoblastoma cells. Recently, PEDF has been shown to be a highly effective inhibitor of angiogenesis in cell culture and animal models. In addition, PEDF has been found in the vitreous, and its levels were decreased in angiogenic eye diseases, thus suggesting that a loss of PEDF in the eye is functionally important in the pathogenesis of ARMD. A functional amino acid change, a methionine to threonine polymorphism (Met72Thr polymorphism) at codon 72 in exon 3 (T/C polymorphism) of the PEDF gene, that results in the formation of BsstSI restriction site, has recently been identified. Since it is well known that a single nucleotide polymorphism and resultant amino acid change often alters the activity or expression level of the target protein, we would like to propose here a novel hypothesis that the Met72Thr polymorphism (T/C polymorphism) of PEDF gene may be a genetic marker for ARMD. Are genotype and allele frequencies of the Met72Thr polymorphism (T/C polymorphism) different between the patients with or without ARMD? Is this polymorphism associated with disease severity and progression? If the answer is yes, does this Met72Thr polymorphism regulate the vitreous levels of PEDF? These clinical studies could provide us with information whether this genetic variant of the PEDF gene could present an attractive candidate susceptibility gene for ARMD.     

Localization of motoneurons innervating the posterior belly of the digastric muscle: a comparative anatomical study by the HRP method.

Motoneurons innervating the posterior belly of the digastric muscle were identified in the monkey, cat, dog, guinea pig and rat by the HRP method. After injections of horseradish peroxidase (HRP) into the posterior belly of the digastric muscle, two groups of HRP-labeled motoneurons were observed; the rostral group was seen as a small cluster of neurons in the lateral reticular area along the medial border of the descending root of the facial nerve, and the neurons of the caudal group were distributed among the ascending root fibers of the facial nerve. The distribution pattern of these neurons corresponded to that of the accessory facial nucleus neurons. The accessory facial nucleus was lacking in the rabbit in which the posterior digastric (PD) muscle is nonexistent.     

Epstein-Barr virus-related Hodgkin's disease showing B cell lineage in an immunosuppressive patient seropositive for HTLV-I

A case of Hodgkln's disease (HD), lymphocyte depression (LD) type In an Immunosuppressive patient is described. The patient was a 48-year-old male and his parents were born In the Kyushu area, which is an endemic area for adult T cell lymphomaheukemla (ATL). He was seropositive for ATL virus (ATLV, also referred to as HTLV-I) and showed a marked Immunosuppressive condition. He developed LD-HD and Pneumocystis carinii pneumonia, and died due to respiratory failure. The Immunohistochemical and in situ hybridization analyses revealed that the Reed-Sternberglike cells In the lymph node biopsy sample were positive for Ber-H2 (CD30), Leu-M1 (CD15), L-26 (CD20), Bcl-2, p53 and EBER, the viral genome of Epstein-Barr virus (EBV).     

THE BEHAVIOUR OF LYMPHOGENEOUSLY GIVEN ANTIGEN IN THE LYMPH NODE THE LOCALIZATION OF GIVEN ANTIGEN and NEWLY FORMED ANTIBODY

The vascular structures in the lymph node and their relation to fluid exchange have been reported in previous communications and it was considered that the morphological changes of the vascular structures were closely correlated with the functional development of lymph nodes as an antibody forming organ. In order to clarify the localization of the given antigen and newly formed antibody in relation to the morphological structure of lymph nodes, the popliteal lymph nodes of rabbits were studied by immuno-fluorescent techniques.
The antibody was found in the pavement arrangement (solid) of reticulum tissue which was formed by the expel of lymphocytes in the cortical mass and by the morphofunctional alterations of the reticulum cells. The given antigen and newly formed antibody were never detected in the follicles throughout the period of this experiment. ACTA PATH. JAP. 22:427–440, 1972.