Somatostatin inhibits the centrally mediated hypertensive response to clonidine in freely moving rats.

The effect of somatostatin on the hypertensive response induced by intracerebroventricular (i.c.v.) injection of clonidine was investigated in freely moving rats. A 10 micrograms i.c.v. injection of clonidine produced a marked pressor response and a decrease in heart rate. No depressor response was induced by clonidine. The i.c.v. pretreatment with somatostatin (2 and 5 micrograms) dose-dependently inhibited the pressor response to i.c.v. injected clonidine (10 micrograms), and a long-lasting depressor response was observed. Systemic (i.v.) treatment with somatostatin had no such effect. These results suggest that brain somatostatin modulates the centrally-mediated pressor response to clonidine.     

Neurosteroid modulation of dendrodendritic inhibition in the mouse olfactory bulb

The present report describes neurosteroid modulation of olfactory bulb function by examining the effects of intrabulbar infusion of dehydroepiandrosterone sulfate (DHEAS), a neurohormone discovered in rat brain, on field potentials in the granule cell layer evoked by paired-pulse stimulation of the mouse lateral olfactory tract. Infusion of DHEAS (5 nmol) significantly decreased the test response without affecting the conditioning response. As a consequence, DHEAS selectively potentiated paired-pulse depression, which is believed to be due to granule cell-mediated inhibition of the mitral/tufted cells. The granule-to-mitral/tufted dendrodendritic synapse is GABAergic. Taken together, these results suggest that DHEAS potentiates the GABAergic dendrodendritic inhibition exerted by the granule cells on the mitral/tufted cells.     

Natural antibodies against the immunoglobulin F(ab′)2 fragment cause elimination of antigens recognized by the F(ab′)2 from the circulation

A humanized monoclonal IgG1 antibody, designated hC4G1, recognizes the fibrinogen receptor glycoprotein (GP)IIb/IIIa on platelets and inhibits platelet aggregation. When the F(ab′)₂ fragment of hC4G1 (F(ab′)₂ hC4G1) was administered to cynomolgus monkeys, all the monkeys showed inhibition of platelet aggregation ex vivo. Unexpectedly, a significant decrease in platelet count was observed in 5 of 18 monkeys. Antibodies against F(ab′)₂ hC4G1 were detected in the plasma of these monkeys by ELISA. Antibody activity in the plasma of these monkeys was significantly correlated with the intensity of platelet decrease (r = 0.84). The natural monkey antibodies to F(ab′)₂ hC4G1 were directed against the C-terminal region of F(ab′)₂ fragment common to all human and humanized IgG antibodies. Natural homo-reactive antibodies were also detected in human plasma from 15 of 40 healthy volunteers. Specificity was closely similar to that of the monkey antibodies. Affinity-purified human homo-reactive antibodies enhanced phagocytosis of platelets treated with the F(ab′)₂ hC4G1. Monkey plasma with high homo-reactive antibody activity was confirmed to decrease platelet count when administered together with F(ab′)₂ hC4G1 to a monkey with low antibody activity. These results suggest that F(ab′)₂ of humanized and human antibodies causes elimination of the corresponding antigens from the circulation by homo-reactive antibodies.     

Chemical and biological properties of a peptidoglycan isolated from Treponema pallidum kazan.

A peptidoglycan layer of Treponema pallidum kazan was isolated by solubilization of whole cells with 1% warm sodium dodecyl sulfate and subsequent digestion of an insoluble residue with proteases. Electron microscopy revealed that the peptidoglycan was isolated as a single-layered sacculus of less than 5 nm in thickness, freed from axial filaments and an envelope sheath. An isolated peptidoglycan fraction was mainly composed of glucosamine, muramic acid, alanine, glutamic acid, ornithine, and glycine in molar ratios of 0.65:0.68:1.63:1.00:0.75:1.03. Amino (N)- and carboxyl (C)-terminal amino acid analyses suggested the involvement of at least a part of the glycine residue in cross-linking between the amino group of ornithine residue at one strand of the stem peptide subunit and the carboxyl group of alanine of the neighboring strand. The treponemal peptidoglycan lacked the immunoadjuvant activity both to stimulate antibody production and to induce delayed-type hypersensitivity against ovalbumin, as well as the properties necessary to stimulate guinea pig and mouse splenocytes and guinea pigs peritoneal macrophages, unlike the cell walls or peptidoglycans (group A type of Schleifer and Kandler's classification, Bacteriol. Rev. 36:407-477, 1972) isolated from many bacterial species parasitic to the mammal. However, the peptidoglycan activated the human complement system through the alternative pathway, as well as the classical one, and caused a liberation of 5-hydroxytryptamine in rabbit blood platelets in a similar manner to the cell wall peptidoglycans of both group A and B types.     

BOVINE SERUM ALBUMIN (BSA) NEPHRITIS IN RATS IV. A SEQUENTIAL EVALUATION OF MONONUCLEAR PHAGOCYTE SYSTEM (MPS) FUNCTION

A clearance kinetic study of intravenously administered ¹²⁵I-labeled aggregated human IgG (¹²⁵I-AHIgG) from the circulation and its distribution in various organs was performed weekly during the course in a model of experimental immune complex glomerulonephritis which was induced in rats immunized 8 weeks previously with 6 times a week administration of 2 mg of bovine serum albumin (BSA) for 4 weeks from week 8 to 12. The removal rates of the injected ¹²⁵I-AHIgG from the circulation were retarded in nonproteinuric rats of week 9 and 10, at almost every checked point (p-value was <0.01). The clearance in those rats with severe proteinuria returned to the level of the control and of rats in week 8. The distribution of ¹²⁵I-AHIgG in the liver 4 hours after the administration revealed a considerable decrease in non-overt proteinuric rats of weeks 9, 10, and 11. A similar tendency of decreasing depositions of the radioactivity was shown in the spleen at each 4 hours. In contrast, the uptakes in the kidney and lung at the final week of 12 were larger. Delayed clearance from the circulation and a decreasing handle of the injected macromolecule in the liver and possibly in the spleen may suggest the presence of some impairment of the MPS function in the course of this experimental glomerulonephritis.     

Hyperosmolarity response of ocular standing potential as a clinical test for retinal pigment epithelium activity normative data

The standing potential of the eye is decreased by intravenous administration of hypertonic solutions. This hyperosmolarity-induced response has been recorded in normal subjects by the use of electro-oculography (EOG) in the dark. An intravenous administration of Fructmanit^® (1.4 × 10³ mOsmol) (150 500ml, 2.37 9.70ml/kg, 0.08 0.36 ml/kg/min) was used to evoke the hyperosmolarity response. The amplitude of the response was expressed in percentage, V₀ – V_min/V₀ × 100, where V₀ is the base value of the EOG before administration of the hypertonic solution and V_min is a minimum EOG amplitude after administration. The distribution of the amplitude of the hyperosmolarity response was approximated by the normal distribution in normal subjects. The minimum, the maximum, the mean and the standard deviation of the amplitude of the hyperosmolarity response were respectively 34.2%, 52.3%, 42.6% and 4.6% in normal subjects. The normal range of the hyperosmolarity response would be 33.4 51.8% (M ± 2SD). The hyperosmolarity response, which originates mainly in the retinal pigment epithelium, is a useful new quantitative and specific test of the activity of the retinal pigment epithelium in clinical practice.     

Hyperosmolarity response of ocular standing potential as a clinical test for retinal pigment epithelium activity rhegmatogenous retinal detachment

The hyperosmolarity response of the ocular standing potential was recorded in unilateral rhegmatogenous retinal detachment (8 eyes) and in the fellow healthy eye (8 eyes). The hyperosmolarity response was greatly suppressed (M-4 SD: M and SD indicate respectively the mean and the standard deviation in normal subjects) in all affected eyes (p < 0.005), and slightly abnormal in 2 fellow eyes. The L/D ratio was normal in 2 affected eyes and in all fellow eyes. The hyperosmolarity response in the affected eyes was still greatly suppressed 14 months after successful surgical treatment.     

Quantitative cell and matrix changes in human humeral head osteoarthritic cartilage

A new quantitative method was devised both to establish an objective standard for morphometric diagnosis and to determine the extent of degeneration in osteoarthritic cartilage. Eight normal and forty-eight osteoarthritic humeral heads, subsequently confirmed by light microscopy, were obtained at necropsy. The articular cartilage was observed in situ with a laser scanning confocal microscope (LSCM) and morphometric measurements determined cell density (cells/mm), cell volume fraction (%) and mean cell volume (microm3). The osteoarthritic cartilages were classified according to the following four characteristics: increase in thickness, increase in cell volume fraction, decrease in cell volume fraction, and fibrous pannus. Deviations in cell density and cell volume fraction from normal means were calculated as extent of degeneration. Our present approach aims to provide valuable clues, such as objective stereological information and a unique reference for biochemical and traditional morphological analyses, that clinicians will be able to use in combination with other methods in order to establish a reliable diagnosis.     

Unilateral Multicentric Breast Carcinoma Studied by Whole Mammary Gland Serial Sectioning

The incidence and clinicopathologic features of unilateral multicentric breast cancer (UMBC) were studied by mammary gland serial sectioning in 116 cases of clinically defined monocentric breast cancer (MONBC) examined histopathologically at the Nagano Cancer Detection Center. UMBC was defined as: 1) histopathologically discontinuous tumors each with an intraductal spread, 2) at least one tumor-free section separating two tumors, and 3) a large primary tumor and other small secondary tumors. UMBC was detected in 23 of 116 cases (19.8%), all with one secondary tumor. Primary and secondary tumors were located in the same quadrant in 34.8% and in different ones in 65.2%. The secondary tumors were <5 mm in size in 56.5%. Secondary tumors, averaging 8.3 mm in size and 25.5 mm in distance from the primary tumor, were almost exclusively noninvasive carcinomas, including 15 (65.4%) noninvasive ductal carcinomas and several special types. The primary and secondary tumors were of the same histologic type in 3 of 23 cases. UMBC patients averaged 6 years younger than MONBC patients, and the incidence of UMBC tended to be higher in younger patients (p<0.1). UMBC tended to occur more frequently in quadrant with an average histologie tumor size significantly smaller than that in MONBC (p<0.01). The histologie types of the primary tumor in UMBC and MONBC were similar, with common types predominant. Lymph node metastases tended to be slightly more frequent in MONBC. This high incidence of UMBC calls for careful attention when considering breast conserving therapy.