Preeclampsia related to a functioning extrauterine placenta: report of a case and 25-year follow-up.

We report the case of a patient with preeclampsia due to an extrauterine, intra-abdominal pregnancy. After the fetus was delivered, but while the functioning placenta remained in the abdomen, preeclampsia, which was documented by clinical data and a kidney biopsy, persisted until the placenta was removed 99 days postpartum. A kidney biopsy 21 months postpartum was normal. Twenty-five years later, her kidney function and blood pressure were normal. The observation of this patient supports the view that the placenta must be intact for the development of preeclampsia and is the first description of endotheliosis in a kidney biopsy from a hypertensive woman with an intra-abdominal pregnancy.

Mast cells and calcium in severe uremic itching.

Mast cells may be more abundant in the tissues of uremic patients and may contribute to itching via mediator release. Because mast cell (MC) granule release may be inhibited by ultraviolet B (UVB) radiation, we investigated skin MC in the superficial dermis by quantitative histomorphometry before and after whole body UVB for uremic itching. Toluidine blue-stained 3.5 mm punch biopsy specimens were examined with a micrometer grid after separate coding. Upon entry to the study, itching dialysis patients indicated their itching intensity on a visual analog scale (0 to 10). Concurrent study of living, related kidney donors (controls, n = 11) and their recipients (n = 11) showed no differences in MC number per unit area. Compared to controls, skin MC number was not greater in itching dialysis patients (n = 20). MC number decreased after 2 months of UVB from 1.6 +/- 0.6 (standard deviation) to 1.0 +/- 0.7 (n = 11, p = 0.025). Pre-UVB total plasma calcium correlated directly with itching intensity, but not with MC number. Plasma phosphate and intact parathyrin level were not statistically related to itching or MC number. Of the 14 subjects that completed UVB, 8 had objective benefit, and mean itching intensity declined from 7.1/10 to 5.2/10 in the 14 subjects. The conclusion is that although skin MC number may decline with chronic UVB, MC number is not related to uremic itching, and hypercalcemia, but not elevation of parathyrin or plasma phosphate, relates statistically to severe uremic itching.

Histopathologic changes in snoring and obstructive sleep apnea syndrome.

The pathophysiologic events that lead to the loss of airway compensation in obstructive sleep apnea (OSA) are poorly understood. The development of airway instability may be secondary to changes in neurologic control, airway morphology, or both. To identify potential histopathologic features of pharyngeal tissues that may contribute to OSA, transverse sections of the distal soft palate and uvula were qualitatively compared using light and electron microscopy from 4 severe apneics (greater than 50 apnea/hour), 4 severe snorers (less than 20 apnea/hour), and 4 nonsnorers. Light microscopy of both apneics and snorers revealed mucous gland hypertrophy with ductal dilation and focal squamous metaplasia, disruption of muscle bundles by infiltrating mucous glands, focal atrophy of muscle fibers, and extensive edema of the lamina propria with vascular dilation. Severe snorers did not differ qualitatively from apneics in the characteristic changes found; however, some snorers had less extensive changes. No distinctive histopathologic findings could be associated with the development of apnea. Electron microscopy of severe apneics identified frequent focal degeneration of myelinated nerve fibers and axons. The finding of similar histopathologic changes in apneics and severe snorers supports previous speculation of a common etiology not directly related to apnea, such as vibratory trauma to pharyngeal tissues. Degenerative changes in peripheral nerves, identified on electron microscopy, however, may contribute to airway instability and the development of obstructive apnea by impairing pharyngeal reflexes.

Effects of enteric neural defunctioning on small bowel motility.

In this study, we investigated the role of intrinsic nerves of the small intestine on phase III migration of the migrating myoelectric complex. Fasting myoelectric activity was recorded from the small bowel in chronically instrumented dogs. Once control experiments were completed, the animals were divided into two groups and were reoperated. In the first group of five dogs, a 1.5-g/dl aqueous solution of cobaltous chloride (shown to induce degeneration of intestinal intrinsic nerves) was infused close intra-arterially to perfuse a 15-cm segment of jejunum. In the second group of dogs, a catheter was implanted in a branch of the superior mesenteric artery supplying a 15-cm segment of intestine. Tetrodotoxin (0.3-1 micrograms/kg) was infused through the catheter just before the arrival of phase III activity in the perfused segment. Subsequent to the fifth postcobalt perfusion day, phase III traversed but did not occur in the cobalt-treated segment. When tetrodotoxin was injected through the catheter, spontaneous phasic myoelectric and contractile activities in the perfused jejunal segment were inhibited, but phase III migration was not blocked. These findings suggest 1) acute or chronic defunctioning of enteric nerves does not interrupt phase III migration, but 2) phase III expression is dependent on the integrity of intrinsic nerves.

Chemical degeneration of intestinal nerves.

In 15 dogs, cobalt chloride solutions were infused close intra-arterially to perfuse a short segment of the jejunum. In an additional four dogs, the jejunum was perfused with the aqueous vehicle (perfusion control). All animals were killed after 1 mo and tissue samples from cobalt-treated and from nonperfused intestine (tissue comparison control) were obtained for electron microscopic and immunohistochemical studies. Segments infused with 0.25 g/dl cobalt solution showed minimal changes; the most striking feature was an increase of vasoactive intestinal polypeptide (VIP)- and substance P-containing neurosecretory granules. Cobalt chloride at higher concentrations (0.75-1.5 g/dl) induced degeneration of ganglion cells and axons in both the myenteric and submucosal plexi. In contrast, the smooth muscle and the mucosal cells of the cobalt-perfused intestine showed no histological abnormalities. Immunohistochemical staining of tissues treated with 0.75-1.5 g/dl cobalt solutions revealed absence of substance P, Met-enkephalin, and VIP immunoreactivity in all section studied; control segments showed the presence of all three peptides. Cobalt chloride in concentrations of 0.75-1.5 g/dl causes degeneration of intestinal intramural nerves and provides an experimental model suitable for studying the role of these nerves in small intestinal function.

Alteration of endothelium-dependent distribution of myocardial blood flow after coronary occlusion and reperfusion.

We have previously demonstrated that intracoronary infusion of the endothelium-dependent vasodilators acetylcholine, ATP, or arachidonic acid produces a preferential increase in subendocardial blood flow in anesthetized dogs. This study was performed to assess the effects of coronary artery occlusion and reperfusion on the distribution of myocardial blood flow produced by endothelium-dependent and endothelium-independent vasodilators. The endothelium was damaged by occlusion of the left anterior descending coronary artery for 45 minutes followed by 60 minutes of reperfusion in pentobarbital-anesthetized dogs. Intracoronary infusions of the endothelium-dependent vasodilators acetylcholine, bradykinin and thiazolylethylamine or the endothelium-independent vasodilator sodium nitroprusside were performed, and regional myocardial blood flow (by radioactive microspheres) was measured before and after occlusion and reperfusion. There were no changes in systemic hemodynamics during intracoronary infusion of vasodilators before or after coronary occlusion and reperfusion. All vasodilators produced similar increases in transmural blood flow before occlusion; however, only the endothelium-dependent vasodilators produced a significant increase in the subendocardial-to-subepicardial blood flow ratio. Increases in transmural flow as well as the preferential increase in subendocardial blood flow produced by acetylcholine, bradykinin, and thiazolylethylamine were attenuated after coronary occlusion and reperfusion. In contrast, increases in transmural blood flow produced by sodium nitroprusside were unchanged. These results suggest that the preferential increase in subendocardial perfusion produced by acetylcholine, bradykinin, and thiazolylethylamine is endothelium-dependent and may be selectively modified by ischemic insult.

Antigenic and catalytic disparity in the distribution of cytochrome P-450-dependent 25-hydroxyvitamin D3-1 alpha- and 24-hydroxylases.

Chick 25-hydroxyvitamin D3-1 alpha-hydroxylase, a cytochrome P-450 monooxygenase with a molecular weight of 57 kDa, can be isolated as described by Mandel et al. (1990 b). Under normal physiological circumstances, it occurs exclusively in kidney mitochondria. An isozyme of the 1 alpha-hydroxylase, known as the 24-hydroxylase, which uses the same substrate to yield an isomeric product, is also a cytochrome P-450 monooxygenase, has a molecular weight of 55 kDa, and like-wise occurs in kidney mitochondria. The amino-terminal sequences of the first 10 residues of the two isozymes are 100% homologous. Monoclonal antibodies of the IgM class raised against the 1 alpha-hydroxylase, which quantitatively discriminate against other P-450 cytochromes of mitochondrial or microsomal origin, recognize and interact with the 24-hydroxylase as an antigen. In the present study we show that the intestine, which is the only non-renal tissue with demonstrable 24-hydroxylase activity, gives a positive peroxidase-antiperoxidase immunohistochemical reaction using the monoclonal antibodies against the 1 alpha-hydroxylase. The reactions revealed that the antigen in the kidney is restricted to the cortical proximal tubular cells while in the intestine, the antigen is localized in the enterocytes of the villi. In kidney medullary or intestinal crypt cells, or in liver, heart and lung tissues where 1 alpha-hydroxylase or 24-hydroxylase activity could not be detected using cell or tissue homogenates, the immunohistochemical reactions were also negative.(ABSTRACT TRUNCATED AT 250 WORDS)

Monoclonal antibodies to chick renal calcium regulating hemeproteins. Biochemical and immunohistochemical interactions with mitochondrial 25-hydroxyvitamin D3 hydroxylases.

The kidney mitochondrial monooxygenases known as 25-hydroxyvitamin D3 1 alpha- and 24R-hydroxylases are two analogous enzymes which utilize the vitamin as a common substrate for the catalytic production of 1 alpha,25-dihydroxyvitamin D3 and 24R,25-dihydroxyvitamin D3. These two enzymes are complexes of NADPH-ferredoxin reductase, and an (Fe-S)-cluster containing ferredoxin with a redox potential that allows the ultimate transfer of reducing equivalents to the terminal oxidases distinctly known as cytochromes P-450(1) alpha and P-450(24). We have used in vitro immunizations of splenocytes obtained from mice sensitized with the purified cytochrome P-450(1) alpha to generate three hybridoma clones from fusion with p3 x 63.Ag8.653 myeloma ATCC cells which selectively secrete monoclonal antibodies (MAbs) of the IgM class. The MAbs have been partially purified by ammonium sulfate fractionation followed by size separation chromatography on Sephacryl S-200-HR. We have compared the structural similarities and differences between the two kidney enzymes in Western Blot analyses using horseradish peroxidase conjugated goat anti-mouse Igs specific for the heavy and light chains of mouse IgA, IgG and IgM. The MAbs from all three clones recognized and interacted with apparent common epitopes of the two hydroxylases but selectively discriminated against liver microsomal P-450LM2 type and adrenal mitochondrial P-450SCC cytochromes. The cytochromes P-450(1) alpha and P-450(24) were detected as two separate bands with approximate molecular weights of 57 and 55 KDa, respectively. In reconstitution of hydroxylase activities in vitro, the MAbs were equally effective in inhibiting the 1 alpha-hydroxylation and 24R-hydroxylation reactions. The ratio of micrograms of Igs to pmol cytochrome P-450 for a 50% inhibition of either activity was approximately 25. These results, collectively, seem to suggest the existence of a precursor-product relationship between the kidney mitochondrial 1 alpha- and the 24R-hydroxylases, or perhaps, a common ancestral origin. Immunochemical peroxidase anti-peroxidase staining of kidney tissue first exposed to the MAbs revealed that only the proximal tubular segment of the nephron was specifically enriched with the cytochromes.

Effects of complement depletion on glomerular eicosanoid production and renal hemodynamics in rat nephrotoxic serum nephritis.

The role of complement in mediating the changes in renal hemodynamics and glomerular eicosanoid synthesis after the administration of heterologous antibody against rat glomerular basement membrane (AGBM) was studied in Munich-Wistar rats. AGBM serum decreased glomerular filtration rate (GFR) and increased glomerular thomboxane B2 (TxB2) production without associated changes in glomerular prostaglandin E2 (PGE2) or PGF2 alpha production. Pretreatment of rats with cobra venom factor to deplete complement blocked the fall in GFR produced by AGBM without altering the increment in glomerular TxB2 production. In these animals, glomerular PGE2 synthesis was elevated. The results indicate that the salutary effects of complement depletion in nephrotoxic serum nephritis are not mediated by changes in the glomerular production of the vasoconstrictor TxA2. An enhanced production of PGE2 may participate in preventing the fall in GFR after AGBM administration in the complement-depleted rats.

Clinical heterogeneity and treatment response in inclusion body myositis.

Inclusion body myositis has been described as an inflammatory myopathy with distinctive clinical and pathologic features that is refractory to treatment. Ten cases of inclusion body myositis, as defined by histopathologic findings, were reviewed to determine whether the clinical characteristics are different in patients whose disease has been defined by light and electron microscopic studies compared with those whose disease has been defined by light microscopic studies alone. The clinical characteristics of both groups of patients were similar, and 2 patients have had excellent responses to treatment. Although inclusion body myositis represents a histologic subset of polymyositis, from a clinical perspective, it must be considered a nonspecific designation. Despite a generally poor prognosis, therapeutic intervention is still warranted.

Acquired progressive kinking of the hair.

A 14-year-old girl had acquired progressive kinking of the hair. Light microscopy disclosed flattening of the hair shafts with partial twists at irregular intervals. Cross-sections of paraffin-embedded hairs were elliptic or irregular in configuration. Scanning electron microscopy confirmed the presence of partial twists and demonstrated canalicular grooves that extended for variable lengths along the hair shafts. Acquired progressive kinking of the hair most resembles woolly hair in appearance and structural abnormalities.

Pathogenesis of acute pulmonary inflammation in strain 2 and strain 13 guinea pigs.

An acute inflammatory response was elicited in the lungs of strain 2 and 13 guinea pigs following immunization and aerosol challenge with ovalbumin. The pulmonary inflammatory response, characterized by hemorrhage and influx of inflammatory cells, progressed from initiation at 12-hours postchallenge through resolution at 96-hours postchallenge. Inflammatory and immunoregulatory cells, recovered by bronchoalveolar lavage, showed quantitative changes in their relative contribution to the bronchoalveolar cell infiltrate over the course of inflammation. Changes in concentrations of macrophages and T cells, in particular, are discussed in terms of their possible contributions to initiation and resolution of acute pulmonary inflammation.

Cellular immunoregulation of acute pulmonary inflammation in strain 2 guinea pigs.

Subclasses of lung immunoregulatory T cells were analyzed during acute pulmonary inflammation in strain 2 guinea pigs and compared with T cell subpopulations in the peripheral circulation. Immunized animals were aerosol-challenged with specific antigen and sacrificed at 12-, 24-, 48-, 72-, and 96-hours postchallenge. Mononuclear cells, isolated from peripheral blood and bronchoalveolar lavage, were enriched for T cells. The percentage of helper T cells, as well as antigen-specific blastogenesis, in recovered pulmonary T cells exhibited maximal values at 12-, 24-, and 96-hours postchallenge. In contrast, the presence of suppressor T cells correlated with decreased blastogenesis and antigen-specific suppression in isolated lung cells at 72-hours postchallenge. Since changes in pulmonary cells did not correlate with those found in the peripheral circulation, immunoregulatory events in these two compartments may be distinct. These results indicate that the proportions of lung T cell subclasses, as well as their in vitro functional activity, are altered over the course of pulmonary disease. Such changes in immunoregulatory cell populations may be important in the mediation of disease pathogenesis.

Regulation of pH in rat papillary tubule cells in primary culture.

To investigate the mechanisms responsible for urinary acidification in the terminal nephron, primary cultures of cells isolated from the renal papilla were grown as monolayers in a defined medium. Morphologically, cultured cells were epithelial in type, and similar to collecting duct principal cells. Cell pH measured fluorometrically in monolayers grown on glass slides showed recovery from acid loads in Na+-free media. Recovery was inhibited by cyanide, oligomycin A, and N-ethylmaleimide. Cyanide and oligomycin inhibited recovery less in the presence than in the absence of glucose. When cells were first acid loaded in a Na+-free medium and then exposed to external Na+, pH recovery also took place. This recovery exhibited first-order dependence on Na+ concentration and was inhibited by 5-(N-ethyl-N-isopropyl)amiloride. These studies demonstrate that in culture, collecting duct principal cells possess at least two mechanisms for acid extrusion: a proton ATP-ase and an Na+-H+ exchanger. The former may be responsible for some component of the urinary acidification observed in the papillary collecting duct in vivo; the role of the latter in acid-base transport remains uncertain.

Evidence that stimulation of 1,25(OH)2D3 production in primary cultures of mouse kidney cells by cyclic AMP requires new protein synthesis.

When primary culture of C75BL6 mouse cortical kidney cells in serum-free medium were incubated with unlabeled 25(OH)D3, they produced a metabolite which co-migrated with authentic 1,25(OH)2D3 and which could be measured by competitive receptor assay. A metabolite co-migrating with authentic 10-oxo-19-nor-25-OH-D3 was also produced. However, when cultures were incubated with 25(OH)D3 for 1 hour or longer, 10-oxo-19-nor-25-OH-D accounted for less than 15% of the total 3H-1,25(OH)2D3 displacement activity. Production of 1,25(OH)2D3 increased with increasing content of the culture, with time of incubation, and with substrate concentration. The apparent Km was 1.4 +/- 0.6 microM and Vmax 2.6 +/- 0.4 pM/mg protein/hr. These cultures possessed a very high level of phosphodiesterase activity, as indicated by their high cyclic AMP (cAMP) response to IBMX. This high phosphodiesterase activity may have been responsible for the lack of stimulation of 1,25(OH)2D3 production by physiologic or near physiologic concentrations of parathyroid hormone (PTH) in the absence of IBMX. However, when IBMX 10(-6) M was present, bPTH 10(-9) M significantly increased production of both cAMP and 1,25(OH)2D3. There was a close correlation between 1,25(OH)2D3 production and cAMP content of the cultures (basal or stimulated). An incubation time of at least 4 hours was required for cAMP to increase 1,25(OH)2D3 production and was inhibited in the presence of cycloheximide and actinomycin D. This study further documents the regulation of renal 1,25(OH)2D3 synthesis by PTH in mammalian kidney and provides evidence for cAMP as a possibly important second messenger in this effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Calcium oxalate crystal interaction with rat renal inner papillary collecting tubule cells.

Rat renal inner papillary collecting tubule cells (RPCT) have been isolated and maintained in primary culture. The cells have been found to be of only one type and they have maintained the characteristics of RPCT cells. The RPCT cells in culture appear as a monolayer with intermittent clumps of rounded cells. When small calcium oxalate monohydrate crystals (COM) or calcium oxalate dihydrate crystals (COD) are added to the monolayer of RPCT cells, the crystals bind on or about these clumps of rounded-up cells. The use of this system as a model for the study of crystal membrane interactions in crystalluria and urolithiasis is discussed.

BSS Plus: a potential irrigating solution for neurosurgery.

BSS Plus is a pH-stable balanced salt solution similar to glutathione bicarbonate Ringer's solution. Extensively used in ophthalmology, it is of potential value in neurosurgery. In comparative tests of its effectiveness, 28 cats underwent bilateral irrigation of the surface of the cerebral cortex with normal saline on one side and BSS Plus on the other. After 2 hours, a marked decrease was seen in the surface pH of the hemisphere irrigated with normal saline but not of the hemisphere treated with BSS Plus. Blood-brain barrier changes (measured with Evans blue dye techniques) were more evident following saline irrigation. Somatosensory evoked potentials and cerebral blood flow were not significantly altered. Conventional light microscopy using three standard stains did not reveal a significant difference. Transmission electron microscopy studies were performed in 14 animals and scanning electron microscopy in six. In five animals both transmission and scanning electron microscopy studies were conducted after irrigation with both agents without a cottonoid cover and with immediate harvest of superficial layers from the living brain and immersion-fixation in glutaraldehyde. Tissue preservation was superior on the BSS Plus side in all studies. This agent may represent an improved irrigation solution for neurosurgery, but further studies are required.

Specificity and duration of post-inflammatory suppression in rabbit lungs challenged with aerosolized antigen.

Rabbits immunized and aerosolized with soluble protein antigens develop a short lived pulmonary inflammation. This is followed by a period of non-specific unresponsiveness which lasts approximately 30 weeks after the first exposure to aerosol treatment. This period is characterized by the inability of the rabbit to exhibit another inflammatory reaction either to the same antigen used to induce the first inflammation, or to a new antigenically unrelated antigen. After 30 weeks however, the animals become responsive (develop another pulmonary inflammation) to a second unrelated antigen, but remain unresponsive to the antigen used to elicit the initial inflammatory response. These studies indicate that following challenge with inhaled antigen, rabbits develop a non-specific suppression of pulmonary inflammation which lasts a finite period of time. When this disappears, the animal is left with an antigen specific suppression of pulmonary inflammation. These studies suggest a model for normal individuals who may respond similarly to potentially harmful inhaled allergens. Individuals with hypersensitivity pneumonitis, however, may not develop antigen specific unresponsiveness. The nature of this unresponsiveness is unknown at present, nor is it known when it begins to develop.

Successful second kidney transplantation in a patient with focal glomerulosclerosis. A case report.

We report a woman who developed renal failure due to focal glomerulosclerosis (FGS). This disease recurred immediately in a kidney transplant from her brother resulting in removal of that graft. She subsequently received a cadaver kidney transplant, and FGS has not recurred after 24 months. This is the first report of nonrecurrence in a second kidney graft, when the first was lost due to recurrent FGS. Whether timing or tissue typing of the second graft in relationship to the first is important is not known. Recurrence of FGS in a first kidney graft should not, however, preclude future transplantation.

Pathogenesis of postmyelographic arachnoiditis.

The causal relationship between a myelogram with an aqueous contrast medium and postmyelographic arachnoiditis has not been clarified. Primates after myelography with metrizamide or meglumine iocarmate were studied with fluorescent microscopy, energy dispersion analysis and with scanning and transmission electron and light microscopy. All controls and, up to the eighth day after myelography, all treated animals had normal-appearing arachnoid membranes by microscopy. After eight days the treated animals had progressively more severe arachnoid fibrosis. Energy dispersive analysis revealed iodine in the arachnoid only up to 24 hours after myelography. Fluorescent microscopy revealed no evidence of immune complexes in the arachnoid. The chronic effects of water-soluble media on the arachnoid are not apparently mediated by contrast medium persisting in the arachnoid or by immune complexes.