Electron microscopy in AIDS-related infectious diseases. I. Acanthamoebiasis.
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AIDS-Related Opportunistic Infections↗
Biomedical subjects
K Hashimoto
Publications and source records attributed to K Hashimoto.
Accordion-like structure of terminal hair follicles of the human scalp.
Terminal hair follicles extracted after ethylenediaminetetraacetic acid treatment preserved the basal cell surface of the outer root sheath well enough to examine the outer surface in detail. Light microscopic observations of whole mount specimens revealed several sawtooth-like structures of follicular epithelium in the lower portion of terminal hair follicle. Vertical sections of the human scalp also showed several invaginations of the outer root sheath of terminal hair follicles in the lower portion, not in association with the arrector pili muscle. Scanning electron microscopy of the same specimens demonstrated accordion-like structures below the sebaceous gland in the lower half of anagen terminal hair follicles and surrounding the entire circumference of the follicles. Sawtooth-like structures were unilaterally observed at the level of the middle or lower portion below the sebaceous gland. With transmission electron microscopy, these structures were seen as undulations of basal cells which preserved hemidesmosomes, although the basal lamina had been peeled off during the extraction procedure. Thus, this accordion-like structure is a genuine structural variation of some human anagen hair follicles and not an artifact.
Basement Membrane↗
Evaluation of antiherpetic compounds using a gastric cancer cell line: pronounced activity of BVDU against herpes simplex virus replication.
We developed a rapid and simple method for the screening of antiviral agents against herpes simplex virus (HSV) in a model of gastrointestinal herpetic infection in vitro. This method was based on inhibition of HSV-induced cytopathogenicity in gastric adenocarcinoma MKN-28 cells, as monitored by an MTT colorimetric assay. From the various compounds that were evaluated for their activity against HSV-1 and HSV-2, brivudine (BVDU) emerged as the most effective. When the 50% effective concentration (EC50) values of the antiherpes agents in MKN-28 cells were compared with those in human embryo lung MRC-5 cells, all compounds, except for BVDU, showed higher EC50 values in MKN-28 cells. For BVDU the EC50 values in MKN-28 cells were 0.8 (HSV-1) and 0.036 (HSV-2) times the EC50 values in MRC-5 cells. Thus BVDU was 27.5 times more active against HSV-2 in MKN-28 cells than in MRC-5 cells. The MKN-28 gastric cancer cells may be useful for the rapid screening of anti-HSV agents and, in particular, those that may be useful in therapy of gastrointestinal HSV infections in gastrointestinal herpetic infection.
Adenocarcinoma↗
Serum theophylline concentration levels and preventative effects on exercise-induced asthma.
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Adolescent↗
Coexistence of gene mutations causing Fabry disease and Duchenne muscular dystrophy in a Japanese boy.
Both Fabry disease and Duchenne muscular dystrophy were confirmed by gene analysis in a Japanese boy. He developed muscle weakness at 4 years of age. A muscle biopsy revealed lamellar inclusion bodies in vascular endothelial cells in addition to myopathic changes with negative dystrophin staining. The myopathic symptoms progressed, and he died of pneumonia at 24 years of age. No clinical manifestations of Fabry disease were observed except for hypohidrosis and angiokeratoma. However, glycolipid accumulation was found in biopsied renal tissue. Molecular analysis demonstrated two gene mutations; a novel single-base deletion in exon 3 of the alpha-galactosidase gene, and a dystrophin gene deletion extending from exon 46 to exon 50. His mother was confirmed to be heterozygous for both gene deletions.
Adult↗
Cortical dysgenesis in a patient with Turner mosaicism.
In a patient with Turner mosaicism who had mental retardation, epilepsy and cerebellar ataxia, MRI showed cerebellar atrophy and a bizarre cortical dysgenesis of the cerebrum, which was considered to comprise a mixture of relatively normal gyri and structures resembling pachygyria and lissencephaly. The karyotype of the patient was 45,X/47,XXX, but the brain dysgenesis could not be explained solely on the basis of this mosaicism, which is rarely associated with a gross abnormality in brain pathology. Abnormality of the X chromosome seems to have some potential for inducing cortical dysgenesis, and this case may be partially attributable to an abnormal locus on the X chromosome.
Adult↗
IK independent class III actions of MS-551 compared with sematilide and dofetilide during reperfusion in anaesthetized rats.
1. The antiarrhythmic and haemodynamic effects of three class III antiarrhythmic drugs, MS-551, sematilide and dofetilide, were examined in the coronary artery, ligation-reperfusion model of pentobarbitone-anaesthetized rats, a species deficient in functional cardiac IK. MS-551 is a non-selective potassium channel blocker, while both sematilide and dofetilide are selective delayed rectifier potassium (K) channel (IK) blockers. 2. Before coronary ligation, 3 and 10 mg kg-1 MS-551 decreased the heart rate by 6% (P < 0.01) and 12% (P < 0.01), and increased mean arterial pressure (MAP) by 14% (P < 0.05) and 33% (P < 0.01), respectively. Sematilide at 10 and 30 mg kg-1 also decreased the heart rate by 4% (P < 0.01) and 9% (P < 0.01), respectively, and the higher dose of 30 mg kg-1 decreased MAP by 29% (P < 0.01). Dofetilide, 1 mg kg-1, decreased the heart rate (P < 0.01), but had no significant effect on MAP. 3. The QT interval was increased by 10% (P < 0.01) and 31% (P < 0.01), when 3 and 10 mg kg-1 MS-551 were given. Sematilide and dofetilide had no effect on the QT interval. 4. Immediately after reperfusion, lethal ventricular fibrillation (VF) was induced in 80% of the saline group. MS-551 at 3 and 10 mg kg-1, reduced the incidence of lethal VF to 50% and 20% (P < 0.05). Neither dofetilide 1 mg kg-1 nor sematilide (10 and 30 mg kg-1) decreased the incidence of lethal VF (70%, 80% and 50%, respectively). None of the three drugs had any effect on the occurrence of reperfusion-induced VT or the total incidence of VF. However, 10 mg kg-1 MS-551 delayed the onset of reperfusion-induced VF (27 +/- 5 s compared with 12 +/- 2 s of the control group, P < 0.05). 5. In conclusion, in rats which are deficient in cardiac IK MS-551 prolonged the QT interval and reduced the incidence of sustained VF after reperfusion. Blockade of channels other than IK might participate in the defibrillatory effect of MS-551. Sematilide and dofetilide, which are selective IK blockers, did not increase the QT interval nor did they show antiarrhythmic effects Mechanisms other than K channel block may be involved in the different effects of the three drugs on blood pressure.
Animals↗
Clinical features and natural history of spinocerebellar ataxia type 1.
SCA1 is a dominant spinocerebellar ataxia (SCA) and a multi-systemic syndrome caused by abnormal expansion of unstable CAG repeat in a novel gene located on chromosome 6p22-p23. We clinically studied 35 Japanese SCA1 patients who were assumed to have come from a common origin. The age at onset ranged from 15-63 years, and significantly correlated with CAG repeat units of mutant alleles. Ataxia was the initial symptom, and the majority of patients had a similar history of signs and symptoms. Nystagmus was at first minimal, later attenuated, and a slow saccade followed. Limb tendon reflexes were mostly hyperactive and depressed with the development of diffuse amyotrophy. The cardinal feature was ataxia-hyperreflexia-late slow saccade syndrome with terminal amyotrophy. Although the phenotype of SCA1 overlaps with those of other dominant SCAs, some facets of the neurological events differ from either SCA2 with ataxia-hyporeflexia-slow saccade syndrome, or early-onset Machado-Joseph disease with dystonia-bradykinesia-spasticity syndrome.
Adolescent↗
Sudoriferous acrosyringeal acantholytic disease. A subset of Grover's disease.
Three selected cases of transient acantholytic dermatosis were studied because of their definitive correlation with sweating due to fever and/ or bed-ridden situations. Biopsy specimens were serially sectioned and acantholysis was found in the acrosyringium or traced to connect to the acrosyringium in all biopsy specimens. Carcinoembryonic antigen (CEA) and eccrine gland-specific monoclonal antibody, IKH-4, were positive in acantholytic cells. Electron microscopy revealed electron dense material filling the lumen of intraepidermal eccrine ducts. This material leaked into lateral intercellular spaces of the luminal cells, passing tight junctions. Marked edema and numerous lysosomes were reminiscent of those found when eccrine acrosyringium is formed in the embryo; this suggested that an occluded and damaged eccrine intraepidermal duct was being rebuilt via lysosomal digestion.
Acantholysis↗
Curvicircular intracytoplasmic membranous structures in keratinocytes of pemphigus foliaceus.
We noticed intracytoplasmic membranous, annular, or circular structures in the lesion of pemphigus foliaceus and studied these by regular transmission electron microscopy and immunoelectron microscopy. These curvicircular bodies were observed in the preacantholytic keratinocytes of the blister wall as well as in acantholytic cells in 6 out of 6 patients with pemphigus foliaceus. They were absent in samples from 3 patients with pemphigus vulgaris. These structures were about 60-70 nm wide and consisted of 4 electron-dense layers. They were continuous with intact desmosomal structures and gap junctions in the periphery of the keratinocytes. These curvicircular membranous bodies were well labeled with immunogold particles for desmoglein, plakoglobin, connexin 43, and IgG. In contrast to pemphigus vulgaris, splitting of desmosomes through dissolution of intercellular desmoglea was seldom observed in all 6 specimens of pemphigus foliaceus. These findings suggest that in pemphigus foliaceus 1) curvicircular bodies are derived from internalized desmosomes and gap junctions, and 2) cell-to-cell adhesions are weakened by this internalization and acantholysis is initiated, while in pemphigus vulgaris the dissolution of desmoglea is the initial event. It is suggested that in pemphigus foliaceus the binding of autoantibody induces internalization of many intact desmosomes and gap junctions rather than splitting them.
Fluorescent Antibody Technique↗
Specific detection of anti-cell surface antibodies in herpes gestationis sera.
We examined 42 herpes gestationis sera with immunofluorescence of normal human skin sections, and found that anti-keratinocyte cell surface antibodies were detected specifically in 10 herpes gestationis sera. The diagnosis of these herpes gestationis cases was confirmed by detecting antibodies against the 180 kD bullous pemphigoid antigen with immunoblotting of its fusion protein. The results of immunoadsorption assay using baculoproteins of both pemphigus vulgaris and pemphigus foliaceus antigens indicated that the herpes gestationis sera did not recognize common pemphigus antigens. Immunoblotting of human epidermal extracts and immunofluorescence of various tissues also suggested that the sera did not recognize any other desmosomal components or paraneoplastic pemphigus antigens. The significance of this reactivity is unclear. However, because no control bullous pemphigoid sera showed this reactivity, it may suggest a different pathophysiology between herpes gestationis and bullous pemphigoid.
Antigens, Surface↗
Elevated nitric oxide concentration in the seminal plasma of infertile males: nitric oxide inhibits sperm motility.
PROBLEM: To evaluate the effect of nitric oxide in the seminal plasma on sperm motility. METHOD: Seminal plasma concentrations of NO2-, a stable end product of nitric oxide, of 108 males of infertile couples and 15 proven fertile donors were measured and compared with spermatogram parameters. Motile sperm was incubated with a nitric oxide-generating drug, sodium nitroprusside, for 6 hr in the absence or presence of oxyhemoglobin, an inhibitor of nitric oxide. RESULTS: The NO2- concentration in the seminal plasma was 6.58 +/- 0.5.6 microM in 26 infertile males with leukocytospermia, 5.51 +/- 0.25 microM in 82 infertile males without leukocytospermia, and 3.91 +/- 0.16 microM in 15 controls. There was a significant correlation between the NO2- concentration and sperm motility. Sodium nitroprusside reduced the sperm motility in a dose- and time-dependent manner and its reduction was completely inhibited by the addition of oxyhemoglobin. CONCLUSION: These findings indicate that nitric oxide concentration in the seminal plasma of infertile males is elevated and that nitric oxide is an inhibitor of sperm motion.
Cell Survival↗
Phospholipid metabolism induced by Clostridium perfringens alpha-toxin elicits a hot-cold type of hemolysis in rabbit erythrocytes.
GTP and AIF4- significantly stimulated the late phosphatidic acid (PA) formation induced by Clostridium perfringens alpha-toxin in rabbit erythrocyte lysates. Pertussis toxin blocked the PA production. AIF4- markedly enhanced phosphatidylethanol production induced by alpha-toxin in the presence of ethanol. GTP[gamma S] stimulated the PA formation and hemolysis induced by alpha-toxin, and GDP[beta S] inhibited them. An H-to-G mutation at position 126 (H126G) induced the PA formation and hemolysis in a Co2+ concentration-dependent manner. H148G induced neither the PA formation nor hemolysis. These results suggest that the toxin-induced hemolysis is due to activation of phospholipid metabolism systems through GTP-binding protein.
Aluminum Compounds↗
Serum and synovial fluid levels of interleukin-5 in a patient with eosinophilic fasciitis.
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Adult↗
Maintenance of imprinting of the insulin-like growth factor II gene (IGF2) and the small nuclear ribonucleoprotein polypeptide N gene (SNRPN) in the human uterus and leiomyoma.
The insulin-like growth factor II gene (IGF2) is thought to be involved in the growth of uterine smooth muscle tumors. We studied the allele-specific expression of IGF2 in 20 patients with uterine leiomyomas by analyzing restriction fragment length polymorphisms (RFLP), because IGF2 is a maternally imprinted gene and only the paternal allele is exclusively expressed in human somatic tissue. We also studied the allelic expression of the small nuclear ribonucleoprotein polypeptide N gene (SNRPN), which is reportedly maternally imprinted in humans, and compared the imprinting status with that of IGF2. Nine patients (45%) were heterozygous at the ApaI site of IGF2, nine (45%) were heterozygous at the possible AccII polymorphic site of SNRPN, and three (15%) showed polymorphism in both genes. The genomic DNA of 15 patients showed heterozygosity in either or both of these genes, and the mRNA of these was expressed monoallelically in myometrial tissues and leiomyomas of these patients. These results demonstrated that IGF2 and SNRPN imprinting is completely maintained in human uteri and leiomyomas and that increased expression of IGF2 is not due to biallelic expression.
Autoantigens↗
Plasma nitric oxide levels in pregnant patients with preeclampsia and essential hypertension.
Nitric oxide (NO) production may be an important causal factor in hypertensive disorders during pregnancy. The plasma concentrations of NO2-(+) NO3-, stable metabolites of NO, were measured in 70 nonpregnant women, 323 normotensive pregnant women, 23 pregnant patients with preeclampsia, and 7 pregnant patients with essential hypertension. The normotensive women had higher plasma concentrations (30.0 +/- 0.6 mumol/l) than nonpregnant women (18.3 +/- 1.0 mumol/l; p < 0.0001). The plasma concentrations in the patients with preeclampsia (45.6 +/- 2.3 mumol/l) were higher than in the normotensive women (30.3 +/- 1.0 mumol/l; p < 0.0001) and were correlated with the systolic blood pressure (r = 0.442; p < 0.05). However, pregnant patients with underlying essential hypertension had significantly lower plasma concentrations (19.1 +/- 3.0 mumol/l; p < 0.005). These findings suggest that NO contributes to maternal vasodilation, the maintenance of uterine quiescence, and the pathogenesis and clinical features of hypertensive disorders during pregnancy.
Adult↗
PPBP [4-phenyl-1-(4-phenylbutyl) piperidine] decreases brain injury after transient focal ischemia in rats.
BACKGROUND AND PURPOSE: We tested the hypothesis that intravenous administration of the potent sigma-receptor ligand 4-phenyl-1-(4-phenylbutyl) piperidine (PPBP) during transient focal ischemia would decrease postischemic brain infarction volume in rats. METHODS: Rats underwent intravascular focal ischemia for 2 hours followed by 22 hours of reperfusion. Halothane anesthesia was used only during initiation and cessation of ischemia. Rats received saline (n = 10) or 1 mumol/kg per hour PPBP (n = 10) by continuous intravenous infusion starting 1 hour after the initiation of ischemia and continuing through 22 hours of reperfusion. RESULTS: There was no difference between groups in blood pressure, arterial blood gas values, and body temperature. Triphenyltetrazolium-determined infarction volume of ipsilateral cerebral cortex (saline, 39 +/- 6%; PPBP, 21 +/- 7% of ipsilateral hemisphere; mean +/- SEM) and striatum (saline, 68 +/- 6%; PPBP, 33 +/- 8% of ipsilateral striatum) was smaller in rats treated with PPBP than in rats treated with saline. CONCLUSIONS: These data indicate that sigma-receptors may play an important role in the mechanism of injury both in cortex and striatum after 2 hours of transient focal ischemia in rats. Because PPBP afforded protection when administered at the end of ischemia and during reperfusion, sigma-receptors may influence the progression of injury in ischemic border regions.
Animals↗
MR imaging of spastic diplegia. The importance of corpus callosum.
PURPOSE: The MR findings in patients with spastic diplegia were investigated and the role of MR imaging in assessing the extent of brain injury was evaluated. MATERIAL AND METHODS: 39 male and 24 female patients (preterm/term 43/20) were imaged using a 0.5 T MR system. RESULTS: The MR findings in term patients were quite different from those in preterm patients; 55% of the term patients showed normal and minimal changes on MR, whereas 90.7% of the 43 preterm children had periventricular leucomalacia. The deep cerebral white matter was the most frequently involved site. Objective measurements revealed significant reductions of the entire sagittal area of corpus callosum in diplegic patients in comparison with normal controls. The motor palsy severity correlated well with the extent of corpus callosum involvement. CONCLUSION: The corpus callosum appears to be a sensitive marker site for the assessment of the extent of white matter injury.
Case-Control Studies↗