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Biomedical subjects

M Rapoport

Publications and source records attributed to M Rapoport.

At least 19 recordsLinked to original sources

Right-left correlation of the sympathetically induced fluctuations of photoplethysmographic signal in diabetic and non-diabetic subjects.

Photoplethysmography (PPG) records the cardiac-induced changes in tissue blood volume by light-transmission measurements. The baseline and amplitude of the PPG signal show very low-frequency (VLF) spontaneous fluctuations, which are mediated by the sympathetic nervous system, and high correlation between right and left extremities of healthy subjects. As sympathetic neuropathy is one of the diabetic complications, the right-left correlation of the PPG fluctuations was examined in diabetic patients. The PPG signal was simultaneously measured in the two index fingers and the two second toes of 35 diabetic patients and 33 non-diabetic subjects. For each PPG pulse, the baseline and amplitude were determined, and the right-left correlation coefficients of the VLF fluctuations in the baseline and amplitude were derived. The VLF fluctuations in the baseline showed high right-left correlation, both for fingers (0.93 +/- 0.05) and toes (0.93 +/- 0.06), for the non-diabetic subjects, and significantly lower correlation (0.78 +/- 0.22 and 0.84 +/- 0.17, respectively) for the diabetic patients. Similar results were obtained for the amplitude VLF fluctuations. The right-left correlation coefficients for diabetic patients decreased with the disease duration for the toe baseline and toe amplitude fluctuations and correlated with heart rate response to deep breathing for the finger baseline and toe amplitude fluctuations. The right-left correlation coefficients of the PPG fluctuations provide a simple and convenient means for assessing the adequacy of the sympathetic nervous system function.

Adult↗

The synapsins: beyond the regulation of neurotransmitter release.

The synapsins are a family of five closely related neuron-specific phosphoproteins associated with the membranes of synaptic vesicles. The synapsins have been implicated in the regulation of neurotransmitter release. They tether synaptic vesicles to actin filaments in a phosphorylation-dependent manner, controlling the number of vesicles available for release at the nerve terminus. A growing body of evidence suggests that the synapsins play a broad role during neuronal development. They participate in the formation and maintenance of synaptic contacts among central neurons. In addition, each synapsin has a specific role during the elongation of undifferentiated processes and their posterior differentiation into axons and dendrites. In this review, we focus on these novel roles of synapsins during the early stages of development.

Animals↗

Zn metabolism affects apoptosis rate and proliferative responsiveness of PBMC from patients on chronic hemodialysis.

Patients with end-stage renal failure suffer from severe plasma trace metal deficiency that is not corrected by dialysis. Trace metals, including Zn(2+), are critical for cell differentiation and replication. Zn(2+)also plays important role in cell apoptosis. Both processes are known to be impaired in uremia. The present study was undertaken to evaluate the effect of Zn(2+) supplementation on apoptosis of cultured peripheral blood mononuclear cells (PBMC) from patients on chronic hemodialysis versus those from healthy control subjects, concomitantly with assessment of mitogen-induced cell proliferation. The results showed that (1) basal total cell-associated Zn(2+) was elevated in uremic PBMC, compared to normal controls (23.9 +/- 5.64 v 10.5 +/- 2.64 micromol/L/mg protein). The gap persisted following incubation in Zn(2+)-enriched medium (63.3 +/- 26.12 v 81.6 +/- 13.4 micromol/L/mg protein, P <.005). (2) Basal proliferative response to phytohemagglutinin (PHA) was significantly decreased in uremic PBMC compared to normal controls (12,000 +/- 1,560 cpm v 16,600 +/- 1,460 cpm, P <.01). Incubation of uremic PBMC in Zn(2+)-enriched medium improved their proliferative response to PHA, yielding counts per minute significantly higher compared to their normal counterparts (37,000 +/- 7,500 cpm v 22,000 +/- 3,000 cpm, P <.001). (3) Basal apoptosis rate in uremic PBMC was significantly elevated compared to normal control cells (7.6% v 2.6%, P <.05). Following incubation in Zn(2+)-enriched medium, apoptosis was increased both in normal and uremic PBMC. Percent apoptosis of uremic PBMC remained significantly elevated compared to control cells (11.7% v 5.7%). We conclude that uremic PBMC are more responsive to exogenous Zn(2+) in culture than their normal counterparts. This, among other abnormalities, might reflect an abnormal regulation of Zn(2+) transport by uremic mononuclear cell membranes. The resultant increase in total cell-associated Zn(2+) content improves poor proliferative responsiveness of uremic PBMC. On the other hand, increased total cell-associated Zn(2+) stimulates enhanced apoptosis in uremic PBMC, which, probably by eliminating defective cells, contributes to the functional capability of the population as a whole. The net effect of the 2 processes is still augmentation of cell proliferation.

Apoptosis↗

Effect of estrogen replacement therapy on speed of sound at multiple skeletal sites.

OBJECTIVES: To evaluate the effect of estrogen replacement therapy (ERT) on postmenopausal bone loss by multi-site ultrasound measurement. METHODS: A cross-sectional comparison of postmenopausal women, ERT users and non-users. The two study groups were enrolled for the reference database collection for the Sunlight Omnisense (Omnisense) and were matched by years since menopause. Speed of sound (SOS) was measured at the distal radius (RAD), mid-shaft tibia (TIB), fifth metatarsus (MTR) and proximal phalanx (PLX). RESULTS: 143 ERT users for 5.2+/-3.6 years were compared with 139 ERT non-users (age: 57.0+/-5.3 and 57.5+/-5.5, respectively). Both groups were 7.1+/-5.0 years since menopause. SOS, expressed in T-score units, was higher at the RAD in ERT users as compared to ERT non-users (-0.55+/-1.30 and -1.36+/-1.60, respectively, P<0.0001), and at the TIB (-0.73+/-1.34 and -1.28+/-1.45, respectively, P=0. 003). Same trend was observed at the MTR and PLX, but not statistically significant because of fewer observations. In early post menopause period, the ERT-non users RAD data shows an annual SOS decrease of 0.17 versus annual increase of 0.12 T-score units (P=0.037). Similar effect is observed at the TIB, though not statistically significant (non-users decrease of 0.20 vs. users increase of 0.08 T-score units/year, P=0.086). CONCLUSIONS: SOS measurements by Omnisense at multiple skeletal sites support the ERT protective effect on bone.

Aged↗

Synapsin III: developmental expression, subcellular localization, and role in axon formation.

We have investigated the developmental expression and subcellular localization of synapsin III, the newest member of the synapsin family, in cultured mouse hippocampal neurons. Our results indicate that synapsin III is expressed early during development, with levels peaking 7 d after plating and declining thereafter. Synapsin III is highly concentrated in growth cones. Using specific antisense oligonucleotides, we have also examined the effect of depleting synapsin III on neurite elongation and synaptogenesis. When synapsin III was suppressed immediately after plating, hippocampal neurons extended minor processes but failed to differentiate one of them as the axon. The suppression of synapsin III after axonal elongation did not affect the time course of synapse formation. The results indicate that synapsin III has a developmental time course, a subcellular localization, and a developmental function very different from those of synapsin I and synapsin II.

Animals↗

Reference database for bone speed of sound measurement by a novel quantitative multi-site ultrasound device.

The nonuniform skeletal involvement in osteoporosis argues for multi-site evaluation. The Sunlight Omnisense (Sunlight Ultrasound Technologies, Israel) is a multi-site device that measures speed of sound (SOS) at the appendicular skeleton. We report the reference database for SOS at the radius (RAD), tibia (TIB), metatarsus (MTR) and phalanx (PLX). The database was obtained from 1521 healthy Israeli women (age 20-90 years) out of 2051 respondents. SOS was determined in 97.6% of the participants at the PLX, 96.4% at the TIB, 93.6% at the RAD and 85.1% at the MTR; it was not measurable in 0.5%. Short-term coefficient of variation was lowest at the RAD and always less than 1%. Maximal SOS was noted at 35-45 years of age in three of the sites (RAD 4169 m/s, MTR 3663 m/s, PLX 4047 m/s, respectively) but 10 years earlier at the TIB (3939 m/s). In the perimenopausal period (age 46-55 years), SOS was always lower in post- as compared with premenopausal women (p<0.05). Immediately following the menopause, SOS annually declined close to the short-term CV: 16, 34, 37 and 13 m/s at the RAD, PLX, MTR and TIB, respectively. The average age-stratified SOS values at various measurement sites were highly correlated at the population level (0.96-0.99), but less so at the individual level (0.40-0.57). Therefore, multi-site SOS measurements are better than single-site assessment. After 79 years of age, the average T-score at the RAD and PLX was <--2.5. This is similar to that of dual-energy X-ray absorptiometry (DXA)-determined spine bone mineral density (BMD) and somewhat lower than hip BMD. Equivalent T-score curves obtained by percentile adjustment of SOS at various sites to that of the RAD (at age group 60-69 years) reveal convergence and indicate that 52-68% of women older than 79 years are osteoporotic. In conclusion, multi-site peripheral SOS measurements reveal age-dependent bone changes with a high degree of measurement precision and indicate a prevalence of osteoporosis similar to that obtained by DXA.

Adult↗

PD98059 prevents neurite degeneration induced by fibrillar beta-amyloid in mature hippocampal neurons.

How senile plaques and neurofibrillary tangles are linked represents a major gap in our understanding of the pathophysiology of Alzheimer's disease (AD). We have previously shown that the addition of fibrillar beta-amyloid (Abeta) to mature hippocampal neurons results in progressive neuritic degeneration accompanied by the enhanced phosphorylation of adult tau isoforms. In the present study, we sought to obtain more direct evidence of the signal transduction pathway(s) activated by fibrillar Abeta leading to tau phosphorylation and the generation of dystrophic neurites. Our results indicated that fibrillar Abeta induced the progressive and sustained activation of the mitogen-activated protein kinase (MAPK) in mature hippocampal neurons. On the other hand, the specific inhibition of the MAPK signal transduction pathway by means of PD98059, a MAPK kinase (MEK) specific inhibitor, prevented the phosphorylation of tau (at Ser199/Ser202) induced by fibrillar Abeta. In addition, the inhibition of MAPK activation partially prevented neurite degeneration. Taken collectively, our results suggest that the sustained activation of the MAPK signal transduction pathway induced by fibrillar Abeta may lead to the abnormal phosphorylation of tau and the neuritic degeneration observed in AD.

Amyloid beta-Peptides↗

The role of the cerebellum in cognition and behavior: a selective review.

The cerebellum has traditionally been seen primarily to coordinate voluntary movement, but evidence is accumulating that it may play a role in cognition and behavior as well. This is a selective review of studies assessing potential cognitive deficits and personality changes associated with cerebellar disease. Preliminary studies of the role of the cerebellum in schizophrenia, dementia, and other psychiatric disorders are also discussed. Efforts to understand the neurological substrates of behavior should consider the role of the cerebellum.

Behavior↗

Neonatal pig islets induce a lower T-cell response than adult pig islets in IDDM patients.

BACKGROUND: Pancreatic pig islets may provide a substitute in the future for difficult to obtain human islets for transplantation in insulin-dependent diabetes millitus (IDDM) patients. However, the immune response to xenografts may significantly hamper this approach. Because neonatal tissue is believed to be less immunogenic, we examined whether the T-cell response to neonatal pig islets differs from the response to adult islets. METHODS: The T-cell proliferative response to different concentrations of sonicated neonatal and adult pig islets, as well as to insulin and mitogens, was tested in 21 recent onset IDDM patients and 21 healthy controls. We determined the presence of various circulating islet autoantibodies and their association with the T-cell response in IDDM patients. RESULTS: In the IDDM patients, sonicated adult pig islets (at 1 microg protein/ml) induced a significantly higher frequency (12 of 21 vs. 1 of 21, p<0.001) and magnitude (2.58+/-0.44 vs. 1.38+/-0.13, p<0.02) of positive T-cell responses than neonatal islets at the same concentration. Similar results were obtained with a 10-fold higher concentration of islet sonicate. There was no significant association between the individual T-cell responses and the presence of circulating autoantibodies in IDDM patients. CONCLUSION: These results indicate that neonatal pig islets induce a lower T-cell reactivity than adult islets, suggesting that the neonatal tissue may be immunologically more suitable for future islet xenotransplantation.

Adolescent↗

Photosensitivity associated with antipsychotics, antidepressants and anxiolytics.

Photosensitivity reactions evoked by systemic agents are the result of the effects of the agent combined with subsequent exposure to light. Photosensitivity induced by exogenous parenteral agents accounts for an increasing portion of the total undesirable effects caused by environmental chemicals. The exponential increase in the number of new drugs introduced each year may be one of the factors explaining the increased number of reports describing photosensitivity induced by exogenous agents. There are many reports of photosensitivity caused by antipsychotic and antidepressant agents. Although the majority of the research was focused on the photosensitising potential of chlorpromazine, other antipsychotics and antidepressants have been shown to cause cutaneous photosensitivity. An extensive drug history must be taken whenever a patient presents with a reaction limited to, or accentuated in, light-exposed areas. It should be remembered that these reactions may present with a wide morphological spectrum ranging from sunburn-like responses to eczematous, lichenoid and even bullous lesions, resembling porphyria cutanea tarda. In order to properly diagnose photosensitivity to systemic drugs it is important to prove photosensitivity by phototesting and to rule out other causes of systemic photosensitivity such as systemic lupus erythematosus and porphyria cutanea tarda.

Anti-Anxiety Agents↗

Unusual bleeding manifestations of amyloidosis in patients with multiple myeloma.

We describe two patients who developed severe haemorrhagic complications. One manifested massive vaginal bleeding and the second haemopericardium with cardiac tamponade. In both cases histopathological examination showed subendothelial deposits of amyloid. Since other local and systemic causes of the haemorrhagic complications were excluded the bleeding was most probably due to amyloid angiopathy. Therefore, amyloid angiopathy should be considered in the differential diagnosis of bleeding in patients with amyloidosis associated with multiple myeloma.

Aged↗

Autoimmune diabetes induced by the beta-cell toxin STZ. Immunity to the 60-kDa heat shock protein and to insulin.

Administered at a suitably low dose, the toxin streptozotocin (STZ) can trigger an autoimmune process leading to destruction of the beta-cells of the pancreatic islets. In this study, we examined specific immunological reactions in mice before and during the development of STZ-induced autoimmune diabetes. We now report that the development of spontaneous autoantibodies to insulin can serve as a marker of susceptibility to a low dose of STZ. Susceptible male mice of the C57BL/KsJ strain manifested such anti-insulin antibodies, and resistant female mice did not. Administration of a low dose of STZ (five daily doses each of 30 mg/kg) induced transient hyperglycemia approximately 20-30 days later, which temporarily remitted but was followed by intractable diabetes approximately 2.5 months later. The diabetogenic process triggered by the low dose of STZ was associated with an increase in the level of anti-insulin antibodies bearing the Dana and Micha (DM) idiotype, later followed by the appearance of anti-idiotypic antibodies that peaked before the onset of diabetes. Antibodies and T-cells reactive to hsp60 (heat shock protein) were triggered by the low-dose STZ administration and persisted throughout the period that preceded clinical diabetes. T-cells reactive to the p277 peptide of hsp60 were also observed. Finally, active immunization to hsp60 caused transient hyperglycemia by itself and also aggravated the hyperglycemia induced by low-dose STZ. Thus, autoantibodies to insulin can indicate susceptibility to a toxic trigger of diabetes, and a low dose of a toxin can activate the insulin and hsp60 autoimmunity that has been detected previously in the spontaneous autoimmune diabetes of NOD strain mice.

Animals↗

Recurrent acute renal failure complicating IgG warm-type autoimmune intravascular haemolysis.

A 44-year-old woman experienced recurrent episodes of massive intravascular haemolysis complicated by acute oliguric renal failure over a period of 22 years. The haemolysis was induced by IgG warm type autoantibody and complement and responded to corticosteroid therapy. The renal failure was treated effectively by dialysis. To our knowledge, such a life long occurrence of recurrent intravascular haemolysis induced by IgG warm type autoantibodies together with renal failure has not been reported before.

Acute Kidney Injury↗