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Biomedical subjects

D Katz

Publications and source records attributed to D Katz.

At least 37 records · Page 2Linked to original sources

Loss of orphan receptor germ cell nuclear factor function results in ectopic development of the tail bud and a novel posterior truncation.

The dynamic embryonic expression of germ cell nuclear factor (GCNF), an orphan nuclear receptor, suggests that it may play an important role during early development. To determine the physiological role of GCNF, we have generated a targeted mutation of the GCNF gene in mice. Germ line mutation of the GCNF gene proves that the orphan nuclear receptor is essential for embryonic survival and normal development. GCNF(-/-) embryos cannot survive beyond 10.5 days postcoitum (dpc), probably due to cardiovascular failure. Prior to death, GCNF(-/-) embryos suffer significant defects in posterior development. Unlike GCNF(+/+) embryos, GCNF(-/-) embryos do not turn and remain in a lordotic position, the majority of the neural tube remains open, and the hindgut fails to close. GCNF(-/-) embryos also suffer serious defects in trunk development, specifically in somitogenesis, which terminates by 8.75 dpc. The maximum number of somites in GCNF(-/-) embryos is 13 instead of 25 as in the GCNF(+/+) embryos. Interestingly, the tailbud of GCNF(-/-) embryos develops ectopically outside the yolk sac. Indeed, alterations in expression of multiple marker genes were identified in the posterior of GCNF(-/-) embryos, including the primitive streak, the node, and the presomitic mesoderm. These results suggest that GCNF is required for maintenance of somitogenesis and posterior development and is essential for embryonic survival. These results suggest that GCNF regulates a novel and critical developmental pathway involved in normal anteroposterior development.

Animals↗

The Trail Making Test: a study in focal lesion patients.

The relationship of the Trail Making Test (TMT) to the frontal lobes was tested by comparing patients with damage to the frontal and nonfrontal regions to control participants. Although the analysis of time measurements, both raw and transformed, showed notable slowing of frontal groups, error analysis proved to be a more useful method of categorizing performance. Analysis of errors on Part B indicated that all patients who made more than 1 error had frontal lesions. Dividing the frontal damaged patients into subgroups on the basis of the number of errors yielded specificity of brain-behavior relations within the frontal lobes. Patients with damage in dorsolateral frontal areas were most impaired. Those with inferior medial damage to the frontal lobes were not significantly affected in TMT Part B performance.

Adult↗

[Hyperprolactinemia in subclinical hypothyroidism].

Most patients with subclinical hypothyroidism are asymptomatic; however, when this disorder is associated with alterations of the lactotroph, clinical and biochemical manifestations are evident, along with involvement of the gonadotrophic function. In this report, we selected 11 women with hypothyroidism, 5 of them in stage I and 6 in stage II. In all of them, the thyroid function was altered while the most affected was the gonadal axis. The available literature on this subject is scarce, so that we propose a systematic investigation in order to exclude other associated disorders.

Adolescent↗

Retroperitoneal peripheral hemangioblastoma: a case report and review of the literature.

Central nervous system hemangioblastomas are uncommon tumors of controversial etiology that are usually found in the posterior fossa of the cranial cavity, retina, and spinal cord. Peripheral involvement is rare; only isolated case reports have been identified. We report an unusual case of hemangioblastoma involving the retroperitoneum. A 47-year-old African-American man presented with polycythemia on routine laboratory testing. Computed tomography revealed a large retroperitoneal mass near the pancreas, in a left suprarenal location, without adrenal involvement and without attachment to a nerve. Although hemangioblastoma may be associated with the von Hippel-Lindau syndrome, this patient did not have any of the stigmata of this disease. The histologic features included a highly vascular tumor with cellular areas composed of plump, pleomorphic spindled and epithelioid (stromal) cells with variable cytoplasmic lipid vacuoles and hypocellular areas with inflammatory cells and collagenous fibrils. Immunohistochemical staining showed that the tumor (stromal) cells were positive for vimentin, calponin, S-100 protein, neuron-specific enolase, and CD57 and negative for glial fibrillary acidic protein, cytokeratins, epithelial membrane antigen, CD34, HMB-45, desmin, and the actins. These morphologic and immunohistochemical findings are consistent with hemangioblastoma. To our knowledge this is the first reported case of a hemangioblastoma in this location. Based on this case we conclude that hemangioblastoma may occur in the retroperitoneum and outside of the central nervous system in a patient without von Hippel-Lindau syndrome. The immunoprofile of this case suggests that hemangioblastomas are mesenchymal neoplasms exhibiting both neural and myofibroblastic differentiation.

Hemangioblastoma↗

Lamellar corneal patch grafts in the management of corneal melting.

PURPOSE: To evaluate the clinical indications and results of reconstructive (tectonic) lamellar keratoplasty in corneal melting. METHODS: A nonrandomized, uncontrolled retrospective case series of 64 consecutive patients (80 eyes) who underwent lamellar keratoplasty for corneal melting at our institution over a 17-year period. We reviewed the (a) clinical indications, (b) visual acuities, (c) postoperative corneal clarity, and (d) post-operative complications. Comparisons in visual acuity were made between central and peripheral corneal melts. The statistical influence of patient age, diagnosis, and corneal graft size on pre- and postoperative visual acuity values also was studied. RESULTS: Although reconstructive lamellar keratoplasty for active corneal melting was effective in saving the integrity of the globes in all but four patients, the postoperative visual acuity remained poor in the majority of cases because of the often devastating nature of the underlying ocular diseases. Only 14 patients had best postoperative visual acuities of 20/100 or better. Repeated lamellar keratoplasties were necessitated by corneal opacification, infection, or progressive postoperative corneal dissolution in 14 cases. Subsequent vision-restoring surgeries, consisting of penetrating keratoplasties or cataract extractions, were done in 11 eyes with modest improvement of visual acuity. Postoperative visual acuity was significantly better in peripheral corneal melts than in central melts (p = 0.004). CONCLUSION: Lamellar keratoplasty is an effective method of restoring the integrity of the eye ravaged by corneal melting. It is less invasive and consequently safer than penetrating keratoplasty in actively inflamed and unstable eyes. The primary purpose for this surgery is to salvage the integrity of the globe during the acute phase of disease and not so much to achieve visual improvement per se. It allows time for systemic immunosuppression to take effect and for the eye to quiet down before possible future vision-restoring surgery.

Adult↗

Gamma ray nuclear resonance absorption: an alternative method for in vivo body composition studies.

We have evaluated gamma ray nuclear resonance absorption (gamma-NRA) on nitrogen, a mature technology proposed and developed by Soreq NRC for detecting explosives, as an alternative to neutron activation for in vivo assaying of body nitrogen. The principles of the gamma-NRA method are outlined, and a test facility constructed at McMaster University's Accelerator Laboratory is described. The results of a feasibility study recently performed there on phantoms and animal tissue are presented and discussed. gamma-NRA is a full imaging technique that essentially constitutes element-specific absorptiometry--i.e., it can generate projections of the mass distribution for a specific element, along with a conventional radiograph of the patient. From the transmission profile of an individual scanned by 9.17 MeV gamma rays, local or whole body nitrogen content can be determined via the resonant attenuation undergone when the beam encounters regions of nitrogen concentration. The advantages of gamma-NRA over neutron activation are (a) radiation doses delivered to the body are at least one order of magnitude lower, thus allowing repeated measurements on individual patients and also rendering the method ethically acceptable for application to children; (b) gamma-NRA is inherently free from uncertainties related to nonuniform distributions of the element in question within the body; (c) it is applicable to patients of varying size and shape; and (d) it yields both nitrogen images and conventional radiographic images of the body.

Animals↗

Relationship of peak height velocity to other maturity indicators in idiopathic scoliosis in girls.

BACKGROUND: Our aim was to compare height velocity data, obtained from clinical height measurements, for girls who had idiopathic scoliosis with the data for adolescents who did not have scoliosis. We also compared the growth data with chronological age, menarchal age, and Risser sign in terms of their accuracy in the prediction of growth and progression of the scoliosis. METHODS: One hundred and twenty of 371 patients in a database of girls managed with a brace for the treatment of idiopathic scoliosis had sufficient height data for us to quantify their growth peak. Height velocity data was generated from standing-height measurements obtained, in a scoliosis clinic, with a minimum six-month interval between measurements, and the timing of peak height velocity was calculated. The age at menarche was recorded from the patients' records. The Risser sign and Cobb angle were determined by a single observer. Progression of the scoliosis was defined as an increase in the Cobb angle of at least 10 degrees, compared with the curve magnitude at the time of the initial evaluation, after a minimum of six months. Progression to a magnitude requiring surgery was defined as progression of at least 10 degrees to a magnitude of 45 degrees or more. RESULTS: The height velocity plot grouped by peak height velocity showed a high peak and a sharp decline with values similar to those in normal populations. Extrapolating from percentile charts, 90 percent of our patients ceased growing by 3.6 years after peak height velocity. The growth peak was blunted (averaged over too long a period such that the data for the period of most rapid growth was averaged in with that for a period of slower growth) when chronological age, menarchal age, and Risser sign were used to predict growth; this indicated that these maturity scales grouped the patients poorly in terms of growth. The primary curve was progressive in eighty-eight of the 120 patients. Sixty of these patients had a curve of more than 30 degrees at peak height velocity, and in fifty (83 percent) of the sixty the curve progressed to 45 degrees or more. The remaining twenty-eight patients had a curve of 30 degrees or less at peak height velocity, with only one curve (4 percent) progressing to 45 degrees or more. Peak height velocity also grouped patients for maximal progression of the curve more accurately than did the other maturity scales, as most of the curves progressed maximally at peak height velocity. There was a wider spread of timing of maximal progression when chronological age, menarchal age, and Risser sign were used to predict progression. CONCLUSIONS: Height velocities generated from clinical height measurements for patients with idiopathic scoliosis document the growth peak and predict cessation of growth reliably. Knowing the timing of the growth peak provides valuable information on the likelihood of progression to a magnitude requiring spinal arthrodesis.

Adolescent↗

Differential effects of cisplatin in proximal and distal renal tubule epithelial cell lines.

Pathological studies suggest that cisplatin injures different portions of the nephron to different extents. To investigate this issue further, we examined the cytotoxicity and uptake of cisplatin in cell lines derived from S1 and S3 proximal tubule and distal convoluted tubule segments isolated from a mouse carrying the SV40 large T-antigen transgene. S1 cells displayed the highest sensitivity to cisplatin cytotoxicity, followed by S3 and distal convoluted tubule (DCT) cells. These differences in cytotoxicity did not correlate with differences in cisplatin uptake. Cytotoxic concentrations of cisplatin triggered apoptosis in all three cell lines. Although BAX and BCL-2 expression was similar among the three cell lines, the expression of the anti-apoptotic protein, BCL-X(L), was significantly lower in S1 cells than in S3 and DCT cells, and this may have contributed to the heightened sensitivity of S1 cells. Cisplatin transport characteristics demonstrated a saturable component of cisplatin uptake and differences in apparent K(M) and Vmax values among the three cell lines. The three cell lines were 43- to 176-fold more sensitive to cisplatin than to carboplatin. This distinction between the two drugs could not be fully explained by differences in the uptake rates of carboplatin and cisplatin. We conclude that cells from different portions of the nephron display different sensitivities to cisplatin, different transport characteristics for cisplatin and different levels of expression of BCL-X(L). In addition, the relative resistance of renal cells to carboplatin vs cisplatin is mostly due to the differential effects that follow internalization.

Animals↗

Enhanced DNA fragmentation in the thymus of spontaneously hypertensive rats.

The mechanisms contributing to organ injury in hypertension have been incompletely defined. The thymus gland of the spontaneously hypertensive rat (SHR) shows significant atrophy at the age of 15 wk compared with its normotensive control, the Wistar-Kyoto rat (WKY). The aim of the present study was to examine the thymus of SHR for evidence of DNA nicking as one of the mechanisms for thymic atrophy. SHR and WKY were subjected to adrenalectomy or sham surgery at 12 wk and studied at 15 wk. Adrenalectomy served to normalize the blood pressure in the SHR. DNA nicking was detected by in situ nick-end labeling (ISEL) of fixed tissue sections. Tissue sections were treated with proteolysis, and terminal deoxyribonucleotidyl transferase was used to incorporate biotinylated deoxynucleotides into DNA nick end in situ. Separately, DNA fragmentation was evaluated by measuring the level of released mono- and oligonucleosomes to the cytoplasm. A higher number of thymic ISEL-positive cells and a higher level of cytoplasmic mono- and oligonucleosomes were observed in SHR than in WKY. After adrenalectomy the enhanced level of ISEL and cytoplasmic mono- and oligonucleosomes in SHR was reduced to the level in WKY. Dexamethasone treatment (0.05 mg. kg-1. day-1) in WKY serves to decrease the thymus weight and significantly elevate the level of mono- and oligonucleosomes. Thus increased DNA fragmentation represents one of the mechanisms associated with thymic atrophy, a feature that reflects immune suppression in SHR.

Adrenalectomy↗

Low-grade monoclonal Epstein-Barr virus-associated lymphoproliferative disorder of the brain presenting as human immunodeficiency virus-associated encephalopathy in a child with acquired immunodeficiency syndrome.

The association of the Epstein-Barr virus with human immunodeficiency virus-associated primary central nervous system lymphomas is well known. We describe a pediatric patient infected with human immunodeficiency virus who developed a lesion in the central nervous system that appeared to be histologically reactive and that proved to be an Epstein-Barr virus-associated monoclonal B-cell lymphoproliferative disorder by molecular analysis. An 8-year-old girl was diagnosed with vertically transmitted human immunodeficiency virus infection at age 5, for which she was treated empirically with a combination of zidovudine and didanosine. At the age of 7 years, during evaluation for entry into an antiretroviral protocol, a single hypodense frontal lobe lesion was identified by computed tomography. After unsuccessful treatment for presumed toxoplasmosis and progressive neurologic deterioration, a stereotactic brain biopsy was performed. Although the biopsy contained a polymorphic lymphoid infiltrate that appeared to be cytologically reactive, polymerase chain reaction and in situ hybridization studies revealed a monoclonal Epstein-Barr virus-associated B-cell lymphoproliferative disorder, which was reminiscent of polymorphic B-cell hyperplasia observed in the setting of immunosuppression following organ transplantation. Postoperative therapy included steroids and antiretroviral therapy. The lesion decreased slightly in size, and the child's neurologic status was relatively unremarkable for 5 months. Subsequently, she developed cytomegalovirus retinitis, progressive encephalopathy, and died with pancytopenia. This case represents a newly described manifestation of Epstein-Barr virus-associated lymphoproliferative disorder, a diagnosis that should be considered in patients with neurologic symptoms and immunodeficiency. In addition, this case exhibited histologic features reminiscent of posttransplant lymphoproliferative disease, a histologic pattern that to our knowledge has not previously been reported in the setting of acquired immunodeficiency syndrome.

AIDS Dementia Complex↗

Prenatal lead exposure in Israel: an international comparison.

BACKGROUND: Prenatal lead exposure (umbilical cord blood lead concentration > 10 (micrograms/dl) may impair cognitive development. Childhood lead poisoning is infrequent in Israel, and there are no data on lead exposure in immigrants to Israel from the former Soviet Union. OBJECTIVES: To evaluate prenatal blood lead concentrations in Israeli newborns whose mothers were born in Israel and in those whose mothers recently immigrated from Russia, and to compare data of prenatal lead exposure in Israel with those reported from other countries. METHODS: We compared the UCBLC of 35 newborns of new immigrants from Russia with a group of 35 newborns whose mothers were born in Israel. Venous BLC was also measured in 50 mothers. Data are compared with similar reports on prenatal lead exposure internationally. RESULTS: The UCBLC in all 70 newborns (mean +/- SD) was 3.53 +/- 1.6 micrograms/dl, and mothers' BLC (mean +/- SD) was 3.90 +/- 1.39 micrograms/dl. UCBLC and BLC in the 50 mother-newborn pairs correlated (r = 0.36, P < 0.01). All newborns except one had UCBLC < 8.0 micrograms/dl. There was no significant difference between UCBLC in the two groups. CONCLUSIONS: Prenatal lead exposure among the study subjects in both groups was low. In this sample the newborns of mothers born in Israel and those whose mothers recently immigrated from Russia were not found to be at risk for lead poisoning. Prenatal lead exposure in this sample was low compared to that reported from various parts of the world.

Adult↗

Dysfunction of Ib (autogenic) spinal inhibition in patients with progressive supranuclear palsy.

We compared the activity of Ib spinal interneurons in five patients with progressive supranuclear palsy (PSP) with six age-matched control subjects. Stimulation of the medial gastrocnemius nerve at motor threshold intensity activated Ib afferents that in turn inhibit H reflexes from the soleus muscle. Maximum inhibition occurred at interstimulus intervals of 6 and 8 ms for both control subjects and PSP patients and was significantly greater in the PSP patients. Increased Ib activity of PSP patients may be caused by loss of inhibition of Ib interneurons through degeneration of the medullary reticulospinal pathway. The corticospinal pathways, unopposed by the medullary reticulospinal tract, may excessively activate Ib interneurons.

Afferent Pathways↗

Timing of onset of contraceptive effectiveness in Norplant implant users. Part I. Changes in cervical mucus.

OBJECTIVE: To provide scientific data regarding the changes in cervical mucus within the first hours to days after Norplant implant insertion and to estimate when the cervical mucus is hostile enough to suggest a contraceptive effect. DESIGN: Multicenter, clinical descriptive study. SETTING: Family planning clinics. PATIENT(S): Forty-two women who were between days 8 and 13 of their menstrual cycle and who had requested Norplant implants were admitted to the study. INTERVENTION(S): Cervical mucus and blood samples were obtained. MAIN OUTCOME MEASURE(S): Cervical mucus scores, sperm penetration distances, and serum levels of progesterone, estradiol, and levonorgestrel. RESULT(S): The median cervical mucus score observed at baseline was 6 ("fair"), indicating that the mucus was already somewhat hostile before insertion of the Norplant implants. The median scores declined to 5 at 12 and 24 hours and continued to decrease through day 7 to 2 ("poor"), a score that is judged as hostile to sperm penetration. Overall, 73% of all subjects had a poor cervical mucus score by 3 days after insertion; at 7 days after insertion, 90% exhibited poor mucus and none had a good score. There was a substantial drop in the overall median distance traveled by the vanguard sperm after 12 hours for each cervical mucus score grouping. The distance traveled decreased rapidly between 12 and 24 hours to < 0.5 cm in subjects with fair and poor mucus, and by day 3, 91% of the subjects exhibited poor sperm penetration. CONCLUSION(S): On the basis of our findings, deterioration of the quality of the cervical mucus and sperm penetration is evident by 24 hours after insertion, although not to a level that would suggest adequate protection until 72 hours after insertion. Therefore, we are confident in recommending that backup methods of contraception (e.g, condoms) need not be used for more than 3 days after insertion, even when the implants are inserted close to ovulation. These findings provide policy makers, clinic managers, and clinicians with important information about how they can improve client access to Norplant implants.

Adult↗

Static-electric field induction by a silicone cushion for the treatment of hypertrophic and keloid scars.

Silicone gel and silicone occlusive sheeting are widely used at present for the treatment of hypertrophic and keloid scars, without any scientific explanation as to their mode of action. In a recent paper the possibility was raised that static electricity generated by friction-activated silicone sheeting could be the reason for this effect, and that it can, with time, cause involution of hypertrophic and keloid scars. The objective of this study was to test this hypothesis and to observe whether a continuous and also an increased negatively charged static-electric field will shorten the treatment period. A device to implement these requirements gradually evolved over a 5-year period. A number of prototypes were tested until the final product was attained. Some of the patients in this study were treated initially with a silicone sponge inserted in the cushion. Later this version was changed to the final design described herein. A silicone cushion was developed with the purpose of increasing a negative static-electric charge to accelerate the regression process. The cushion is custom-made using a silicone occlusive sheeting envelope of 0.75-mm thickness, which does not deteriorate with use, and is partially filled with high viscosity silicone oil. Its edges are sealed, and its size is designed to extend a little beyond the scarred area. Static electricity readings, generated by activating the cushion by pumping action with the fingers, stretching or deforming the cushion, are invariably much higher when compared with those obtained with silicone occlusive sheeting and silicone gel sheeting. The interaction between the negatively charged ions of the cushion and the ionic charges of the tissue fluids may be the critical factor in achieving hypertrophic and keloid scars involution. Of the 30 patients enrolled in the study, 3 patients dropped out. Treatment with the silicone cushions yielded 63.3 percent cessation of itching and burning followed by pallor and flattening of the scar, some markedly so, over a few weeks to 6-month period. An additional 26.6 percent had their scars resolved in up to 12 months of treatment. Good contact of the cushion over the scar has been shown to be important in this clinical trial, and much creativity is needed for making elastic strap bindings that ensure this contact. The clinical trials extended over a 12-month period. Ten patients (33.3 percent) who had recalcitrant scars with little response to the use of the silicone cushion were given intralesional corticosteroid injections, in addition to the continued use of the cushion, resulting in a fairly rapid resolution of these scars over a period of months to a year.

Adolescent↗