bluuebunny/crossref_metadata_2025 huggingface dataset:
A multicenter Phase II study of the intravenous administration of liposomal tretinoin in patients with acquired immunodeficiency syndrome‐associated Kaposi's sarcoma
Authors: Bernstein Zale P. , Chanan‐Khan Asher , Miller Kena C. , Northfelt Donald W. , Lopez‐Berestein Gabriel , Gill Parkash S.
Published: December 2002

BACKGROUND

A multicenter trial was conducted to determine the efficacy and toxicity of escalating dosages of liposomal tretinoin (all‐trans‐retinoic acid) administered once or three times weekly in patients with acquired immunodeficiency syndrome (AIDS)‐associated Kaposi sarcoma.

METHODS

Seventy‐six patients with acquired immunodeficiency syndrome (AIDS)‐associated Kaposi sarcoma were randomized to receive the study drug either once (n = 30) or 3 times weekly (n = 46). The starting dosage was 60 mg/m2, which was escalated to 90 mg/m2 and then 120 mg/m2 if the drug was well tolerated (≤ Grade 2 toxicities [according to the Southwest Oncology Group toxicity scale]). Four weeks of therapy constituted 1 cycle; patients could receive up to 8 cycles and those who completed 8 cycles were given the option of receiving extended therapy. Clinical response was defined as complete response (CR), partial response (PR), or stable disease (SD).

RESULTS

Efficacy was assessed after the completion of 3 treatment cycles; 28.9% of patients (22 of 76 patients) responded (no CRs, 1 PR, and 21 SDs). Among the patients receiving treatment 3 times weekly, 16 of 49 patients (32.7%) achieved a clinical response at the end of the third treatment cycle (no CRs, 1 PR, and 15 SDs). Concomitant or prior use of protease inhibitors did not appear to affect the patient's response to treatment (P = 0.183).

CONCLUSIONS

Liposomal tretinoin is a new therapeutic agent that has been reported to have some clinical activity in patients with AIDS‐associated Kaposi sarcoma. A three‐times‐per‐week dosing schedule was noted to be more effective compared with a once‐a‐week schedule without any significant difference in toxicity reported. Cancer 2002;95:2555–61. © 2002 American Cancer Society.

DOI 10.1002/cncr.11009
Study of transport properties co – evaporated lead telluride (PbTe) thin films
Authors: Khairnar U.P. , Pawar P.H. , Bhavsar G.P.
Published: December 2002

Thin films of lead telluride (PbTe) of thicknesses ranging from 1000 Å to 2500 Å have been prepared by co‐evaporation (three temperature) technique, onto precleaned amorphous glass substrates at various temperatures. The deposited samples were annealed and annealed samples were used for characterization. Resistivity of these samples was measured by four‐probe technique as a function of thickness and temperature. Activation energy for charge transport have been evaluated and found in the range of 0.09 to 0.106 eV. Thermoelectric power has been measured and found to be positive indicating that the samples are p‐type semiconducting material. Mobility variation with temperature has been estimated (evaluated) and correlated with scattering mechanism in the entire range of temperature studied. The X‐ray diffraction analysis confirmed that films are polycrystalline having cubic structure cell and lattice parameters are reported.
Effects of nateglinide and glibenclamide on postprandial lipid and glucose metabolism in type 2 diabetes
Authors: Vakkilainen Juha , Mero Niina , Schweizer Anja , Foley James E. , Taskinen Marja‐Riitta
Published: December 2002

Background

Postprandial hyperlipemia and small, dense LDL particles are features of dyslipidemia in type 2 diabetes. The purpose of this study was (1) to determine whether the oral insulinotropic drugs, nateglinide and glibenclamide, can overcome the defect of insulin action to suppress the hepatic VLDL release after a meal and decrease the postprandial lipemia and (2) to evaluate the acute effect of postprandial hypertriglyceridemia on LDL particle size in subjects with type 2 diabetes.

Methods

Forty‐three subjects with type 2 diabetes and mean baseline HbA1c 7.6% (95% CI 7.3 to 7.9) were treated with nateglinide 120 mg three times daily or glibenclamide 5 mg once or twice daily for 12 weeks in a double‐blind randomised trial. Insulin, glucose, and lipoprotein responses to a mixed fat‐rich meal were determined for 8 h postprandially at baseline and at 12 weeks on‐trial.

Results

Nateglinide and glibenclamide significantly augmented the maximal response in serum insulin at 60 min postprandially compared with the response without the drug [additional increase 25.0 mU/l (95% CI 11.2–38.8) p = 0.001 and 12.5 mU/l (95% CI 4.6–20.3) p = 0.003, respectively] and reduced hyperglycemia. Neither drug affected fasting or postprandial lipid or lipoprotein levels. LDL size did not significantly change in the 8‐h postprandial period.

Conclusions

Although nateglinide and glibenclamide increase postprandial insulin secretion and attenuate hyperglycemia, they do not alleviate postprandial lipemia in subjects with type 2 diabetes and good glycemic control. Although small LDL particle size is associated with chronic hypertriglyceridemia, LDL size does not change during acute postprandial hypertriglyceridemia. Copyright © 2002 John Wiley & Sons, Ltd.
Normal renal function 8 to 13 years after Cyclosporin A therapy in 285 diabetic patients
Authors: Assan Roger , Blanchet Françoise , Feutren Gilles , Timsit José , Larger Etienne , Boitard Christian , Amiel Claude , Bach Jean‐François
Published: December 2002

Background

Cyclosporin A (CyA) may induce acute nephrotoxicity. The question has been raised of the possible long‐term unfavorable course of CyA‐induced lesions. Advantage was taken of a large cohort of diabetic patients treated for several months using moderate CyA dosage to evaluate the long‐term evolution of renal function in such patients.

Methods

Two hundred and eighty five recently diagnosed type 1 diabetic patients having received CyA for a mean of 19.9 months were monitored for 13 years, in parallel with 100 similar patients treated with insulin alone.

Results

In the CyA‐treated group, a transient increase in creatininemia levels occurred during the first 18 months of treatment associated with a transient increase in renal vascular resistance. Both effects disappeared later on: creatininemia levels then remained normal. Inulin and p‐aminohippurate (PAH) clearances remained normal throughout follow‐up. Neither permanent renal failure nor progressive deterioration of renal function occurred in either group or in individual patients. A 10 to 12% increase in inulin and PAH clearance was elicited by IV amino acid infusion at 7 to 10 years, a finding consistent with a normal renal functional reserve. Patients with moderate kidney lesions on biopsy at 1 year had normal and stable clearance values at 7 to 13 years. The prevalence of arterial hypertension and retinopathy was lower in the CyA‐treated group than in the control group, possibly because of the tighter metabolic control obtained in the CyA group.

Conclusion

These results suggest that low‐dose CyA treatment combined with thorough monitoring does not result in long‐term renal dysfunction. Copyright © 2002 John Wiley & Sons, Ltd.
Impaired glucose tolerance and insulinopenia in the GK‐rat causes peripheral neuropathy
Authors: Murakawa Yuichi , Zhang Weixian , Pierson Christopher R , Brismar Tom , Östenson Claes‐Göran , Efendic Suad , Sima Anders A. F.
Published: December 2002

Background

Recent studies indicate that impaired glucose tolerance (IGT) in man is a causative factor in idiopathic sensory neuropathy, and that insulinopenia may contribute substantially to the severity of diabetic peripheral neuropathy. The effect of sustained IGT and progressive insulinopenia in the absence of overt hyperglycemia on peripheral nerve abnormalities was examined in the Goto–Kakizaki (GK)‐rat.

Methods

Two and eighteen‐month‐old GK rats with decreased glucose tolerance and overt insulinopenia, respectively, were examined with respect to nerve function, structure, morphometry and molecular integrity, and were compared to age‐matched control rats.

Results

Both 2‐(p < 0.001) and 18‐month‐old (p < 0.001) GK rats showed reduced body weight. Blood glucose levels following glucose tolerance tests were elevated in both the 2‐month and the 18‐month‐old GK rats. Fasting plasma insulin levels in the 2‐month GK rats were increased threefold (p < 0.05) but decreased by 71% (p < 0.001) in the 18‐month GK rats. The two‐month GK rats showed a normal nerve conduction velocity, whereas in the 18‐month GK rats it was reduced to 76% (p < 0.001) of control values. No morphometric abnormalities were found in the 2‐month GK rats, whereas the 18‐month GK rats showed loss of small myelinated fibers (p < 0.001), atrophy and loss of unmyelinated axons (p < 0.05) and an increased (p < 0.01) frequency of regenerating fibers. In the older GK rats, both mRNA and protein expression of nerve growth factor (NGF) in the sciatic nerve were significantly reduced (p < 0.001 and p < 0.05), and NGFR TrkA (high affinity NGF receptor) and NGFRp75 (low affinity NGF‐receptor) protein expression was reduced in dorsal root ganglia (DRG) (both p < 0.05). These changes were accompanied by significantly reduced protein expressions of substance P (SP) and calcitonin gene–related protein (CGRP) in DRG's (both p < 0.001) as well as a 40% (p < 0.001) decrease in SP and a 62% (p < 0.001) decrease in CGRP‐positive DRG neurons. In the sciatic nerve, SP and CGRP protein expression was decreased by 71% (p < 0.01) and 79% (p < 0.01), respectively.

Conclusion

IGT combined with hyperinsulinemia for 2 months have no detectable effect on peripheral nerve function or structure. In contrast, IGT and subsequent insulinopenia result in a functional and structural neuropathy associated with impaired NGF support and neuropeptide synthesis. We suggest that these abnormalities are mainly due to insulinopenia rather than hyperglycemia. Copyright © 2002 John Wiley & Sons, Ltd.
Therapy of type 2 diabetes mellitus based on the actions of glucagon‐like peptide‐1
Authors: Holst Jens Juul
Published: December 2002

GLP‐1 is a peptide hormone from the intestinal mucosa. It is secreted in response to meal ingestion and normally functions in the so‐called ileal brake, that is, inhibition of upper gastrointestinal motility and secretion when nutrients are present in the distal small intestine. It also induces satiety and promotes tissue deposition of ingested glucose by stimulating insulin secretion. Thus, it is an essential incretin hormone. In addition, the hormone has been demonstrated to promote insulin biosynthesis and insulin gene expression and to have trophic effects on the beta cells. The trophic effects include proliferation of existing beta cells, maturation of new cells from duct progenitor cells and inhibition of apoptosis. Furthermore, glucagon secretion is inhibited. Because of these effects, the hormone effectively improves metabolism in patients with type 2 diabetes mellitus. Thus, continuous subcutaneous administration of the peptide for six weeks in patients with rather advanced disease greatly improved glucose profiles and lowered body weight, haemoglobin A1C, and free fatty acids (FFA). In addition, insulin sensitivity doubled and insulin responses to glucose were greatly improved. There were no side effects. Continuous administration is necessary because of rapid degradation by the enzyme dipeptidyl peptidase‐IV. Alternative approaches include the use of analogues that are resistant to the actions of the enzyme, as well as inhibitors of the enzyme. Both approaches have shown remarkable efficacy in both experimental and clinical studies. The GLP‐1‐based therapy of type 2 diabetes, therefore, represents a new and attractive alternative. Copyright © 2002 John Wiley & Sons, Ltd.
Glucose‐stimulated signaling pathways in biphasic insulin secretion
Authors: Straub Susanne G. , Sharp Geoffrey W. G.
Published: December 2002

Glucose‐stimulated biphasic insulin secretion involves at least two signaling pathways, the KATP channel‐dependent and KATP channel‐independent pathways, respectively. In the former, enhanced glucose metabolism increases the cellular adenosine triphosphate/adenosine diphosphate (ATP/ADP) ratio, closes KATP channels and depolarizes the cell. Activation of voltage‐dependent Ca2+ channels increases Ca2+ entry and [Ca2+]i and stimulates insulin release. The KATP channel‐independent pathways augment the response to increased [Ca2+]i by mechanisms that are currently unknown. However, they affect different pools of insulin‐containing granules in a highly coordinated manner. The β‐cell granule pools can be minimally described as reserve, morphologically docked, readily and immediately releasable. Activation of the KATP channel‐dependent pathway results in exocytosis of an immediately releasable pool that is responsible for the first phase of glucose‐stimulated insulin release. Following glucose metabolism, the rate‐limiting step for the first phase lies in the rate of signal transduction between sensing the rise in [Ca2+]i and exocytosis of the immediately releasable granules. The immediately releasable pool of granules can be enlarged by previous exposure to glucose (by time‐dependent potentiation, TDP), and by second messengers such as cyclic adenosine monophosphate (cyclic AMP) and diacylglycerol (DAG). The second phase of glucose‐stimulated insulin secretion is due mainly to the KATP channel‐independent pathways acting in synergy with the KATP channel‐dependent pathway. The rate‐limiting step here is the conversion of readily releasable granules to the state of immediate releasability, following which, in an activated cell they will undergo exocytosis. In the rat and human β‐cell the KATP channel‐independent pathways induce a time‐dependent increase in the rate of this step that results in the typical rising second‐phase response. In the mouse β‐cell the rate appears not to be changed much by glucose. Potential intermediates involved in controlling the rate‐limiting step include increases in cytosolic long‐chain acyl‐CoA levels, adenosine triphosphate (ATP) and guanosine triphosphate (GTP), DAG binding proteins, including some isoforms of protein kinase (PKC), and protein acyl transferases. Agonists that can change the rate‐limiting steps for both phases of insulin release include those like glucagon‐like peptide 1 (GLP‐1) that raise cyclic AMP levels and those like acetylcholine that act via DAG. Copyright © 2002 John Wiley & Sons, Ltd.
Glucose‐responsive insulin‐producing cells from stem cells
Authors: Kaczorowski David J. , Patterson Ethan S. , Jastromb William E. , Shamblott Michael J.
Published: December 2002

Recent success with immunosuppression following islet cell transplantation offers hope that a cell transplantation treatment for type 1 (juvenile) diabetes may be possible if sufficient quantities of safe and effective cells can be produced. For the treatment of type 1 diabetes, the two therapeutically essential functions are the ability to monitor blood glucose levels and the production of corresponding and sufficient levels of mature insulin to maintain glycemic control. Stem cells can replicate themselves and produce cells that take on more specialized functions. If a source of stem cells capable of yielding glucose‐responsive insulin‐producing (GRIP) cells can be identified, then transplantation‐based treatment for type 1 diabetes may become widely available. Currently, stem cells from embryonic and adult sources are being investigated for their ability to proliferate and differentiate into cells with GRIP function. Human embryonic pluripotent stem cells, commonly referred to as embryonic stem (ES) cells and embryonic germ (EG) cells, have received significant attention owing to their broad capacity to differentiate and ability to proliferate well in culture. Their application to diabetes research is of particular promise, as it has been demonstrated that mouse ES cells are capable of producing cells able to normalize glucose levels of diabetic mice, and human ES cells can differentiate into cells capable of insulin production. Cells with GRIP function have also been derived from stem cells residing in adult organisms, here referred to as endogenous stem cell sources. Independent of source, stem cells capable of producing cells with GRIP function may provide a widely available cell transplantation treatment for type 1 diabetes. Copyright © 2002 John Wiley & Sons, Ltd.
Laxative misuse and behavioral disinhibition in bulimia nervosa
Authors: Bruce Kenneth R. , Koerner Naomi M. , Steiger Howard , Young Simon N.
Published: December 2002

Objective

Various reports suggest that purging with laxatives is associated with greater behavioral impulsivity in bulimia nervosa (BN) patients. We investigated the extent to which laxative misuse corresponds to specific impulse‐control problems.

Method

Participants included bulimic women who misuse laxatives (BNL+; n = 12), bulimic women who do not misuse laxatives (BNL−; n = 33), and healthy normal eaters (NE; n = 26). Participants completed the Go/No‐Go discrimination task (a well‐validated computerized measure of response disinhibition), as well as self‐report questionnaires of impulsivity, eating symptoms, and general psychopathology.

Results

Compared with the other groups, the BNL+ group made more commission errors on the Go/No‐Go under cues for punishment, indicating they were more disinhibited when faced with possible negative outcomes. Compared with the BNL− group, the BNL+ group was also more likely to differ from the NE group on self‐reported impulsivity. There were no differences between the two bulimic groups on eating symptoms and the three groups did not differ in terms of general psychopathology.

Discussion

Findings suggest that, controlling for eating symptoms and psychopathology, laxative misuse among BN patients is associated with difficulty inhibiting incorrect responses in the face of perceived threats. © 2002 by Wiley Periodicals, Inc. Int J Eat Disord 33: 92–97, 2003.
A T‐LCLC type immittance converter
Authors: Irie Hisaichi , Kisimoto Haruki
Published: December 2002

“Immittance converter” is short for “impedance–admittance converter.” The immittance converter has an input impedance that is proportional to the admittance of the load connected across output terminals. In this converter, the output current is proportional to the input voltage and the input current is proportional to the output voltage. Consequently, it converts a constant voltage source into a constant current source and a constant current source into a constant voltage source.

It is well known that the quarter‐wavelength transmission line shows immittance conversion characteristics. However, it has very long line length for the switching frequency, and is not suitable for power electronics application. Thus, we proposed immittance converters that consist of lumped elements L, C and show improved immittance conversion characteristics at a resonant frequency. In this paper, we propose a T‐LCLC‐type immittance converter, which has the transitive configuration and both advantages of T‐LCL‐ and π‐CLC‐type immittance converters. We show voltage–current transformation characteristics and frequency characteristics and efficiency characteristics of the T‐LCLC immittance converter. These characteristics were determined analytically and experimentally. © 2002 Wiley Periodicals, Inc. Electr Eng Jpn, 142(3): 57–63, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/eej.10095
Inducible site‐specific recombination in myelinating cells
Authors: Doerflinger Nathalie H. , Macklin Wendy B. , Popko Brian
Published: December 2002

Summary: To explore the function of genes expressed by myelinating cells we have developed a model system that allows for the inducible ablation of predetermined genes in oligodendrocytes and Schwann cells. The Cre/loxP recombination system provides the opportunity to generate tissue‐specific somatic mutations in mice. We have used a fusion protein between the Cre recombinase and a mutated ligand‐binding domain of the human estrogen receptor (CreERT) to obtain inducible, site‐specific recombination. CreERT expression was placed under the transcriptional control of the regulatory sequences of the myelin proteolipid protein (PLP) gene, which is abundantly expressed in oligodendrocytes and to a lesser extent in Schwann cells. The CreERT fusion protein translocated to the nucleus and mediated the recombination of a LacZ reporter transgene in myelinating cells of PLP/CreERT mice injected with the synthetic steroid tamoxifen. In untreated animals CreERT remained cytoplasmic, and there was no evidence of recombination. The PLP/ CreERT animals should be very useful in elucidating and distinguishing a particular gene's function in the formation and maintenance of the myelin sheath and in analyzing mature oligodendrocyte function in pathological conditions. genesis 35:63–72, 2003. © 2002 Wiley‐Liss, Inc.
Cre‐loxp fate‐mapping of Pax6 enhancer active retinal and pancreatic progenitors
Authors: Zhang Xin , Heaney Shaun , Maas Richard L.
Published: December 2002

Summary: Pax6 plays important roles in the control of ocular and pancreatic development. We identified a 450 bp Pax6 enhancer that contains two interacting sequences: a 274 bp fragment sufficient for expression in retinal progenitors and an adjacent 156 bp fragment required for expression in pancreatic progenitors. Since this enhancer is only transiently expressed during embryogenesis, a Cre‐loxP fate‐mapping strategy was used to investigate the developmental potential of these progenitors. Surprisingly, the labeled retinal precursors predominantly gave rise to horizontal cells, indicating a cell lineage role in horizontal cell differentiation. In the pancreas, all enhancer‐specific cells were restricted to endocrine and ductal cell lineages. This result lends support to a model whereby Pax6‐expressing progenitors contribute to the adult pancreatic islets and ducts. The progenitor cell‐specificity of this enhancer will be useful in studies that require either cell‐specific expression or conditional gene inactivation in these cell populations. genesis 35:22–30, 2003. © 2002 Wiley‐Liss, Inc.
The proto‐oncogene BCL‐6 in normal and malignant B cell development
Authors: Niu Huifeng
Published: December 2002

BCL‐6 is an important regulator of the immune system. It is required for GC formation and T cell dependent antibody responses. Mice deficient in BCL‐6 fail to form GC and mount reduced levels of T cell‐dependent antibody responses. BCL‐6 (−/−) mice, in addition, develop a massive inflammatory response in many organs characterized by eosinophilic infiltration and hyper‐IgE production, a typical Th2 hyperimmune response. This suggests a negative role of BCL‐6 in Th2 pathway. The BCL‐6 gene encodes a POZ/zinc finger transcription repressor highly expressed in GC B cells, but not in pre‐GC B cells or in more differentiated memory or plasma cells. By functioning as a potent transcriptional repressor of various target genes, BCL‐6 modulates IL‐4, BCR, and CD40L signals for normal B cell development. In B cell lymphomas, structural alterations of the BCL‐6 promoter region, including chromosome translocation and somatic hypermutation, represent the most frequent genetic lesions associated with non‐Hodgkin lymphoma, especially of diffuse large cell lymphoma, a malignancy often derived from germinal centre (GC) B cells. This suggests that deregulated expression of BCL‐6 may contribute to lymphomagenesis. Copyright © 2002 John Wiley & Sons, Ltd.
Hypermethylation of gene promoters in hematological neoplasia
Authors: Chim C. S. , Liang R. , Kwong Y. L.
Published: December 2002

Cancer cells are associated with global hypomethylation but with focal hypermethylation of specific gene promoters organized as CpG island. DNA methyltransferases, DNMT1 and 3 (3a and 3b), have been implicated in mediating maintenance and de novo methylation. Hypermethylation of gene promoters results in the inactivation of the corresponding genes, by preclusion of the formation of the transcription complex, due to the recruitment of MBP, MeCPs and histone deacetylase. This results in the deacetylation of histone and thus a compact chromatin complex unfavourable for the initiation of transcription. This methylation‐associated gene silencing has been demonstrated in various genes including tumour suppressor genes (p15, p16, p73, VHL). Therefore, gene promoter hypermethylation collaborates with other mechanisms of gene inactivation such as deletion and intragenic mutations to fulfil Knudson's hypothesis. Hypermethylation may serve as a molecular disease marker for the detection of minimal residual disease. Emerging evidence suggests a possible prognostic value of gene promoter hypermethylation. Moreover, gene hypermethylation may also serve as a target for therapeutic invention by hypomethylating agents. Copyright © 2002 John Wiley & Sons, Ltd.
Characteristics and survival of patients with non‐Hodgkin's lymphoma with and without acquired immunodeficiency syndrome
Authors: Diamond Catherine , Taylor Thomas H. , Anton‐Culver Hoda
Published: December 2002

Our objective was to determine the characteristics and survival of patients with non‐Hodgkin's lymphoma (NHL) with and without acquired immunodeficiency syndrome (AIDS). A cancer registry and AIDS registry linkage for San Diego County was performed in October 1998 as part of a national multicentre study. We performed Kaplan–Meier analysis to compare survival in NHL patients with and without AIDS, after matching for age, sex, and race/ethnicity. We performed logistic regression to determine which patient and tumour characteristics were significantly associated with 1‐year survival. Of the 4361 cases of NHL, 324 (7%) had AIDS and 4037 (93%) were not known to have AIDS. Patients with AIDS were more likely to have extranodal, high‐grade, and disseminated NHL diagnosed by non‐histologic means and were less likely to have received chemotherapy. Patients with AIDS and NHL who survived at least 1 year had less advanced disease stage and received chemotherapy. The median survival in patients with AIDS was 4 months (95% confidence interval (CI): 4–5) and 95 months (95% CI: 58–157) in patients without AIDS (P<0.001). Although these patients with AIDS‐related NHL were unlikely to survive, the highly active antiretroviral agents currently used may improve outcomes in future patients. Copyright © 2002 John Wiley & Sons, Ltd.
Adding more observations to saturated D‐optimal resolution III two‐level factorial designs
Authors: Hedayat A. S. , Zhu Haiyuan
Published: December 2002

We consider the class of saturated main effect plans for the 2k factorial. With these saturated designs, the overall mean and all main effects can be unbiasedly estimated provided that there are no interactions. However, there is no way to estimate the error variance with such designs. Because of this and other reasons, we like to add some additional runs to the set of (k+1) runs in the D‐optimal design in this class. Our goals here are: (1) to search for s additional runs so that the resulting design based on (k+s+1) runs yields a D‐optimal design in the class of augmented designs; (2) to classify all the runs into equivalent classes so that the runs in the same equivalent class give us the same value of the determinant of the information matrix. This allows us to trade runs for runs if this becomes necessary; (3) to obtain upper bounds for determinant of the information matrices of augmented designs. In this article we shall address these approaches and present some new results. © 2002 Wiley Periodicals, Inc. J Combin Designs 11: 51–77, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jcd.10026
New type of block design
Authors: Mendelsohn N. S. , Liang M.
Published: December 2002

We are already familiar with (υ, k, λ)‐difference sets and (υ, k, λ)‐designs. In this paper, we will introduce a new class of difference sets and designs: (υ, k, [λ1, λ2, … , λm])‐difference sets and (υ, k, [λ1,λ2, … , λm])‐designs. We will mainly study designs with a relationship we call λ‐equivalence and use them to produce other designs. Some existence or nonexistence theorems will be given. © 2002 Wiley Periodicals, Inc. J Combin Designs 11: 1–23, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jcd.10031
Further results on large sets of disjoint group‐divisible designs with block size three and type 2n41
Authors: Cao H. , Lei J. , Zhu L.
Published: December 2002

Large sets of disjoint group‐divisible designs with block size three and type 2n41 were first studied by Schellenberg and Stinson because of their connection with perfect threshold schemes. It is known that such large sets can exist only for n ≡0 (mod 3) and do exist for all odd n ≡ (mod 3) and for even n=24m, where m odd ≥ 1. In this paper, we show that such large sets exist also for n=2k(3m), where m odd≥ 1 and k≥ 5. To accomplish this, we present two quadrupling constructions and two tripling constructions for a special large set called *LS(2n). © 2002 Wiley Periodicals, Inc. J Combin Designs 11: 24–35, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jcd.10032
Slope packings and coverings, and generic algorithms for the discrete logarithm problem
Authors: Chateauneuf M. , Ling A. C. H. , Stinson D. R.
Published: December 2002

We consider the set of slopes of lines formed by joining all pairs of points in some subset S of a Desarguesian affine plane of prime order p. If all the slopes are distinct and non‐infinite, we have a slope packing; if every possible non‐infinite slope occurs, then we have a slope covering. We review and unify some results on these problems that can be derived from the study of Sidon sets and sum covers. Then we report some computational results, we have obtained for small values of p. Finally, we point out some connections between slope packings and coverings and generic algorithms for the discrete logarithm problem in prime order (sub)groups. Our results provide a combinatorial characterization of such algorithms, in the sense that any generic algorithm implies the existence of a certain slope packing or covering, and conversely. © 2002 Wiley Periodicals, Inc. J Combin Designs 11: 36–50, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jcd.10033
Supraspinal connections of the ovary: Structural and functional aspects
Authors: Gerendai Ida , Kocsis Katalin , Halász Béla
Published: December 2002

This review summarizes our recent studies using the viral transneuronal tracing technique to identify sites in the central nervous system (CNS) that are connected with the ovary. A neurotropic virus (pseudorabies virus) was injected into the ovary and various times after the inoculation the spinal cord and brain were examined for virus‐infected neurons identified by immunocytochemistry. Such neurons could be detected in well‐defined cell groups of the spinal cord (intermediolateral cell column), brain stem (vagal nuclei, area postrema, parapyramidal nucleus, caudal raphe nuclei, A1, A5, A7 noradrenergic cell groups, locus coeruleus, Barrington's nucleus, periaqueductal gray), hypothalamus (paraventricular nucleus, anterior hypothalamus, arcuate nucleus, zona incerta), and, at longer survival time, in some telencephalic structures (amygdala, bed nucleus of the stria terminalis). These findings provided the first neuromorphological evidence for the existence of a multisynaptic neuronal pathway between the brain and the ovary presumably involved in the neuronal control of the organ. The observations indicate that there is a significant overlap of CNS structures connected with the ovary, the testis, other organs and organ systems, suggesting similar neuronal circuitries of the autonomic nervous system innervating the different organs. The known descending neuronal connections between the CNS structures labeled from the ovary by the viral transneuronal tracing technique and the findings suggesting a pituitary independent interplay between certain cerebral structures such as the hypothalamus, the amygdala, and the ovary are also summarized in this review. Microsc. Res. Tech. 59:474–483, 2002. © 2002 Wiley‐Liss, Inc.
Localization of calretinin in the rat ovary and in relation to nerve cell bodies in dorsal root and paravertebral ganglia projecting to the ovary
Authors: Burden Hubert W. , Zary Joan T.
Published: December 2002

Retrograde tracing with True Blue was combined with immunocytochemistry to determine the source of any calretinin‐immunoreactive (CR‐ir) nerves projecting to the rat ovary. In the ovary, a strong signal for calretinin immunoreactivity was localized in interstitial gland cells; however, no intraovarian CR‐ir nerves could be demonstrated. When the superior ovarian nerve was isolated, cut, and True Blue applied to the proximal end, the fluorescent dye was retrogradely transported to a population of cells located in T‐12, T‐13, and L‐1 dorsal root and paravertebral ganglia. There was virtually no dual labeling of cells in these ganglia with calretinin (< 0.009% dual labeling in dorsal root and <0.014% in paravertebral ganglia). However, greater than two‐thirds of the True Blue‐labeled cells were immediately adjacent to CR‐ir cells in dorsal root ganglia. This arrangement is suggestive of a paracrine mechanism between CR‐ir cells and cells projecting to the ovary. In paravertebral ganglia, 63% of cells projecting to the ovary were surrounded completely or partially by beaded CR‐ir nerve fibers. The source of these fibers (sensory or preganglionic sympathetic) is unknown but hypothesized to be preganglionic. Collectively, these observations suggest a participatory role for calretinin in ovarian function, either directly via effects on the interstitial gland or indirectly by influencing neurons projecting to the ovary. Microsc. Res. Tech. 59:490–494, 2002. © 2002 Wiley‐Liss, Inc.
Neurotrophic control of ovarian development
Authors: Dissen Gregory A. , Romero Carmen , Paredes Alfonso , Ojeda Sergio R.
Published: December 2002

Substantial evidence now exists indicating that the neurotrophins, a family of growth factors required for the survival, development, and differentiation of various neuronal populations of the nervous system, are also important for the development of nonneuronal tissues. Such a function was first suggested by studies showing the presence of high‐affinity neurotrophin receptors in a variety of nonneuronal tissues including those of the cardiovascular, endocrine, immune, and reproductive systems. Within the latter, the gonads appear to be a preferential site of neurotrophin action as suggested by the presence in the mammalian ovary of at least four of the five known neurotrophins and all of the neurotrophin receptors thus far identified. While the various functions that the neurotrophins may have in the ovary are still being elucidated, it is now clear that in addition to recruiting the ovarian innervation, they play a direct role in the regulation of two different maturational periods that are critical for the acquisition of female reproductive function: early follicular development and ovulation. Neurotrophins facilitate the development of newly formed follicles by promoting the initial differentiation and the subsequent growth of primordial follicles. These actions appear to be related to the ability of neurotrophins to sustain the proliferation of both mesenchymal and granulosa cells, and to induce the synthesis of follicle stimulating hormone (FSH) receptors. At the time of the first ovulation, neurotrophins contribute to the ovulatory cascade by increasing prostaglandin E2 release, reducing gap junction communication, and inducing cell proliferation within the thecal compartment of preovulatory follicles. Microsc. Res. Tech. 59:509–515, 2002. © 2002 Wiley‐Liss, Inc.
Ovarian acetylcholine and muscarinic receptors: Hints of a novel intrinsic ovarian regulatory system
Authors: Mayerhofer Artur , Fritz Stephanie
Published: December 2002

More than two decades ago, the degrading enzyme of the neurotransmitter acetylcholine (ACH) was reported in nerve fibers of the rat ovary. Subsequently, it was assumed that ACH is a neurotransmitter of ovarian nerves, although the sole presence of the degrading enzyme, ACH‐esterase, does not allow such a conclusion. That ACH may be involved in the complex regulation of ovarian functions, including hormone production, was indicated by studies using, for example, granulosa cells (GCs). The lack of detailed information about both source(s) and functions of ACH in the ovary prompted us to examine sites of ovarian ACH‐synthesis and ACH‐receptor‐bearing target cells. We also started to identify functions of ACH in cultured human GCs. While ovarian innervation and recently described neuron‐like cells of the ovary were not immunoreactive for the ACH‐synthesizing enzyme, choline‐acetyl transferase (CHAT), we found immunoreactivity in GCs of rodents and primates. Isolated human and rat GCs produced ACH and contained the vesicular ACH transporter (VACHT). These results indicate that endocrine GCs are an unexpected non‐neuronal source of ACH in the ovary. Moreover, these cells and GCs in vivo contain ACH‐receptors of the muscarinic subtype (MR), namely M1R and M5R. In contrast, oocytes express M3R. MR of human GCs are functional and cholinergic stimulation is linked to rapid increases in intracellular Ca++ levels. M1/5R activation also led to increased cell proliferation of human GCs in vitro and this stimulatory effect was found to be associated with rapid disruption of gap junction communication. Ongoing studies begin to identify regulation of ion channels and altered gene expression as consequences of MR stimulation. Thus, our results outline first details of an unexpected intraovarian, non‐neuronal cholinergic system, and suggest that it may be involved in the regulation of cell proliferation in the ovary. Microsc. Res. Tech. 59:503–508, 2002. © 2002 Wiley‐Liss, Inc.
Changes in sympathetic nerve activity of the mammalian ovary during a normal estrous cycle and in polycystic ovary syndrome: Studies on norepinephrine release
Authors: Lara H.E. , Dorfman M. , Venegas M. , Luza S.M. , Luna S.L. , Mayerhofer A. , Guimaraes M.A. , Rosa E Silva A.A.M. , Ramírez V.D.
Published: December 2002

Although it has been known for many years that the ovary is innervated by catecholaminergic nerve fibers and much experimental evidence has strengthened the notion that catecholamines are physiologically involved in the control of ovarian function, scarce evidence has been presented as to the role of sympathetic activity in ovarian pathologies that affect reproductive function. The purpose of this article is to provide a succinct overview of the findings in this area and discuss them relative to the pathology of polycystic ovary syndrome, the most common ovarian pathology in women during their reproductive years. Microsc. Res. Tech. 59:495–502, 2002. © 2002 Wiley‐Liss, Inc.
Preovulatory rise of NGF in ovine follicular fluid: Possible involvement in the control of oocyte maturation
Authors: Barboni Barbara , Mattioli Mauro , Gioia Luisa , Turriani Maura , Capacchietti Giulia , Berardinelli Paolo , Bernabò Nicola
Published: December 2002

Since nerve growth factor (NGF) is produced in vitro by granulosa cells after gonadotropin stimulation, the present research has been designed to investigate whether this neurotropin is involved in the events triggered by the gonadotropin surge that lead the follicle to ovulate a mature oocyte. To this aim, NGF levels in follicular fluid, collected before or 20 hours after the gonadotropin surge, was measured by ELISA. To evaluate whether NGF may have a non‐neurotropic effect on follicle cells, the presence of NGF receptors was investigated by immunohistochemistry and further evaluated by analysing the tyrosine‐phosphorylation pattern after NGF stimulation in vitro. The effect of NGF on the degree of cumulus expansion, cumulus‐oocyte metabolic coupling, and meiotic maturation was finally studied by using the culture of follicle‐enclosed oocyte. The results demonstrate that GnRH causes a dramatic rise of NGF in large follicles. Immunohistochemistry revealed a discrete positivity for trkA receptors localised in cumulus cells. Tyrosine phosphorylation pattern confirms that somatic cells are capable to transduce NGF signal. By contrast, all the oocytes examined were negative for trkA and did not change the phosphorylation pattern after NGF. In vitro NGF (100 ng/ml) induced a marked cumulus expansion and a progressive cumulus‐oocyte uncoupling similar to that produced by gonadotropins. The addition of NGF also caused the resumption of meiosis in more than 70% of the oocytes analysed with an effect that is only slightly less pronounced than that of gonadotropins (80%). The increase in NGF secretion following gonadotropin surge suggests that this neurotropin may be involved in the control of oocyte maturation. Microsc. Res. Tech. 59:516–521, 2002. © 2002 Wiley‐Liss, Inc.
Intrinsic neurons in the mammalian ovary
Authors: D'Albora Hortensia , Anesetti Gabriel , Lombide Paula , Dees W. Les , Ojeda Sergio R.
Published: December 2002

Mammalian ovarian function is under endocrine and neural control. Although the extrinsic innervation of the ovary has been implicated in the control of both ovarian development and mature function, it is now clear that, from rats to humans, the ovary is endowed with a network of intrinsic neurons displaying diverse chemical phenotypes. This article describes the presence of these intrinsic neurons in the ovary of different mammalian species, and discusses the possible functions that they may have in the regulation of ovarian physiology. Microsc. Res. Tech. 59:484–489, 2002. © 2002 Wiley‐Liss, Inc.
Role of the central and peripheral nervous system in the ovarian function
Authors: Aguado Luis I.
Published: December 2002

This review attempts to give a comprehensive overview of ovarian innervation, considering the whole nervous system and its different levels that may modify the ovarian function. The connection between the ovary and the central nervous system through the autonomic pathways, including the peripheral ganglia, is highlighted. The evidence obtained over the last years highlights the role of the superior ovarian nerve (SON) in the ovarian phenomena. Besides, the effect on the ovary of conventional neurotransmitters and others such as indolamines and peptides, which have been found in this organ, are discussed. Various reproductive diseases have been studied almost exclusively from the endocrine point of view. It is evident that a better knowledge about the role of the neural factors involved in the ovarian physiology may facilitate the understanding of some of these. A review of the concepts and an update of some experimental designs is made that permits clarifying several aspects of the relationship between the neural system and the ovary. At present, there is no doubt that the innervation of the ovary is involved in several physiological aspects of this gland function. However, the relationship of some levels of the nervous system and the ovary offer a wide avenue for future research. Microsc. Res. Tech. 59:462–473, 2002. © 2002 Wiley‐Liss, Inc.
System for combined three‐dimensional morphological and molecular analysis of thick tissue specimens
Authors: Fernandez‐Gonzalez Rodrigo , Jones Arthur , Garcia‐Rodriguez Enrique , Chen Ping Yuan , Idica Adam , Lockett Stephen J. , Barcellos‐Hoff Mary Helen , Ortiz‐De‐Solorzano Carlos
Published: December 2002

We present a new system for simultaneous morphological and molecular analysis of thick tissue samples. The system is composed of a computer‐assisted microscope and a JAVA‐based image display, analysis, and visualization program that allows acquisition, annotation, meaningful storage, three‐dimensional reconstruction, and analysis of structures of interest in thick sectioned tissue specimens. We describe the system in detail and illustrate its use by imaging, reconstructing, and analyzing two complete tissue blocks that were differently processed and stained. One block was obtained from a ductal carcinoma in situ (DCIS) lumpectomy specimen and stained alternatively with Hematoxilyn and Eosin (H&E), and with a counterstain and fluorescence in situ hybridization (FISH) to the ERB‐B2 gene. The second block contained a fully sectioned mammary gland of a mouse, stained for histology with H&E. We show how the system greatly reduces the amount of interaction required for the acquisition and analysis and is, therefore, suitable for studies that require morphologically driven, wide‐scale (e.g., whole gland) analysis of complex tissue samples or cultures. Microsc. Res. Tech. 59:522–530, 2002. Published 2002 Wiley‐Liss, Inc.
Determination of chloride efflux by X‐ray microanalysis versus MQAE‐fluorescence
Authors: Andersson Charlotte , Roomans Godfried M.
Published: December 2002

The importance of chloride channels for the cell is demonstrated by a number of serious human diseases that are due to mutations in chloride channels. The most well‐known of these diseases is cystic fibrosis. Investigations into the mechanisms of the disease and possible treatments require the study of chloride fluxes at the level of individual cells. The present study compares two methods for studies of chloride transport: X‐ray microanalysis and MQAE fluorescence with image analysis. As an experimental system, the cAMP‐activated chloride channel in cultured respiratory epithelial cells was chosen. Both methods showed that stimulation with the cAMP‐elevating agents forskolin and IBMX decreased the chloride content of the cells by about 20–27%. Inducing a driving force for chloride by replacing extracellular chloride by nitrate resulted in a chloride efflux that was significantly increased in the presence of forskolin and IBMX. This study shows that X‐ray microanalysis and MQAE fluorescence are adequate and comparable methods for measuring cAMP‐dependent chloride transport in individual cells. Microsc. Res. Tech. 59:531–535, 2002. © 2002 Wiley‐Liss, Inc.
Confocal laser scanning microscopy to study formation and properties of polyelectrolyte nanocapsules derived from CdCO3 templates
Authors: Silvano D. , Krol S. , Diaspro A. , Cavalleri O. , Gliozzi A.
Published: December 2002

Three‐dimensional confocal laser scanning microscopy (CLSM) was used as an essential investigation method to obtain information about the formation and morphological characteristics of nanocapsules. Nanocapsules are built by layer‐by‐layer deposition of alternatively charged polyelectrolytes on templates forming nanostructured hollow shells. CLSM is unique in allowing for monitoring of the core dissolution process in real time and for studying nanocapsule functioning in hydrated conditions within a three‐dimensional and temporal framework. Since we are also interested in the identification of other possible templates, we briefly report on the use of yeast cells as biocolloidal cores monitored by means of two‐photon microscopy. Here we focus our attention on the use of CdCO3 crystals as template candidates for the preparation of stable capsules. Both cubic and spherical CdCO3 cores have been produced. Cubic cores exhibit higher monodispersity and smaller size compared to spherical ones. Capsules templated on these cores have a higher surface‐to‐volume ratio that is valuable for applications related to drug delivery, functional properties of the shells and adsorption of proteins, and other biologically relevant molecules. Microsc. Res. Tech. 59:536–541, 2002. © 2002 Wiley‐Liss, Inc.