Search PubMed⌕ Search

Biomedical subjects

M Germain

Publications and source records attributed to M Germain.

At least 55 records · Page 3Linked to original sources
PubMed2000

Smoldering HTLV-1-induced T-cell lymphoma localized within the skin; a radiation-resistant tumor.

BACKGROUND: Human T-cell lymphotrophic virus type 1 (HTLV-1)-induced lymphoproliferative disease occurs in approximately 3-5% of people in endemic areas who have been HTLV-1 positive for decades. Lymphoproliferative disease may present as four subtypes, including an acute adult T-cell leukemia/lymphoma (ATLL), an aggressive HTLV-1 lymphoma, chronic ATLL, and smoldering ATLL. MATERIALS AND METHODS: A 72-year-old HTLV-1+ Haitian woman presented with a 2-year history of a cutaneous eruption localized to the right arm. The eruption had evolved into multinodular lesions over the past 6-7 months. Peripheral blood and cutaneous biopsy specimens were evaluated. Immunohistochemical studies for lymphoid markers were performed on the cutaneous biopsy material, and polymerase chain reaction (PCR) and Southern blot assay were evaluated for the presence and integration of HTLV-1 within the genome. RESULTS: The biopsy specimen showed a pleomorphic T-cell infiltrate with epidermotrophism, and an immunohistochemical phenotype showing CD3+, CD4+, CD8-, CD25, CD30-, HLDA-DR+ cells. PCR and Southern blot assay evaluation showed a single clonal integration of HTLV-1 provirus within a monoclonal tumor cell population. The patient had no abnormal lymphoid forms on peripheral smear at presentation, and no evidence of other organ involvement. CONCLUSIONS: Smoldering HTLV-1-induced lymphoma is uncommon even in endemic areas. In previously reported cases, the smoldering variant was accompanied by abnormal forms in the peripheral blood and/or by other signs of systemic disease. This case illustrates that smoldering disease may be localized to the skin with no detected morphologic abnormalities on peripheral smear.

Aged↗
PubMed2000

Dialysis discontinuation and palliative care.

Little attention has been accorded to the terminal course and end-of-life care of patients after dialysis discontinuation. This prospective cohort observational study involves six dialysis clinics in the United States and two clinics in Canada. Data were collected on 131 patients who were undergoing maintenance dialysis and died after treatment discontinuation. Seventy-nine of the patients (60%) were prospectively studied until their deaths. Caregivers and families provided information about the symptoms and treatment provided in the final 24 hours of life, and structured interviews were conducted at the time of stopping dialysis with patients and families. The patient population was primarily white (73%), elderly (70 +/- 1.2 years), and diabetic (46%). Three quarters of the subjects had between three and seven comorbid conditions. Pain and agitation were the most common symptoms during the last day of life. Terminal treatment was generally considered to be satisfactory, and most people had good deaths. Although dialysis prolongs life, the integration of palliative medicine into dialysis programs offers opportunities to improve the quality of end-of-life care, especially for those patients who elect to stop treatment. Recommendations include making advance care planning an expectation at all clinics and using quality-of-dying measures to establish benchmarks for the provision of terminal care.

Adolescent↗
PubMed2000

Food intake regulation in rodents: Y5 or Y1 NPY receptors or both?

Neuropeptide Y (NPY), one of the most abundant peptides in rat and human brains, appears to act in the hypothalamus to stimulate feeding. It was first suggested that the NPY Y1 receptor (Y1R) was involved in feeding stimulated by NPY. More recently a novel NPY receptor subtype (Y5R) was identified in rat and human as the NPY feeding receptor subtype. There is, however, no absolute consensus since selective Y1R antagonists also antagonize NPY-induced hyperphagia. Nevertheless, new anti-obesity drugs may emerge from further pharmacological characterization of the NPY receptors and their antagonists. A large panel of Y1R and Y5R antagonists (such as CGP71683A, BIBO3304, BIBP3226, 1229U91, and SYNAPTIC and BANYU derivatives but also patentable in-house-synthesized compounds) have been evaluated through in vitro and in vivo tests in an attempt to establish a predictive relationship between the binding selectivity for human receptors, the potency in isolated organs assays, and the inhibitory effect on food intake in both normal and obese hyperphagic rodents. Although these results do not allow one to conclude on the implication of a single receptor subtype at the molecular level, this approach is crucial for the design of novel NPY receptor antagonists with potential use as anti-obesity drugs and for evaluation of their possible adverse peripheral side effects, such as hypotension.

Animals↗
PubMed1999

Cleavage of automodified poly(ADP-ribose) polymerase during apoptosis. Evidence for involvement of caspase-7.

The abundant nuclear enzyme poly(ADP-ribose) polymerase (PARP) synthesizes poly(ADP-ribose) in response to DNA strand breaks. During almost all forms of apoptosis, PARP is cleaved by caspases, suggesting the crucial role of its inactivation. A few studies have also reported a stimulation of PARP during apoptosis. However, the role of PARP stimulation and cleavage during this cell death process remains poorly understood. Here, we measured the stimulation of endogenous poly(ADP-ribose) synthesis during VP-16-induced apoptosis in HL60 cells and found that PARP was cleaved by caspases at the time of its poly(ADP-ribosyl)ation. In vitro experiments showed that PARP cleavage by caspase-7, but not by caspase-3, was stimulated by its automodification by long and branched poly(ADP-ribose). Consistently, caspase-7 exhibited an affinity for poly(ADP-ribose), whereas caspase-3 did not. In addition, caspase-7 was activated and accumulated in the nucleus of HL60 cells in response to the VP-16 treatment. Furthermore, caspase-7 activation was concommitant with PARP cleavage in the caspase-3-deficient cell line MCF-7 in response to staurosporine treatment. These results strongly suggest that, in vivo, it is caspase-7 that is responsible for PARP cleavage and that poly(ADP-ribosyl)ation of PARP accelerates its proteolysis. Cleavage of the active form of caspase substrates could be a general feature of the apoptotic process, ensuring the rapid inactivation of stress signaling proteins.

Apoptosis↗
PubMed1999

Immunological determination and size characterization of poly(ADP-ribose) synthesized in vitro and in vivo.

Poly(ADP-ribose) polymerase is a DNA break detecting enzyme playing a role in the surveillance of genome integrity. Poly(ADP-ribose) is synthesized rapidly and transiently from beta-NAD in response to DNA damaging agents. In order to study the physiological significance of poly(ADP-ribose) metabolism, we have developed immunological methods which enable us to study endogenous poly(ADP-ribose) without interfering with cell metabolism and integrity. For this purpose, we produced a highly specific polyclonal anti-poly(ADP-ribose) antibody which immunoreacts with polymers and oligomers. In addition to the immunodot blot method recently described by us (Affar et al., Anal. Biochem. 259 (1998) 280-283), other applications were investigated in cells: (i) detection of poly(ADP-ribose) by ELISA; (ii) characterization of poly(ADP-ribose) size using high resolution gel electrophoresis of polymers, followed by its transfer onto a positively charged membrane and detection with anti-poly(ADP-ribose) antibody; (iii) immunocytochemistry and flow cytometry analyses allowing poly(ADP-ribose) study at the level of individual cells.

Animals↗
PubMed1999

Long-term maintenance of therapeutic cyclosporine levels leads to optimal graft survival without evidence of chronic nephrotoxicity.

Since the introduction of cyclosporine into clinical use, a major area of concern within the transplant community has been the fear of chronic nephrotoxicity. Although progressive renal damage does appear to occur in native kidneys of heart and liver transplant patients receiving cyclosporine, it has been our contention that its use is not a major cause of deterioration in renal allografts. We therefore undertook a study of 91 consecutive renal transplants performed over a three-year period with a minimum graft survival of 1 year and a follow-up of 7-9 years. Serial serum creatinine values, iothalamate clearances and cyclosporine levels were obtained at 3 months after transplantation and yearly thereafter. Biopsies were performed on all grafts that had failed as well as on the majority of patients with deteriorating renal function, and were interpreted by two nephropathologists. As measured by iothalamate clearances, 65% of the patients in this series exhibited absolutely stable renal function despite the maintenance of cyclosporine levels of more than 200 ng/ml for 7-9 years. Since these stable patients did not reveal any decline in renal function, it therefore follows that they did not experience chronic cyclosporine nephrotoxicity. Furthermore, none of the patients with declining renal function or with failed grafts showed any evidence of nephrotoxicity on biopsy. Chronic cyclosporine nephrotoxicity may be a cause of declining function or graft loss with renal transplant recipients, but if so, it is exceedingly rare.

Creatine↗
PubMed1999

Increased soft tissue in the posterior cervical and upper back area of patients on HIV-1 protease inhibitors.

BACKGROUND: Corticosteroids as well as sex hormones affect the redistribution of subcutaneous fat and the percentage of lean body mass. In addition, some stromal cells express steroid receptors, and the quantity and distribution of these receptors vary at different body sites and between sexes. Inhibitors of HIV-1 protease may affect steroid hormone metabolism through their effect on cytochrome P450. OBJECTIVES: To determine the changes in the tissue of the back in three HIV-1+ patients who developed increased soft tissue in posterior cervical and upper back areas while on HIV-1 protease inhibitors. METHODS: Punch biopsies of the involved posterior cervical and upper back areas were done. These included subcutaneous adipose tissue. Routine hematoxylin and eosin-stained sections, along with special stains for elastic and stromal mucin, and immunohistochemical stains for CD34 (HPCA-1 and Factor XIIIa) were evaluated. RESULTS: Histologically all three patients showed identical features. There was expansion of the dermis with decreased periadnexal fat and marked widening of the fibrous septa within the expanded subcutaneous fat. CONCLUSIONS: The posterior cervical and upper back area appears to be a common site for localization of mesenchymal tumours that show some fat differentiation and produce an increase in stromal matrix material. Mesenchymal cell populations within this area are also affected by systemic diseases. A male predominance pattern occurs with these conditions, and steroid receptors are expressed on some mesenchymal cells, that vary with the body location. Thus, this observation may be related to the effects of protease inhibitors on steroid hormone metabolism through their inhibition of cytochrome P-450.

Adipose Tissue↗
PubMed1999

Musculocutaneous flap of the transverse nasalis muscle in repair of nasal-tip skin carcinoma.

OBJECTIVE: Reconstructing a nasal tip when there is neoplastic involvement is difficult, owing to the nature of the skin, which is thick, adhesive, and not very flexible, and to the proximity of the lower rim of the nasa ala, which must be respected. Dissection of twenty injected anatomic preparations has shown the reliability of using the vascular pedicle of the musculocutaneous flap of the transverse nasalis muscle. The technique was used in ten patients with skin carcinoma of the nasal tip. Esthetic results are excellent since the nasal ala is respected. A double-flap procedure may also be used for median defects.

Aged↗
PubMed1998

NPY receptor subtypes involved in the contraction of the proximal colon of the rat.

Experiments were designed to determine the receptor subtype(s) involved in the contraction of the rat proximal colon to NPY. In this tissue, mRNA of Y2 and Y4 NPY receptor subtypes were highly expressed, whereas Y5 mRNA levels were very low and Y1 mRNA levels were intermediate. NPY analogues induced contractions with the following order of potency: rPP > hPP = PYY = NPY = [Leu31,Pro34]NPY > NPY(2-36) = [D-Trp32]NPY > NPY(33-36). Responses to NPY, PYY and NPY(13-36) were not or partially affected by tetrodotoxin, in contrast to the responses to [Leu31,Pro34]NPY, rPP, hPP and [D-Trp32]NPY which were fully blocked. Atropine did not inhibit the contractions to NPY, PYY and [Leu31,Pro34]NPY but significantly affected those to NPY(13-36), [D-Trp32]NPY, rPP and hPP. The specific Y1 receptor antagonist BIBP 3226 was ineffective but JCF 104 and JCF 105 (two compounds with preferential affinity toward the hY5 receptor versus the hY1 or hY2 receptor) abolished the contractions provoked by the NPY analogues. These results suggest that NPY activates three receptor subtypes, a Y2 subtype possibly by a direct action on the smooth muscle cells, as well as a Y4 and a Y5 (or 'Y5-like') subtype which, respectively, release acetylcholine and an unknown neurotransmitter.

Animals↗
PubMed1998

Prior pregnancy outcome and the risk of intraamniotic infection in the following pregnancy.

OBJECTIVE: Our purpose was to determine whether the outcome of a prior pregnancy influenced the risk of intraamniotic infection in the following pregnancy. STUDY DESIGN: A case-control study was conducted at five King County, Washington, hospitals from 1990 through 1994. Cases (n = 585) of intraamniotic infection were identified by a medical record review for clinical signs of infection during labor and compared with controls (n = 575). Women were classified as having a spontaneous abortion or elective termination if the pregnancy had been diagnosed by a health care professional before 20 weeks and was verified by medical record review. Adjusted odds ratios and 95% confidence intervals were estimated using logistic regression. RESULTS: Women with spontaneous abortion (odds ratio = 4.3; 95% confidence interval 2.9 to 6.4) or elective termination (odds ratio = 4.0; 95% confidence interval 2.7 to 5.8) had an increased risk of intraamniotic infection. The increased risk was similar for women who did and did not have an earlier pregnancy carried beyond 20 weeks. CONCLUSIONS: Women who have had a spontaneous abortion or an elective termination have an increased risk of intraamniotic infection regardless of previous successful pregnancy outcome.

Abortion, Induced↗
PubMed1998

Evaluation of clinical algorithms for the diagnosis of gonococcal and chlamydial infections among men with urethral discharge or dysuria and women with vaginal discharge in Benin.

OBJECTIVE: To evaluate the validity of clinical algorithms proposed in Benin for the diagnosis of gonococcal or chlamydial infections among men with urethral discharge or dysuria and women with vaginal discharge consulting health services in Benin. These algorithms were adapted from those proposed by the World Health Organisation. METHODS: Consecutive patients with these symptoms were enrolled at three primary healthcare centres. The reference test for gonorrhoea was a combination of results from culture and polymerase chain reaction and chlamydial infection was ascertained by enzyme linked immunosorbent assay and PCR. In women, two algorithms were evaluated, one based on symptoms and risk assessment (algorithm A), the other relying also on speculum examination (algorithm B). The first algorithm evaluated in men relied on clinical examination only (algorithm C) whereas the other used microscopic examination of urethral smears (algorithm D). Sensitivity, specificity, and positive and negative predictive values of these algorithms were assessed using standard methods. RESULTS: In 192 women, the prevalence of gonococcal and chlamydial infections was 5.7% and 2.1% respectively (combined prevalence of 7.8%). The sensitivity, specificity, positive and negative predictive values of algorithm A (algorithm B) were respectively 86.7% (93.3%), 41.8% (34.5%), 11.2% (10.8%), and 97.4% (98.4%). In 105 men, the corresponding prevalences were 39.0% and 7.6% respectively (for a combined prevalence of 44.8%). The sensitivity, specificity, positive and negative predictive values of algorithm C (algorithm D) were respectively 91.5% (87.2%), 60.3% (67.2%), 65.2% (68.3%), and 89.7% (86.7%). CONCLUSION: A syndromic approach for the diagnosis of urethritis in men appears appropriate. In women, the diagnosis of gonococcal or chlamydial infection without specific laboratory tests, which are not easily affordable in developing countries, remains highly problematic.

Adult↗
PubMed1998

Proteolysis of poly(ADP-ribose) polymerase by caspase 3: kinetics of cleavage of mono(ADP-ribosyl)ated and DNA-bound substrates.

Poly(ADP-ribose) polymerase (PARP) is an abundant nuclear enzyme which is responsible for synthesis of poly(ADP-ribose) in response to DNA damage caused by numerous agents and during DNA base excision repair. After DNA damage, the enzyme binds to nicks in DNA through its N-terminal zinc fingers and catalyzes the formation of poly(ADP-ribose) on various nuclear acceptors including itself. When DNA damage is extensive, cells induce their own demise by activating the proteases that induce apoptosis (caspases) which cleave PARP and other death substrates. Here we report the development of a new approach to investigate the sensitivity of mono(ADP-ribosyl)ated and DNA-bound PARP to cleavage during apoptosis. The development of a stoichiometric labeling procedure of the enzyme has allowed us to evaluate the catalytic properties of caspase 3 toward mono(ADP-ribosyl)ated PARP at various enzyme:substrate molar ratios. We show that low levels of automodification (< or = 3 U of ADP-ribose per chain) do not inhibit the proteolysis of the substrate. In addition, we demonstrate that binding of unmodified PARP to DNA influences the kinetics of its cleavage by caspase 3.

ADP Ribose Transferases↗
PubMed1997

Evaluation of a screening algorithm for the diagnosis of genital infections with Neisseria gonorrhoeae and Chlamydia trachomatis among female sexworkers in Bénin.

BACKGROUND AND OBJECTIVES: In developing countries, simple and cheap procedures for the diagnosis of sexually transmitted diseases (STDs) are urgently needed, especially for screening purposes in high risk groups. GOALS: To evaluate the sensitivity and specificity of a screening algorithm for STDs among 364 female sex workers in Bénin, in comparison with reference laboratory tests. STUDY DESIGN: The algorithm relied on the following criteria, which were evaluated in sequence: the presence of endocervical mucopus on visual inspection of the cervix, a positive swab test, or a microscopic examination of vaginal fluid showing more than 10 polymorphonuclear cells per field. The algorithm diagnosed an infection if any one of these criteria was fulfilled. True infectious status was determined by the combined results of culture for Neisseria gonorrhoeae, enzyme immunoassay for Chlamydia trachomatis, and polymerase chain reaction assays for both infections. RESULTS: Gonococcal or chlamydial infection was diagnosed in 39.8% of the study population according to the reference tests. The algorithm had a sensitivity of 57.9% and a specificity of 61.2%. In the presence of Candida sp or Trichomonas vaginalis, specificity decreased to 39.1%, but sensitivity increased to 67.5%. CONCLUSIONS: These results underscore the limitations of simple, nonlaboratory diagnostic tools for screening STDs in high-risk groups in developing countries. Further research is needed to increase the validity--especially the sensitivity--of these algorithms.

Algorithms↗
PubMed1997

Early effects of ganciclovir therapy on the quantity of cytomegalovirus DNA in leukocytes of immunocompromised patients.

The cytomegalovirus (CMV) DNA load in leukocytes was measured in 26 immunocompromised patients with CMV disease before and after 10 days of intravenous ganciclovir therapy. Before therapy, the circulating DNA burden of bone marrow transplant recipients was significantly lower than that of other transplant or AIDS patients. Ganciclovir induction therapy significantly decreased the viral DNA load in the leukocyte populations of most patients.

Acquired Immunodeficiency Syndrome↗
PubMed1997

[Free fibula transplant and practical approach in the absence of posterior tibial artery. A report of 2 cases].

The authors report two well documented cases of absent posterior tibial artery in patients undergoing free fibula transplant. The first patient was a 50-year-old woman treated by pelvimandibulectomy for squamous cell carcinoma, leaving a defect of the floor of the mouth. The second case was an 11-year-old child with Ewing sarcoma of the femoral metaphysis, in whom femoral reconstruction was performed by vascularized free fibula transplant. Based on these two cases, the authors describe their diagnostic and therapeutic approach designed to avoid risks associated with this anatomical variant. Absence of the posterior tibial artery can be confirmed by arteriography and duplex ultrasound. The authors propose duplex ultrasound as first-line investigation as this safe, noninvasive examination provides sufficient information in the majority of cases at a lower cost. In parallel, the various anatomical variants affecting the origin of leg arteries from the popliteal artery are classified into seven groups based on a phylogenetic and embryological study.

Bone Neoplasms↗
PubMed1996

Water balance during and after marathon running.

To describe the time course of plasma volume alterations and the changes in the plasma concentrations of hormones regulating water balance in relation to a marathon race, six experienced marathon runners (five men, one women) aged 28 (SD 6) years were studied during and for the 3 days following a treadmill marathon run at 68 (SD 5) percent of maximal oxygen consumption. Haematocrit, haemoglobin, plasma protein (Prot) and electrolyte (Na+, K+) concentration, osmolality (osm), plasma concentrations of renin (Ren), aldosterone (Ald) and atrial natriuretic peptide (ANP) were determined at rest in a sitting position (T(-30)), and then after 30 min in an upright posture (R(0)), while running a marathon at 10 km (R(10)), 30 km (R(30)) and 42.2 km (R end), and after the marathon at 30 min (T(30)), 60 min (T(60)), 120 min (T(120)) and 24 h (TD(+1)), 48 h (TD(+2)) and 72 h (TD(+3)). The changes in plasma volume (PV), Prot, osm and Na+ observed during the race were nonsignificant. Significant increases in plasma concentration of K+ [4.8 (SD 0.6) vs 5.5 (SD 0.6) mmol*1(-1); P <0.01], Ren [38(SD 57) vs 197 (SD 145) pmol*1(-1); P <0.02] and Ald [175 (SD 142) vs 1632 (SD 490) pmol*1(-1); P <0.01] were observed at R(end). A significant increase of ANP (P <0.05) was only found after R(10). Body mass significantly decreased by 2.0 kg (P <0.01) during the race in spite of the ingestion of 1.46 (SD 0.34)1 of a 5 percent glucose solution. Urinary volume and Na+ excretion dropped significantly after the completion of the marathon in comparison with the day before [2600 vs 1452 ml*day(-1)(P <0.02) and 161.3 vs 97.1 mmol*1(-1) (P <0.05)]. At TD(+1) and TD(+2) a significant increase in PV was noted, compared to T(-30). The lack of a decrease in PV during the marathon may have been due to the production of 402 g of metabolic water and by the release of 1280 g of water stored in glycogen complexes in muscle and liver. Thus, the hormone response during the marathon may have been due to the effects of the exercise itself and not to the effects of dehydration. The postmarathon PV expansion may be explained by a protein shift to the intravascular space and by renal sodium retention.

Adult↗