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Biomedical subjects

M Reiss

Publications and source records attributed to M Reiss.

At least 163 records · Page 9Linked to original sources
PubMed1996

[Is there a pathological basis for lefthandedness?].

The determination of laterality or handedness in men is a multifactorial one. There is a strong evidence for a genetic component in handedness, but there is only some evidence for other components. The present review discusses the role of the pathological factors, especially birth stress, birth order, maternal age or laterality in clinical populations. There is a general agreement that sinistrality can occur as a result of pre- or perinatal damage to the left hemisphere. The review indicates that there is no sure evidence to suggest that birth stress or birth order are related to increases in non-rightsidedness. A disproportionate number of sinistrals is found in clinical populations. The present review discusses some possible hypothesis explaining the distribution of sinistrality.

Birth Order↗
PubMed1996

Trifluoperazine as a modulator of multidrug resistance in refractory breast cancer.

Overexpression of P-glycoprotein (P-gp) has been implicated as the mechanism of multidrug resistance (MDR) in a number of human cancers, including carcinoma of the breast. We conducted a clinical trial to determine whether the P-gp inhibitor, trifluoperazine, could sensitize patients with refractory breast cancer to vinblastine chemotherapy. Adult patients with histologically confirmed, refractory, advanced breast cancer were treated with vinblastine at a dose of 1.7 mg/m2 per day by continuous infusion for five consecutive days. Patients who did not respond after two cycles were subsequently treated with vinblastine plus trifluoperazine at a dose of 8 mg twice daily during the five days of chemotherapy. In patients from whom tumor samples were available, the expression of P-gp was determined by immunocytochemistry. Of 35 patients enrolled, 30 were evaluable, 2 of whom (7%) achieved a partial response to vinblastine alone. Among the 16 patients treated with vinblastine plus trifluoperazine there was one response (6%) which lasted 16 weeks. Tumor samples were available from 16 patients, and 14 (87%) were immunoreactive for P-pg. P_pg expression was detected both in the patient who responded to vinblastine plus trifluoperazine and in one of the two patients who responded to vinblastine alone. Continuous-infusion vinblastine demonstrated limited activity in this study. Furthermore, trifluoperazine did not effectively reverse established resistance to vinblastine. This failure may be related the presence of multiple mechanisms of drug resistance in the heavily pretreated population, or because ineffective concentrations of the modulator were achieved in vivo. Future studies should evaluate more effective modulators, and attempt to reverse MDR earlier in the course of treatment, before other forms of resistance can develop.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1996

[Diagnostic and therapeutic problems in gunshot wounds].

BACKGROUND: Bullet wounds are a rare occurrence during times of peace. Recently, however, there has been a general increase in the relative number and severity of this type of trauma. In times of peace, gunshot wounds may be mainly caused by suicide attempts, negligent handling of firearms and especially violent conflicts. Bullet wounds, in contrast to wounds caused by a blow or impact to the viscerocranium, are characterised by an irregular path, entry and exit wounds, as well as localised demolition of bones with the associated defects. PATIENTS: 30 patients with gunshot wounds were treated during the past 35 years. Basing on four case reports, problems of interdisciplinary treatment approach to gunshot wounds are discussed, as well as the diagnostic and therapeutic consequences. RESULTS AND CONCLUSIONS: The first case concerns a retained missile in the left fossa pterygopalatina. Intraoperative removal caused a rupture of the A. maxillaris. Preoperative angiography could have provided valuable information. In the second case, an injury caused by a shot from a blank cartridge pistol in the left facial area resulted in extensive wounds with several surgical revisions. The third case was a shot injury to the tongue with an unexpected wound and bleeding. The fourth case describes a child with a bullet in a hyperplastic adenoid tonsil. Primary careful treatment is of greatest significance for functional and cosmetic results due to extensive rupturing and wounds.

Adolescent↗
PubMed1996

Ipsilateral breast tumor recurrence as a predictor of distant disease: implications for systemic therapy at the time of local relapse.

PURPOSE: To evaluate the prognostic significance of ipsilateral breast tumor recurrence (IBTR) with respect to the subsequent development of distant metastasis. MATERIALS AND METHODS: Between January 1970 and December 1989, 973 patients with invasive breast cancer were treated with conservative surgery and radiation therapy at Yale-New Haven Hospital. The median follow-up time as of December 1993 was 8.6 years. A number of prognostic factors were tested as possible predictors of distant metastases, including whether a patient experienced IBTR. IBTRs were broken down by time to recurrence to determine whether the breast recurrence-free interval had any prognostic relevance with respect to the development of distant metastasis. RESULTS: As of December 1993, out of the entire population of 973 patients, 73 patients had developed IBTR and 134 had developed distant metastases. The overall actuarial survival rate at 10 years was .71 +/- .02, with a 10-year actuarial breast recurrence-free rate of .84 +/- .02 and a 10-year distant metastasis-free rate of .77 +/- .02. The overall distant metastasis rate was higher in patients who experienced IBTR compared with patients who had never experienced IBTR. Furthermore, the time to IBTR had a significant effect on distant metastases. Of 32 patients who developed an IBTR within 4 years of original diagnosis, 16 (50%) developed distant metastases. In contrast, of 41 patients who developed later breast relapses (> 4 years from original diagnosis), only seven (17%) developed distant metastases (P < .01). Of 32 patients who developed early breast relapse, the 5-year survival rate following breast relapse was .50 +/- .01, compared with a 5-year post-breast relapse survival rate of .78 +/- .10 among 41 patients with later breast relapses (P < .05). CONCLUSION: It appears that early IBTR is a significant predictor for distant metastases. Whether early breast tumor relapse is a marker for or cause of distant metastases remains a controversial and unresolved issue. Implications for adjuvant systemic therapy at the time of breast relapse are discussed.

Adult↗
PubMed1996

Interferon-inducible protein-10 and the pathogenesis of cutaneous T-cell lymphomas.

Human interferon-g inducible protein-10 (IP-10), a small basic protein secreted by interferon (INF)-g stimulated keratinocytes, is chemotactic for normal CD4-positive lymphocytes and inhibits early normal and leukemic hemopoietic progenitor proliferation. Cutaneous T-cell lymphoma (CTCL) is an indolent CD4-positive lymphoma characterized by multiple skin relapses before visceral dissemination. We investigated the role of IP-10 in the biology of CTCL by using immunocytochemistry to define IP-10 expression in normal and CTCL skin biopsies. Using purified recombinant (r) IP-10, we generated a rabbit antiserum that recognized and neutralized rIP-10 but did not cross-react with any keratinocyte proteins or any other chemokine. Immunoperoxidase staining of normal epidermis demonstrated that IP-10 was expressed by basal but not by differentiated keratinocytes. The epidermis overlying CTCL lesions was often hyperplastic, IP-10 immunostaining was enhanced compared to normal skin, and extended to the suprabasal keratinocytes in 25 of 26 patients for a frequency of 96%; and 95% confidence interval (CI) of 80% to 100%. However, IP-10 was detectable in the dermal or epidermal lymphoid infiltrates in only three of these 26 patients (12%; 95% Cl, 2% to 39%). Skin clinically free of CTCL demonstrated normal IP-10 immunostaining. In one patient who had matching biopsies performed before and after treatment, IP-10 was initially overexpressed before treatment but was normally expressed when he achieved remission. These results suggest that IP-10 may play a role in the epidermotropism of CTCL. More work is required to determine whether IP-10 stimulates or inhibits CTCL proliferation. A better understanding of the growth controls operating in CTCL may be used to develop curative therapies for this disorder.

Adult↗
PubMed1996

Loss of transforming growth factor-beta type II receptor gene expression in primary human esophageal cancer.

Cell lines derived from carcinomas of the upper aero-digestive tract are typically refractory to transforming growth factor beta-mediated cell cycle arrest. Recently, we reported that the type II transforming growth factor beta receptor (T beta R-II) gene can be inactivated on the basis of missense mutations in such cell lines. These findings prompted us to investigate the molecular status of the T beta R-II gene in primary tumor specimens. Among 21 of 24 evaluable primary esophageal carcinomas, there were 6 cases (28.5%; 95% confidence interval, 11% to 52%) in which T beta R-II transcripts were low or undetectable by a reverse transcription PCR assay. In one of these cases, we were able to ascribe the loss of T beta R-II gene expression to high-density methylation of promoter sequences. We failed to detect any mutations within the open reading frame of the remaining tumors that expressed T beta R-II mRNA. In this relatively small series of cases, loss of T beta R-II expression was independent of pathologic tumor stage, histologic subtype, or outcome of patients with esophageal cancer. Thus, loss of expression of the T beta R-II gene appears to be the predominant mechanism through which this gene is inactivated in esophageal cancer.

Base Sequence↗
PubMed1996

Alterations of transforming growth factor-beta 1 receptor type II occur in ulcerative colitis-associated carcinomas, sporadic colorectal neoplasms, and esophageal carcinomas, but not in gastric neoplasms.

BACKGROUND & AIMS: Gastric cancers, sporadic colorectal cancers, and ulcerative colitis (UC)-associated colorectal carcinomas and dysplasias manifest microsatellite instability (MI); however, esophageal carcinomas rarely exhibit MI. Recently, a transforming growth factor-beta 1 type II receptor (TGF-beta 1RII) mutation in a coding microsatellite was described in primary colorectal carcinomas demonstrating MI. No previous studies of TGF-beta 1RII have addressed mechanisms of inactivation other than MI in human tumors; furthermore, MI-negative tumors have not been examined for TGF-beta 1RII mutation. We evaluated 138 primary human neoplasms for mutation in the poly-A microsatellite tract of TGF-beta 1RII. Additionally, a group of esophageal tumors was evaluated for the expression of TGF-beta 1RII messenger RNA (mRNA). METHODS: First, we determined whether MI was present at other chromosomal loci in these lesions. The poly-deoxyadenine (poly-A) microsatellite tract within the TGF-beta 1RII coding region was then PCR-amplified. In a group of MI-negative esophageal tumors, RT-PCR was performed to determine the expression of TGF-beta 1RII mRNA. RESULTS: Among 17 MI+ UC specimens, 3 (18%) demonstrated TGF-beta 1RII poly-A tract mutation (2 cancers and 1 dysplasia), while 2 (4%) of 44 MI-negative UC specimens (1 dysplasia and 1 tumor), and 13 (81%) of 16 MI+ sporadic colorectal cancers, contained TGF-beta 1RII poly-A mutation. No gastric or esophageal tumors contained TGF-beta 1RII mutation. Among 21 MI-negative esophageal carcinomas. 6 cases (28.5%) had TGF-beta 1RII transcripts that were low or undetectable by RT-PCR. CONCLUSIONS: Mutation within the poly-A microsatellite tract of TGF-beta 1RII occurs early in a subset of UC-neoplasms and commonly in sporadic colorectal cancers, but may be rare in MI+ gastric tumors. Diminished expression of TGF-beta 1RII mRNA in esophageal tumors suggests that mechanisms of inactivation in this gene other than MI play a role in esophageal carcinogenesis.

Colitis, Ulcerative↗
PubMed1996

[Laterality in twins].

The literature on twins and laterality is reviewed: Both monozygotic (MZ) and dizygotic twins (DZ) show a low concordance in all functional and morphological asymmetries. The proportions of R-R, R-L and L-L pairs in MZ twins and in DZ twins are in binomial distribution. The incidence of left-handedness is the same in MZ twins and DZ twins, but higher than in singletons. Other laterality signs do not show this tendency. The whole issue of twinning is as yet unresolved, yet it is clear already that no simple genetic model for the inheritance can be applied. The present review discusses three genetic models and associated problems with each. The overall tendency to a higher rate of left-handedness in twins could be due to such pathological factors (associated with twinning) as intrauterine crowding and perinatal stress, but is not due to so-called "mirror imaging"-phenomena in twins.

Functional Laterality↗
PubMed1995

Cloning of putative growth regulatory genes from primary human keratinocytes by subtractive hybridization.

In order to isolate genes that might be involved in regulating human keratinocyte (HKc) growth and/or differentiation, we constructed a cDNA library by subtractive hybridization between primary HKc and FaDu head-and-neck squamous cell carcinoma cells. Among the first set of independent cDNAs that we have isolated, ten correspond to known genes, and two represent novel sequences. Nine of the ten known genes are expressed at significantly lower levels in the majority of the SqCC cell lines in comparison with primary HKc. These include cDNAs that encode keratins K5 and K14 which are cytoskeletal proteins normally expressed in lining epithelia, the 14-3-3 protein stratifin/HME-1, lipocortin-II and CaN19 which are calcium-binding proteins that may play a role in HKc differentiation by regulating protein kinase C, plasminogen-activator inhibitor-2 which is a serine-proteinase inhibitor, HBp17 which is a HKc-specific secreted inhibitor of fibroblast growth factors, integrin alpha 3 which plays a role in the anchoring of keratinocytes to basement membrane, and YL-8, a ras-like protein that probably mediates intracellular protein trafficking. In addition, we isolated two cDNAs, LIS-1 which encodes the 45-kDa intracellular subunit of the platelet-activating factor acetyl-hydrolase, and the unknown sequence HFBCB84 which showed reduced expression in only a small number of tumor lines as compared to HKc. Inactivation or loss of any of these proteins may confer a selective advantage onto squamous epithelial cells and contribute to their malignant transformation.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMed1995

Missense mutations of the transforming growth factor beta type II receptor in human head and neck squamous carcinoma cells.

In this study, we report the occurrence of missense mutations of the transforming growth factor beta (TGF beta) type II receptor gene in two human squamous head and neck carcinoma cell lines. Both mutations are G:C-->C:G transversions, which result in the replacement of a glutamic acid by a glutamine, and of an arginine by a proline residue, respectively. Moreover, both are located at highly conserved sites within the serine-threonine kinase domain. One of the mutants appears to be defective in its autophosphorylation as well as in the transphosphorylation of the TGF beta type 1 receptor protein, whereas the second mutant appears to be constitutively activated. These are the first reported naturally occurring nucleotide substitution mutations in the T beta R-11 gene in human head and neck cancer cells, which may explain their resistance to TGF beta 1-mediated cell cycle arrest.

Amino Acid Sequence↗
PubMed1995

A study of leg-crossing in a German sample.

When a person is asked to cross their flexed legs then one thigh crossed over the other. This paper reviews the previous literature on leg crossing, and reports new data. In this study about 62% of the population (n = 292) are right leg-crossers, 26% are left leg-crossers, and the remaining 12% report that they have no preference or are indifferent. The incidence of left leg-crossing differs between the sexes, being higher in males, although there seems to be no association with age. Leg-crossing is correlated to some extent with footedness, handedness and eyedness.

Adult↗
PubMed1994

Functional evidence for an extracellular calcium receptor mechanism triggering tyrosine kinase activation associated with mouse keratinocyte differentiation.

Calcium-induced keratinocyte differentiation is associated with tyrosine phosphorylation of a p62 protein which associates with the ras-GTPase activating protein (GAP). We have examined the nature of the calcium signal triggering p62 phosphorylation. EGTA, a specific chelator of calcium, was able to completely block calcium-induced p62 phosphorylation, even after using conditioned medium from calcium-treated keratinocytes. Preventing calcium-induced cell-cell contacts by anti-cadherin antibodies did not inhibit tyrosine phosphorylation. Slight increases in extracellular calcium concentrations (0.15 or 0.30 mM) were already sufficient to induce p62 phosphorylation. Other divalent cations, such as magnesium, zinc, nickel, and cobalt, but not the trivalent cation lanthanum, induced p62 phosphorylation to a similar extent as calcium. There was no close correlation between the ability of the various ions to induce p62 phosphorylation and increase free intracellular calcium. Similarly, treatment of primary keratinocytes with the calcium ionophores A23187 or X537A did not induce p62 phosphorylation, although it increased free intracellular calcium levels. Finally, blockers of potassium uptake, which is induced by calcium, did not inhibit p62 phosphorylation. Thus, in keratinocyte differentiation, calcium is likely to provide the primary signal for p62 tyrosine phosphorylation and may act directly at the cell membrane through a "cationic receptor mechanism" analogous to that described in other cell types.

Animals↗
PubMed1994

Leg-crossing: incidence and inheritance.

Leg-crossing refers to the preferential tendency for individuals to sit with one leg crossed over the other. In this study about 62% of the population are right leg-crossers, 26% are left leg-crossers, and the remaining 12% report that they have no preference or are indifferent. Familial data suggest that leg-crossing may be under genetic control: although the data do not fit any straightforward recessive or dominant Mendelian model, they are compatible with the type of model invoking fluctuating asymmetry which has been used to explain the inheritance of handedness, hand-clasping and arm-folding.

Adult↗
PubMed1994

Restoration of differentiation and suppression of tumorigenicity in somatic cell hybrids of human squamous carcinoma cells and keratinocytes.

Somatic cell hybrid cell lines derived from the fusion of human squamous carcinoma cells (FaDu-Hyg) with human keratinocytes were used to examine the relationships between cell differentiation and tumorigenicity. Treatment of the parental keratinocytes or the two hybrid cell lines with the combination of calcium and fetal bovine serum increased the expression of the envelope precursor, involucrin, 4- to 8-fold, whereas it remained unchanged in FaDu-Hyg cells. Similarly, calcium- and serum-treated keratinocytes and the two hybrid cell lines displayed a 7- to 13-fold increase of the activity of membrane-associated type I transglutaminase, whereas transglutaminase activity in FaDu-Hyg cells did not change appreciably. FaDu-Hyg cells were tumorigenic in vivo, but tumorigenicity was suppressed in both hybrid cell lines. Analysis of additional tumor cell lines indicated that the expression of transglutaminase I and involucrin are under separate genetic control and that loss of transglutaminase activity can result either from a lack of protein or from a defect in the activation step. Thus, keratinization of squamous epithelial cells appears to be controlled by several different recessive genes, which cosegregate with but are probably only partly identical with the genes that suppress tumor formation in vivo.

Animals↗
PubMed1993

Resistance of human squamous carcinoma cells to transforming growth factor beta 1 is a recessive trait.

Because most human squamous carcinoma cell lines of the aerodigestive and genital tracts are refractory to the antiproliferative action of transforming growth factor beta 1 (TGF beta 1) in vitro, we have begun to identify the causes for resistance of squamous carcinoma cell lines to TGF beta 1 by using somatic cell genetics. Two stable hybrid cell lines (FaDu-HKc.1 and FaDu-HKc.2) were obtained by fusing a TGF beta 1-resistant human squamous carcinoma cell line, FaDu-HygR, with a human papilloma virus 16-immortalized, TGF beta 1-sensitive, human foreskin keratinocyte cell line, HKc-neoR. Whereas TGF beta 1 did not inhibit DNA synthesis in parental FaDu-HygR cells, it reduced DNA synthetic activity of HKc-neoR, FaDu-HKc.1, and FaDu-HKc.2 cells by 75-85% (IC50, 2-5 pM). Although squamous carcinoma cells express lower than normal levels of TGF beta 1 type II receptors on their cell surface, TGF beta 1 type II receptor mRNA was detected in all four cell lines. Recessive genes involved in TGF beta 1 signaling may be localized to the distal portion of chromosome 18q, as this was the sole chromosomal region of homozygous deletion in parental FaDu-HygR cells. Furthermore, our previous observation that mutant p53 decreases sensitivity of keratinocytes to TGF beta 1 was supported by the finding that the level of the mutant p53 protein expressed by the hybrid cell lines was greatly reduced. In summary, TGF beta 1 resistance of FaDu cells appears to be recessive and is presumably due to the loss of one or more post-receptor elements of the signaling pathway.

Base Sequence↗
PubMed1993

Mutant p53 tumor suppressor gene causes resistance to transforming growth factor beta 1 in murine keratinocytes.

Human carcinoma cell lines are frequently refractory to the antiproliferative effect of the autocrine growth inhibitor transforming growth factor beta 1 (TGF-beta 1) and often express mutant forms of the tumor suppressor gene p53. Therefore, we wished to determine whether mutant p53 affects the cellular response to TGF-beta 1. A murine p53 complementary DNA carrying an activating point mutation was introduced into TGF-beta 1-sensitive BALB/MK mouse epidermal keratinocytes by retroviral infection. Mp53 transformed cells displayed a spindle-type morphology and expressed between 0.02 and 0.7 ng of mutant p53/mg total protein. Furthermore, whereas TGF-beta 1 caused approximately 90% maximal inhibition of DNA synthesis of parental BALB/MK cells, the Mp53 transformants were inhibited by less than 70%. The median inhibiting dose of TGF-beta 1 was 4.07 +/- 1 (SE) pM for BALB/MK cells, but ranged from 2.4 to 11.2 pM and from 11.7 to 40 pM for two different sets of Mp53 transformants, and increased as a function of the amounts of mutant p53 protein that were expressed. Our findings suggest that mutant forms of p53 inhibit the antiproliferative effect of TGF-beta 1 by interfering with its signaling pathway.

Animals↗
PubMed1993

Terfenadine (Seldane): a new drug for restoring sensitivity to multidrug resistant cancer cells.

In our efforts to identify clinically effective drugs for reversing multidrug resistance (MDR) mediated by P-glycoprotein, we tested terfenadine for anti-MDR activity because it appeared to sensitize a patient to doxorubicin and because it met structural requirements defined for this activity. Terfenadine sensitized MCF-7/ADR human breast cancer cells and L1210/VMDRC.06 murine leukemia cells to doxorubicin. At concentrations < or = 10 microM, terfenadine decreased the IC50 to doxorubicin by up to 25-fold against MCF-7/ADR cells and completely restored sensitivity to L1210/VMDRC.06 cells. The drug had no effect on the sensitive, parental cell lines and enhanced activity of other drugs affected by the MDR phenotype. Terfenadine was as potent as trans-flupenthixol, one of the most active modulators of MDR. The mechanism of action of terfenadine appeared to be due to inhibition of the function of P-glycoprotein since it augmented the accumulation of doxorubicin and inhibited the efflux of rhodamine 123 from MDR lines but had no effect on drug accumulation or efflux in sensitive cells. Terfenadine displaced azidopine from P-glycoprotein, but at concentrations higher than expected based on its overall potency. Since terfenadine is clinically available, has numerous structural derivatives available for study, and has a relatively low toxicity profile, this drug and drugs of its class should be evaluated for future clinical trials.

ATP Binding Cassette Transporter, Subfamily B, Mem↗