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P H Schmidt

Publications and source records attributed to P H Schmidt.

At least 19 recordsLinked to original sources

AKAP350, a multiply spliced protein kinase A-anchoring protein associated with centrosomes.

Protein kinase A-anchoring proteins (AKAPs) localize the second messenger response to particular subcellular domains by sequestration of the type II protein kinase A. Previously, AKAP120 was identified from a rabbit gastric parietal cell cDNA library; however, a monoclonal antibody raised against AKAP120 labeled a 350-kDa band in Western blots of parietal cell cytosol. Recloning has now revealed that AKAP120 is a segment of a larger protein, AKAP350. We have now obtained a complete sequence of human gastric AKAP350 as well as partial cDNA sequences from human lung and rabbit parietal cells. The genomic region containing AKAP350 is found on chromosome 7q21 and is multiply spliced, producing at least three distinct AKAP350 isoforms as well as yotiao, a protein associated with the N-methyl-D-aspartate receptor. Rabbit parietal cell AKAP350 is missing a sequence corresponding to a single exon in the middle of the molecule located just after the yotiao homology region. Two carboxyl-terminal splice variants were also identified. Both of the major splice variants showed tissue- and cell-specific expression patterns. Immunofluorescence microscopy demonstrated that AKAP350 was associated with centrosomes in many cell types. In polarized Madin-Darby canine kidney cells, AKAP350 localized asymmetrically to one pole of the centrosome, and nocodazole did not alter its localization. During the cell cycle, AKAP350 was associated with the centrosomes as well as with the cleavage furrow during anaphase and telophase. Several epithelial cell types also demonstrated noncentrosomal pools of AKAP350, especially parietal cells, which contained multiple cytosolic immunoreactive foci throughout the cells. The localization of AKAP350 suggests that it may regulate centrosomal and noncentrosomal cytoskeletal systems in many different cell types.

A Kinase Anchor Proteins

Membrane potassium channels and human bladder tumor cells. I. Electrical properties.

These experiments were conducted to determine the membrane K+ currents and channels in human urinary bladder (HTB-9) carcinoma cells in vitro. K+ currents and channel activity were assessed by the whole-cell voltage clamp and by either inside-out or outside-out patch clamp recordings. Cell depolarization resulted in activation of a Ca(2+)-dependent outward K+ current, 0.57 +/- 0.13 nS/pF at -70 mV holding potential and 3.10 +/- 0.15 nS/pF at 30 mV holding potential. Corresponding patch clamp measurements demonstrated a Ca(2+)-activated, voltage-dependent K+ channel (KCa) of 214 +/- 3.0 pS. Scorpion venom peptides, charybdotoxin (ChTx) and iberiotoxin (IbTx), inhibited both the activated current and the KCa activity. In addition, on-cell patch recordings demonstrated an inwardly rectifying K+ channel, 21 +/- 1 pS at positive transmembrane potential (Vm) and 145 +/- 13 pS at negative Vm. Glibenclamide (50 microM), Ba2+ (1 mM) and quinine (100 microM) each inhibited the corresponding nonactivated, basal whole-cell current. Moreover, glibenclamide inhibited K+ channels in inside/out patches in a dose-dependent manner, and the IC50 = 46 microM. The identity of this K+ channel with an ATP-sensitive K+ channel (KATP) was confirmed by its inhibition with ATP (2 mM) and by its activation with diazoxide (100 microM). We conclude that plasma membranes of HTB-9 cells contain the KCa and a lower conductance K+ channel with properties consistent with a sulfonylurea receptor-linked KATP.

Cell Membrane

Does intervention improve the natural course of glomus tumors? A series of 108 patients seen in a 32-year period.

To acquire more insight into the results of treatment versus the "natural" course of glomus tumors, we studied the clinical data of 108 patients, in 58 of whom the disease was hereditary. During a period of 32 years (1956 to 1988), 175 tumors were diagnosed: 52 glomus jugulotympanic tumors, 32 vagal body tumors, and 91 carotid body tumors. The results of radical surgical treatment were disappointing for tumors located at the skull base, ie, nonradical in 59% (n = 23) of the cases, but very good for the carotid body tumors, for which 96% (n = 68) radical excision was achieved. Moreover, surgery at the level of the skull base dramatically increased morbidity, since it frequently induced cranial nerve palsy. During the follow-up period (maximal observation time 32 years, mean 13.5 years) none of the patients died of residual or recurrent tumor or developed distant metastases, irrespective of the mode and outcome of treatment. When these results are combined with the results of pedigree analysis, a realistic approximation of the "natural" course of the disease for both hereditary and nonfamilial tumors can be made. The results raise the question of whether this natural behavior is really improved by intervention. We conclude that removal of carotid body tumors and solitary vagal body tumors should be considered in order to prevent future morbidity. However, for skull base and bilateral glomus tumors a more conservative monitored "wait and see" policy can be sensible and should be considered in any proposal for treatment of head and neck paragangliomas.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

DNA flow cytometry of hereditary and sporadic paragangliomas (glomus tumours).

Paragangliomas (glomus tumours) are benign, hypervascular tumours which in general are treated by surgical excision. The indication for treatment of these often slow-growing tumours needs additional criteria for predicting tumour progressiveness. For this reason the nuclear DNA content of 99 paragangliomas, 65 of them originating from patients with a positive family history, was analysed by flow cytometry. Unequivocal evidence of DNA aneuploidy was found in 37% of these clinically and histologically benign tumours, the average duration of follow up amounting to at least 10 years. The DNA index of the aneuploid tumours ranged from 0.90 to 2.03. No correlation was found between DNA ploidy and familiality or between DNA content and clinical criteria indicative of tumour progression, which means that DNA ploidy of these tumours cannot serve as a predictor for an expected growth pattern or familiality. DNA aneuploidy in hereditary and sporadic paragangliomas is not clinically related to malignancy, but indicates that these tumours are true neoplasias cytogenetically.

DNA, Neoplasm

A longitudinal electrocochleographic study of a case of long-standing bilateral Lermoyez's syndrome.

An 18-year follow-up of a case of bilateral Lermoyez's syndrome is presented. The left ear having reached a stabilized hearing loss about 9 years after the onset of the disease, the right ear, apart from some isolated early periods of hearing loss, started to show the full extent of clinical symptoms after about 16 years. Electrocochleographic observations are presented. Studies were performed twice in the right ear during a period of strongly fluctuating hearing thresholds, once in an impaired and once in a relatively good condition. Electrocochleography of the stabilized left ear was performed as well. The data are compared with electrocochleographical observations in the left ear in its early fluctuating stage. Variation of cochlear physiological data during the fluctuating stage of the disease shows remarkable correspondence between the two ears. The stabilized Lermoyez ear is shown to have developed considerable hair cell loss, but may still have preserved its endolymphatic hydrops. These findings in Lermoyez's syndrome fit well into the observations reported in patients with Menière's disease.

Audiometry, Evoked Response

Genomic imprinting in hereditary glomus tumours: evidence for new genetic theory.

A study based on fifteen pedigrees showed that familial glomus tumours are inherited almost exclusively via the paternal line, a finding inconsistent with autosomal dominant transmission. The results can be explained in terms of the genomic imprinting hypothesis--the maternally derived gene is inactivated during female oogenesis and can be reactivated only during spermatogenesis. Genomic imprinting may have considerable implications for genetic counselling with respect to glomus tumours and also for the understanding of other hereditary diseases.

Adolescent

Sequential administration of human and porcine factor VIII for surgical treatment of a parotid tumour in a patient with a factor VIII inhibitor.

The sequential use of human and porcine factor VIII for the treatment of a patient with a moderately high titre (38 Bethesda units) factor VIII inhibitor enabled us to provide adequate haemostatic cover for 17 days. In this period a pleomorphic adenoma of the parotid gland was removed. Bleeding did not occur and wound healing was uneventful.

Adenoma, Pleomorphic

Electrocochleographic diagnosis.

The most characteristic electrocochleografic features of Menière's disease are a broad waveform, steep input-output curves, normal amplitude-latency relations and large summating potentials. The electrocochleografic data obtained in an individual case can be compared with the parameters of a reference set composed of a great number of patients with a well established diagnosis. For a new diagnostic case this leads with the aid of statistical methods and computer assistance to a probability diagnosis.

Action Potentials